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  • 251.
    Krachler, Benno
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Reported food intake and distribution of body fat: a repeated cross-sectional study2006In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 22, no 5, p. 34-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Body mass, as well as distribution of body fat, are predictors of both diabetes and cardiovascular disease. In Northern Sweden, despite a marked increase in average body mass, prevalence of diabetes was stagnant and myocardial infarctions decreased. A more favourable distribution of body fat is a possible contributing factor.This study investigates the relative importance of individual food items for time trends in waist circumference (WC) and hip circumference (HC) on a population level. METHODS: Independent cross-sectional surveys conducted in 1986, 1990, 1994 and 1999 in the two northernmost counties of Sweden with a common population of 250,000. Randomly selected age stratified samples, altogether 2982 men and 3087 women aged 25-64 years. Questionnaires were completed and anthropometric measurements taken. For each food item, associations between frequency of consumption and waist and hip circumferences were estimated. Partial regression coefficients for every level of reported intake were multiplied with differences in proportion of the population reporting the corresponding levels of intake in 1986 and 1999. The sum of these product terms for every food item was the respective estimated impact on mean circumference. RESULTS: Time trends in reported food consumption associated with the more favourable gynoid distribution of adipose tissue were increased use of vegetable oil, pasta and 1.5% fat milk. Trends associated with abdominal obesity were increased consumption of beer in men and higher intake of hamburgers and French fried potatoes in women. CONCLUSION: Food trends as markers of time trends in body fat distribution have been identified. The method is a complement to conventional approaches to establish associations between food intake and disease risk on a population level.

  • 252. Kraft, Peter
    et al.
    Pharoah, Paul
    Chanock, Stephen J
    Albanes, Demetrius
    Kolonel, Laurence N
    Hayes, Richard B
    Altshuler, David
    Andriole, Gerald
    Berg, Christine
    Boeing, Heiner
    Burtt, Noel P
    Bueno-de-Mesquita, Bas
    Calle, Eugenia E
    Cann, Howard
    Canzian, Federico
    Chen, Yen-Ching
    Crawford, David E
    Dunning, Alison M
    Feigelson, Heather S
    Freedman, Matthew L
    Gaziano, John M
    Giovannucci, Ed
    Gonzalez, Carlos Alberto
    Haiman, Christopher A
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henderson, Brian E
    Hirschhorn, Joel N
    Hunter, David J
    Kaaks, Rudolf
    Key, Timothy
    Le Marchand, Loic
    Ma, Jing
    Overvad, Kim
    Palli, Domenico
    Pike, Malcolm C
    Riboli, Elio
    Rodriguez, Carmen
    Setiawan, Wendy V
    Stampfer, Meir J
    Stram, Daniel O
    Thomas, Gilles
    Thun, Michael J
    Travis, Ruth
    Trichopoulou, Antonia
    Virtamo, Jarmo
    Wacholder, Sholom
    Genetic variation in the HSD17B1 gene and risk of prostate cancer.2005In: PLoS Genet, ISSN 1553-7404, Vol. 1, no 5, p. e68-Article in journal (Refereed)
  • 253. Kraja, Aldi T.
    et al.
    Cook, James P.
    Warren, Helen R.
    Surendran, Praveen
    Liu, Chunyu
    Evangelou, Evangelos
    Manning, Alisa K.
    Grarup, Niels
    Drenos, Fotios
    Sim, Xueling
    Smith, Albert Vernon
    Amin, Najaf
    Blakemore, Alexandra I. F.
    Bork-Jensen, Jette
    Brandslund, Ivan
    Farmaki, Aliki-Eleni
    Fava, Cristiano
    Ferreira, Teresa
    Herzig, Karl-Heinz
    Giri, Ayush
    Giulianini, Franco
    Grove, Megan L.
    Guo, Xiuqing
    Harris, Sarah E.
    Have, Christian T.
    Havulinna, Aki S.
    Zhang, He
    Jorgensen, Marit E.
    Karajamaki, AnneMari
    Kooperberg, Charles
    Linneberg, Allan
    Little, Louis
    Liu, Yongmei
    Bonnycastle, Lori L.
    Lu, Yingchang
    Magi, Reedik
    Mahajan, Anubha
    Malerba, Giovanni
    Marioni, Riccardo E.
    Mei, Hao
    Menni, Cristina
    Morrison, Alanna C.
    Padmanabhan, Sandosh
    Palmas, Walter
    Poveda, Alaitz
    Rauramaa, Rainer
    Rayner, Nigel William
    Riaz, Muhammad
    Rice, Ken
    Richard, Melissa A.
    Smith, Jennifer A.
    Southam, Lorraine
    Stancakova, Alena
    Stirrups, Kathleen E.
    Tragante, Vinicius
    Tuomi, Tiinamaija
    Umeå University, Faculty of Medicine, Department of Biobank Research. Folkhälsan Research Centre, Finland; Department of Endocrinology, Helsinki University Central Hospital, Finland; Finnish Institute for Molecular Medicine (FIMM), Helsinki University, Finland.
    Tzoulald, Ioanna
    Varga, Tibor V.
    Weiss, Stefan
    Yiorkas, Andrianos M.
    Young, Robin
    Zhang, Weihua
    Barnes, Michael R.
    Cabrera, Claudia P.
    Gao, He
    Boehnke, Michael
    Boerwinkle, Eric
    Chambers, John C.
    Connell, John M.
    Christensen, Cramer K.
    de Boer, Rudolf A.
    Deary, Ian J.
    Dedoussis, George
    Deloukas, Panos
    Dominiczak, Anna F.
    Dorr, Marcus
    Joehanes, Roby
    Edwards, Todd L.
    Esko, Tonu
    Fornage, Myriam
    Franceschini, Nora
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
    Gambaro, Giovanni
    Groop, Leif
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hansen, Torben
    Hayward, Caroline
    Heikki, Oksa
    Ingelsson, Erik
    Tuomilehto, Jaakko
    Jarvelin, Marjo-Riitta
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kooner, Jaspal S.
    Lakka, Timo A.
    Langenberg, Claudia
    Lind, Lars
    Loos, Ruth J. F.
    Laakso, Markku
    McCarthy, Mark I.
    Melander, Olle
    Mohlke, Karen L.
    Moris, Andrwe P.
    Palmer, Colin N. A.
    Pedersen, Oluf
    Polasek, Ozren
    Poulter, Neil R.
    Province, Michael A.
    Psaty, Bruce M.
    Ridker, Paul M.
    Rotter, Jerome I.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Sever, Peter J.
    Skaaby, Tea
    Stafford, Jeanette M.
    Starr, John M.
    van der Harst, Pim
    van der Meer, Peter
    van Duijn, Cornelia M.
    Vergnaud, Anne-Claire
    Gudnason, Vilmundur
    Wareham, Nicholas J.
    Wilson, James G.
    Willer, Cristen J.
    Witte, Daniel R.
    Zeggini, Eleftheria
    Saleheen, Danish
    Butterworth, Adam S.
    Danesh, John
    Asselbergs, Folkert W.
    Wain, Louise V.
    Ehret, Georg B.
    Chasman, Daniel I.
    Caulfield, Mark J.
    Elliott, Paul
    Lindgren, Cecilia M.
    Levy, Daniel
    Newton-Cheh, Christopher
    Munroe, Patricia B.
    Howson, Joanna M. M.
    New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals2017In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 10, no 5, article id e001778Article in journal (Refereed)
    Abstract [en]

    Background-Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. & para;& para;Methods and Results-Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.& para;& para;Conclusions-We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.

  • 254. Kreimer, Aimée R
    et al.
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    Waterboer, Tim
    Kaaks, Rudolf
    Chang-Claude, Jenny
    Drogen, Dagmar
    Tjønneland, Anne
    Overvad, Kim
    Quirós, J Ramón
    González, Carlos A
    Sánchez, Maria José
    Larrañaga, Nerea
    Navarro, Carmen
    Barricarte, Aurelio
    Travis, Ruth C
    Khaw, Kay-Tee
    Wareham, Nick
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Peeters, Petra H M
    Panico, Salvatore
    Masala, Giovanna
    Grioni, Sara
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, H Bas
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Manjer, Jonas
    Ekström, Johanna
    Skeie, Guri
    Lund, Eiliv
    Weiderpass, Elisabete
    Ferrari, Pietro
    Byrnes, Graham
    Romieu, Isabelle
    Riboli, Elio
    Hildesheim, Allan
    Boeing, Heiner
    Pawlita, Michael
    Brennan, Paul
    Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer2013In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 31, no 21, p. 2708-2715Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.

    METHODS: We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.

    RESULTS: HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.

    CONCLUSION: HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.

  • 255. Kurbasic, Azra
    et al.
    Fraser, Abigail
    Mogren, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Clinical Sciences Malmö, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Clinical Sciences Malmö, Lund University, Malmö, Sweden. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA..
    Rich-Edwards, Janet W.
    Timpka, Simon
    Maternal Hypertensive Disorders of Pregnancy and Offspring Risk of Hypertension: A Population-Based Cohort and Sibling Study2019In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 32, no 4, p. 331-334Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased risk of hypertension, cardiovascular disease, and type 2 diabetes. Offspring from pregnancies complicated by HDP also have worse cardiometabolic status in childhood and young adulthood, but the offspring risk of clinical hypertension in adulthood is largely unknown.

    METHODS: We studied 13,893 first-born adult offspring (49.4% female) who attended a structured population-based primary care visit (The Västerbotten Health Survey) at age 40 years in Sweden between 1994 and 2013. Data on maternal HDP were collected from a population-based birth register. We investigated the association between maternal HDP and the risk of adult offspring hypertension and worse cardiometabolic risk factor status utilizing multivariable poisson and linear regression models. We also conducted a sibling comparison, which inherently accounted for familial factors shared by siblings (N = 135).

    RESULTS: Offspring participants of women with HDP (N = 383, 2.8%) had increased relative risk of hypertension (1.67, 95% confidence interval: 1.38, 2.01) and also higher mean body mass index, systolic blood pressure, diastolic blood pressure, and worse 2-hour 75 g oral glucose tolerance test result at age 40 years. No difference was observed for serum cholesterol. Point estimates for the cardiometabolic risk factors were attenuated in the sibling analyses.

    CONCLUSION: Offspring born to mothers with a history of HDP are on an adverse cardiometabolic trajectory and should be considered as concomitant targets for primordial prevention of hypertension in the maternal post-pregnancy period.

  • 256. Kurbasic, Azra
    et al.
    Poveda, Alaitz
    Chen, Yan
    Ågren, Åsa
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Engberg, Elisabeth
    Umeå University, Faculty of Social Sciences, Demographic Data Base.
    Hu, Frank B
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Barroso, Ines
    Brändström, Anders
    Umeå University, Faculty of Social Sciences, Demographic Data Base.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies2014In: Current nutrition reports, ISSN 2161-3311, Vol. 3, no 4, p. 400-411Article in journal (Refereed)
    Abstract [en]

    Most complex diseases have well-established genetic and non-genetic risk factors. In some instances, these risk factors are likely to interact, whereby their joint effects convey a level of risk that is either significantly more or less than the sum of these risks. Characterizing these gene-environment interactions may help elucidate the biology of complex diseases, as well as to guide strategies for their targeted prevention. In most cases, the detection of gene-environment interactions will require sample sizes in excess of those needed to detect the marginal effects of the genetic and environmental risk factors. Although many consortia have been formed, comprising multiple diverse cohorts to detect gene-environment interactions, few robust examples of such interactions have been discovered. This may be because combining data across studies, usually through meta-analysis of summary data from the contributing cohorts, is often a statistically inefficient approach for the detection of gene-environment interactions. Ideally, single, very large and well-genotyped prospective cohorts, with validated measures of environmental risk factor and disease outcomes should be used to study interactions. The presence of strong founder effects within those cohorts might further strengthen the capacity to detect novel genetic effects and gene-environment interactions. Access to accurate genealogical data would also aid in studying the diploid nature of the human genome, such as genomic imprinting (parent-of-origin effects). Here we describe two studies from northern Sweden (the GLACIER and VIKING studies) that fulfill these characteristics.

  • 257. Kyro, Cecilie
    et al.
    Skeie, Guri
    Dragsted, Lars O.
    Christensen, Jane
    Overvad, Kim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lund, Eiliv
    Slimani, Nadia
    Johnsen, Nina F.
    Halkjaer, Jytte
    Tjonneland, Anne
    Olsen, Anja
    Intake of whole grain in Scandinavia: Intake, sources and compliance with new national recommendations2012In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 40, no 1, p. 76-84Article in journal (Refereed)
    Abstract [en]

    Aims: The aim of the present study was to describe the intake of whole grain (WG) in Norway, Sweden and Denmark, and to investigate what proportion of the study population that met the new WG recommendation (75 g WG/day per 10 MJ).

    Methods: Descriptive study. Data is from one 24h dietary recall (24HDR) collected in 1995-2000 from a subset (n = 8,702) of the large Scandinavian cohort "HELGA" consisting of participants aged 30-65 years from three cohorts.

    Results: The mean WG intake was far below the recommended level. Between 16% (Danish men) and 35% (Norwegian women) consumed at least the recommended intake of WG. Among women, the median intake of WG products (g WG products/day) was 114 g/day in Norway and 108 g/day in Denmark, whereas the intake was much lower in Sweden (64 g/day). For women, the median intake of WG in absolute amounts (g WG/day) was again highest in Norway (44 g/day), but lower in both Sweden (35 g/day) and Denmark (31 g/day). For men (no data available for Norwegian men), the intake of WG products was higher in Denmark (138 g/day) compared to Sweden (79 g/day), but when looking at the WG intake in absolute amounts, the intake was highest in Sweden (49 g/day) compared to Denmark (41 g/day).

    Conclusions: The present study described the intake of WG as well as the sources of WG in Norway, Sweden and Denmark. Between 16% and 35% met the new recommendations on intake of WG.

  • 258. Kyrø, Cecilie
    et al.
    Skeie, Guri
    Dragsted, Lars O
    Christensen, Jane
    Overvad, Kim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Lund, Eiliv
    Slimani, Nadia
    Johnsen, Nina F
    Halkjær, Jytte
    Tjønneland, Anne
    Olsen, Anja
    Intake of whole grains in Scandinavia is associated with healthy lifestyle, socio-economic and dietary factors2011In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 14, no 10, p. 1787-1795Article in journal (Refereed)
    Abstract [en]

    Objective: To identify the dietary, lifestyle and socio-economic factors associated with the intake of whole grains (WG) in Norway, Sweden and Denmark.

    Design: A cross-sectional study.

    Setting: Subsample of the Scandinavian cohort ‘HELGA’ consisting of three prospective cohorts: The Norwegian Women and Cancer Study; The Northern Sweden Health and Disease Study; and the Danish Diet, Cancer and Health Study.

    Subjects: A total of 8702 men and women aged 30–65 years. Dietary data are from one 24 h dietary recall and data on socio-economic status and lifestyle factors including anthropometric values are from the baseline collection of data.

    Results: Vegetables, fruits, dairy products, fish and shellfish, coffee, tea and margarine were directly associated with the intake of WG, whereas red meat, white bread, alcohol and cakes and biscuits were inversely associated. Smoking and BMI were consistently inversely associated with the intake of WG. Furthermore, length of education was directly associated with the intake of WG among women.

    Conclusions: The intake of WG was found to be directly associated with healthy diet, lifestyle and socio-economic factors and inversely associated with less healthy factors, suggesting that these factors are important for consideration as potential confounders when studying WG intake and disease associations.

  • 259. Lahmann, Petra H
    et al.
    Hoffmann, Kurt
    Allen, Naomi
    van Gils, Carla H
    Khaw, Kay-Tee
    Tehard, Bertrand
    Berrino, Franco
    Tjønneland, Anne
    Bigaard, Janne
    Olsen, Anja
    Overvad, Kim
    Clavel-Chapelon, Françoise
    Nagel, Gabriele
    Boeing, Heiner
    Trichopoulos, Dimitrios
    Economou, George
    Bellos, George
    Palli, Domenico
    Tumino, Rosario
    Panico, Salvatore
    Sacerdote, Carlotta
    Krogh, Vittorio
    Peeters, Petra H M
    Bueno-de-Mesquita, H Bas
    Lund, Eiliv
    Ardanaz, Eva
    Amiano, Pilar
    Pera, Guillem
    Quirós, José R
    Martínez, Carmen
    Tormo, María J
    Wirfält, Elisabet
    Berglund, Göran
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Key, Timothy J
    Reeves, Gillian
    Bingham, Sheila
    Norat, Teresa
    Biessy, Carine
    Kaaks, Rudolf
    Riboli, Elio
    Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC).2004In: International Journal of Cancer, ISSN 0020-7136, Vol. 111, no 5, p. 762-71Article in journal (Refereed)
  • 260. Landberg, R.
    et al.
    Aman, P.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Long-term reproducibility of plasma alkylresorcinols as biomarkers of whole-grain wheat and rye intake within Northern Sweden Health and Disease Study Cohort2013In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 67, no 3, p. 259-263Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OJBECTIVES: Alkylresorcinols (AR) have been suggested as specific biomarkers of whole-grain (WG) and bran intake from wheat and rye. Before using plasma AR as biomarkers in prospective cohort studies, the long-term reproducibility needs to be determined in order to judge how well a single plasma sample reflects the long-term concentration. The objective was therefore to estimate the reproducibility of plasma AR concentrations over 0.1-3.9 years. SUBJECTS/METHODS:The concentrations of AR homologues were analysed in plasma samples, drawn >8 h since last meal, 0.1-3.9 years apart (mean similar to 2 years) in 74 participants in the Swedish prospective Vasterbotten Intervention Project cohort. Reproducibility was estimated by calculating the intra class correlation coefficient (ICC). RESULTS: Fasting plasma AR concentrations were similar between the first and second measurements. The ICC for total AR was 0.54 (95% confidence interval (CI) = 0.38-0.69] overall, 0.34 (95% CI = 0.13-0.64) for men and 0.73 (95% CI = 0.56-0.85) for women, respectively. Somewhat higher ICCs were obtained for shorter AR homologues. CONCLUSION: In summary, the reproducibility of plasma AR over 0.1-3.9 years was high for women and moderate for men within this population. Together with previous data showing high validity of plasma AR as biomarkers of wheat and rye in different populations, the current finding suggest that this biomarker is stable over a long-time period and is therefore probably useful for assessment of long-term WG intake in populations with a wide intake range and a frequent intake.

  • 261. Landberg, Rikard
    et al.
    Andersson, Swen-Olof
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Jan-Erik
    Stenman, Ulf-Håkan
    Adlercreutz, Herman
    Kamal-Eldin, Afaf
    Aman, Per
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rye whole grain and bran intake compared with refined wheat decreases urinary C-peptide, plasma insulin, and prostate specific antigen in men with prostate cancer2010In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 140, no 12, p. 2180-2186Article in journal (Refereed)
    Abstract [en]

    Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to ~50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P = 0.04). Additionally, fasting plasma insulin and 24-h urinary C-peptide excretion were lower after treatment with RP compared with WP (P < 0.01 and P = 0.01, respectively). Daily excretion of 5 lignans was higher after the RP treatment than after the WP treatment (P < 0.001). We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.

  • 262. Langenberg, C.
    et al.
    Sharp, S.
    Forouhi, N. G.
    Franks, Paul
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Schulze, M. B.
    Kerrison, N.
    Ekelund, U.
    Barroso, I.
    Panico, S.
    Tormo, M. J.
    Spranger, J.
    Griffin, S.
    van der Schouw, Y. T.
    Amiano, P.
    Ardanaz, E.
    Arriola, L.
    Balkau, B.
    Barricarte, A.
    Beulens, J. W. J.
    Boeing, H.
    Bueno-de-Mesquita, H. B.
    Buijsse, B.
    Chirlaque Lopez, M. D.
    Clavel-Chapelon, F.
    Crowe, F. L.
    de Lauzon-Guillan, B.
    Deloukas, P.
    Dorronsoro, M.
    Drogan, D.
    Froguel, P.
    Gonzalez, C.
    Grioni, S.
    Groop, L.
    Groves, C.
    Hainaut, P.
    Halkjaer, J.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hansen, T.
    Huerta Castano, J. M.
    Kaaks, R.
    Key, T. J.
    Khaw, K. T.
    Koulman, A.
    Mattiello, A.
    Navarro, C.
    Nilsson, P.
    Norat, T.
    Overvad, K.
    Palla, L.
    Palli, D.
    Pedersen, O.
    Peeters, P. H.
    Quiros, J. R.
    Ramachandran, A.
    Rodriguez-Suarez, L.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Romaguera, D.
    Romieu, I.
    Sacerdote, C.
    Sanchez, M. J.
    Sandbaek, A.
    Slimani, N.
    Sluijs, I.
    Spijkerman, A. M. W.
    Teucher, B.
    Tjonneland, A.
    Tumino, R.
    van der A, D. L.
    Verschuren, W. M. M.
    Tuomilehto, J.
    Feskens, E.
    McCarthy, M.
    Riboli, E.
    Wareham, N. J.
    Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study2011In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, no 9, p. 2272-2282Article in journal (Refereed)
    Abstract [en]

    Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.

  • 263. Langenberg, Claudia
    et al.
    Sharp, Stephen J.
    Schulze, Matthias B
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Overvad, Kim
    Forouhi, Nita G
    Spranger, Joachim
    Drogan, Dagmar
    Maria Huerta, Jose
    Arriola, Larraitz
    de Lauzon-Guillan, Blandine
    Tormo, Maria-Jose
    Ardanaz, Eva
    Balkau, Beverley
    Beulens, Joline WJ
    Boeing, Heiner
    Bueno-de-Mesquita, H Bas
    Clavel-Chapelon, Francoise
    Crowe, Francesca L
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gonzalez, Carlos A
    Grioni, Sara
    Halkjaer, Jytte
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Kaaks, Rudolf
    Kerrison, Nicola D
    Key, Timothy J
    Khaw, Kay Tee
    Mattiello, Amalia
    Nilsson, Peter
    Norat, Teresa
    Palla, Luigi
    Palli, Domenico
    Panico, Salvatore
    Ramon Quiros, J
    Romaguera, Dora
    Romieu, Isabelle
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Sluijs, Ivonne
    Spijkerman, Annemieke MW
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    Daphne, L van der A
    van der Schouw, Yvonne T
    Feskens, Edith JM
    Riboli, Elio
    Wareham, Nicholas J
    Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-interact case-cohort study2012In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 9, no 6, p. e1001230-Article in journal (Refereed)
    Abstract [en]

    Background: Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI).

    Methods and Findings: The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (< 94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI >= 35 kg/m(2)) and a high WC (> 102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women).

    Conclusions: WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.

  • 264. Larsson, B
    et al.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Ericson, T
    Relationship between dental caries and risk factors for atherosclerosis in Swedish adolescents?1995In: Community Dentistry and Oral Epidemiology, ISSN 0301-5661, E-ISSN 1600-0528, Vol. 23, no 4, p. 205-210Article in journal (Refereed)
    Abstract [en]

    In an earlier study on a selected group of adolescents with high caries prevalence we found dietary habits that resembled those considered to promote the development of atherosclerosis. In the present study we have compared DMF-score with factors traditionally associated with the risk for development cardiovascular diseases (CVD). All 15-yr-olds living in an urban community in Northern Sweden 1987-1989 were included. Medical variables related to the risk of developing CVD were evaluated in groups of adolescents with various levels of manifest caries expressed as decayed and filled surfaces (DFS). The proportion of individuals with no medical risk factor at an unfavorable level was significantly higher in a caries free than in a high-caries (DFS > or = 9) group. Adolescents with two or more medical factors reaching unfavorable levels had a significantly higher caries score than the group with no factor at unfavorable level. A significant positive correlation was found for the whole group between DFS-score and relative body weight (body mass index) in an univariate correlation test as well as multiple linear regression analysis. The hypothesis that high caries score can be an indicator for unfavorable levels of traditional risk factors for CVD is not contradicted by the results in the present study but supported by the observed covariation with BMI. We therefore suggest that dietary counseling to adolescents with a high caries score in combination with a moderate obesity can be of advantage in reducing the caries risk as well as the risk for development of CVD at higher ages.

  • 265.
    Larsson, B
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Ericson, T
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Cardiovascular disease risk factors and dental caries in adolescents: effect of a preventive program in Northern Sweden (the Norsjö project).1997In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 86, no 1, p. 63-71Article in journal (Refereed)
    Abstract [en]

    Since 1985 a 10 year prevention programme aiming to reduce cardiovascular diseases (CVD) has been running in the county of Västerbotten in Northern Sweden. The project started in Norsjö. The present investigation is a study on dietary intake, medical CVD risk factors and dental caries in five cross-sectional groups of 15-year-olds during 5 years (1987-1991) of the "Norsjö project". Most of the measured medical and dietary variables followed a similar trend, i.e. a positive trend during the first 3 years (1987-1989) and in the last 2 years (1990-1991) the averages returned towards baseline values. Dental caries prevalence followed a similar trend. Parental educational level did not have a major influence on diet or medical CVD risk factors, but higher caries scores were noted in adolescents with parents with "low" education compared with adolescents where the parents had higher educational levels. The results from the study also point to the fact that dental caries prevalence together with body mass index may indicate adolescents with CVD risk factors at unfavourable levels. Dietary counselling by dental personnel to adolescents with high caries and moderate obesity can be of advantage in reducing caries risk, as well as risk for development of CVD at higher ages.

  • 266. Leenders, Max
    et al.
    Bhattacharjee, Samsiddhi
    Vineis, Paolo
    Stevens, Victoria
    Bueno-de-Mesquita, H. Bas
    Shu, Xiao-Ou
    Amundadottir, Laufey
    Gross, Myron
    Tobias, Geoffrey S.
    Wactawski-Wende, Jean
    Arslan, Alan A.
    Duell, Eric J.
    Fuchs, Charles S.
    Gallinger, Steven
    Hartge, Patricia
    Hoover, Robert N.
    Holly, Elizabeth A.
    Jacobs, Eric J.
    Klein, Alison P.
    Kooperberg, Charles
    LaCroix, Andrea
    Li, Donghui
    Mandelson, Margaret T.
    Olson, Sara H.
    Petersen, Gloria
    Risch, Harvey A.
    Yu, Kai
    Wolpin, Brian M.
    Zheng, Wei
    Agalliu, Ilir
    Albanes, Demetrius
    Boutron-Ruault, Marie-Christine
    Bracci, Paige M.
    Buring, Julie E.
    Canzian, Federico
    Chang, Kenneth
    Chanock, Stephen J.
    Cotterchio, Michelle
    Gaziano, J. Michael
    Giovanucci, Edward L.
    Goggins, Michael
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hankinson, Susan E.
    Hoffman-Bolton, Judith A.
    Hunter, David J.
    Hutchinson, Amy
    Jacobs, Kevin B.
    Jenab, Mazda
    Khaw, Kay-Tee
    Kraft, Peter
    Krogh, Vittorio
    Kurtz, Robert C.
    McWilliams, Robert R.
    Mendelsohn, Julie B.
    Patel, Alpa V.
    Rabe, Kari G.
    Riboli, Elio
    Tjonneland, Anne
    Trichopoulos, Dimitrios
    Virtamo, Jarmo
    Visvanathan, Kala
    Elena, Joanne W.
    Yu, Herbert
    Zeleniuch-Jacquotte, Anne
    Stolzenberg-Solomon, Rachael Z.
    Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC42013In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 24, no 3, p. 595-602Article in journal (Refereed)
    Abstract [en]

    The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed. Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (< 0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.

  • 267. Lei, Haixin
    et al.
    Hemminki, Kari
    Altieri, Andrea
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Enquist, Kerstin
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Försti, Asta
    Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression.2007In: Breast Cancer Res Treat, ISSN 0167-6806, Vol. 103, no 1, p. 61-69Article in journal (Refereed)
  • 268. Leo, Paul J
    et al.
    Madeleine, Margaret M
    Wang, Sophia
    Schwartz, Stephen M
    Newell, Felicity
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hemminki, Kari
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Tiews, Sven
    Steinberg, Winfried
    Rader, Janet S
    Castro, Felipe
    Safaeian, Mahboobeh
    Franco, Eduardo L
    Coutlée, François
    Ohlsson, Claes
    Cortes, Adrian
    Marshall, Mhairi
    Mukhopadhyay, Pamela
    Cremin, Katie
    Johnson, Lisa G
    Garland, Suzanne
    Tabrizi, Sepehr N
    Wentzensen, Nicolas
    Sitas, Freddy
    Little, Julian
    Cruickshank, Maggie
    Frazer, Ian H
    Hildesheim, Allan
    Brown, Matthew A
    Defining the genetic susceptibility to cervical neoplasia: A genome-wide association study2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 8, article id e1006866Article in journal (Refereed)
    Abstract [en]

    A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

  • 269. Leufkens, Anke M
    et al.
    van Duijnhoven, Fränzel J B
    Boshuizen, Hendriek C
    Siersema, Peter D
    Kunst, Anton E
    Mouw, Traci
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Krogh, Vittorio
    Tumino, Rosario
    Panico, Salvatore
    Polidoro, Silvia
    Palli, Domenico
    Kaaks, Rudolf
    Teucher, Birgit
    Pischon, Tobias
    Trichopoulou, Antonia
    Orfanos, Philippos
    Goufa, Ioulia
    Peeters, Petra H M
    Skeie, Guri
    Braaten, Tonje
    Rodríguez, Laudina
    Lujan-Barroso, Leila
    Sánchez-Pérez, Maria-José
    Navarro, Carmen
    Barricarte, Aurelio
    Zackrisson, Sophia
    Almquist, Martin
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tsilidis, Konstantinos K
    Khaw, Kay-Tee
    Wareham, Nick
    Gallo, Valentina
    Jenab, Mazda
    Riboli, Elio
    Bueno-de-Mesquita, H B
    Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location2011In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 3, p. 622-630Article in journal (Refereed)
    Abstract [en]

    Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57–0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58–0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe.

  • 270. Leufkens, Anke M
    et al.
    Van Duijnhoven, Fränzel J B
    Siersema, Peter D
    Boshuizen, Hendriek C
    Vrieling, Alina
    Agudo, Antonio
    Gram, Inger T
    Weiderpass, Elisabete
    Dahm, Christina
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Palli, Domenico
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Charlotta
    Mattiello, Amalia
    Herman, Silke
    Kaaks, Rudolf
    Steffen, Annika
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Peeters, Petra H
    van Gils, Carla H
    van Kranen, Henk
    Lund, Eliv
    Dumeaux, Vanessa
    Engeset, Dagrun
    Rodríguez, Laudina
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Manjer, Jonas
    Almquist, Martin
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Tsilidis, Konstantinos K
    Straif, Kurt
    Leon-Roux, Maria
    Vineis, Paul
    Norat, Teresa
    Riboli, Elio
    Bueno-de-Mesquita, H Bas
    Cigarette smoking and colorectal cancer risk in the European prospective investigation into cancer and nutrition study2011In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 9, no 2, p. 137-144Article in journal (Refereed)
    Abstract [en]

    Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.

  • 271. Leufkens, Anke M
    et al.
    van Duijnhoven, Fränzel JB
    Woudt, Sjoukje HS
    Siersema, Peter D
    Jenab, Mazda
    Jansen, Eugene HJM
    Pischon, Tobias
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Vineis, Paolo
    Panico, Salvatore
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Dilis, Vardis
    Peeters, Petra H
    Skeie, Guri
    González, Carlos A
    Argüelles, Marcial
    Sánchez, María-José
    Dorronsoro, Miren
    Huerta, José María
    Ardanaz, Eva
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E
    Crowe, Francesca L
    Fedirko, Veronika
    Norat, Teresa
    Riboli, Elio
    Bueno-de-Mesquita, H Bas
    Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation into Cancer and Nutrition2012In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 175, no 7, p. 653-663Article in journal (Refereed)
    Abstract [en]

    Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR(adj)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR(adj) = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.

  • 272. Li, Donghui
    et al.
    Duell, Eric J.
    Yu, Kai
    Risch, Harvey A.
    Olson, Sara H.
    Kooperberg, Charles
    Wolpin, Brian M.
    Jiao, Li
    Dong, Xiaoqun
    Wheeler, Bill
    Arslan, Alan A.
    Bueno-de-Mesquita, H. Bas
    Fuchs, Charles S.
    Gallinger, Steven
    Gross, Myron
    Hartge, Patricia
    Hoover, Robert N.
    Holly, Elizabeth A.
    Jacobs, Eric J.
    Klein, Alison P.
    LaCroix, Andrea
    Mandelson, Margaret T.
    Petersen, Gloria
    Zheng, Wei
    Agalliu, Ilir
    Albanes, Demetrius
    Boutron-Ruault, Marie-Christine
    Bracci, Paige M.
    Buring, Julie E.
    Canzian, Federico
    Chang, Kenneth
    Chanock, Stephen J.
    Cotterchio, Michelle
    Gaziano, J. Michael
    Giovannucci, Edward L.
    Goggins, Michael
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hankinson, Susan E.
    Bolton, Judith A. Hoffman
    Hunter, David J.
    Hutchinson, Amy
    Jacobs, Kevin B.
    Jenab, Mazda
    Khaw, Kay-Tee
    Kraft, Peter
    Krogh, Vittorio
    Kurtz, Robert C.
    McWilliams, Robert R.
    Mendelsohn, Julie B.
    Patel, Alpa V.
    Rabe, Kari G.
    Riboli, Elio
    Shu, Xiao-Ou
    Tjonneland, Anne
    Tobias, Geoffrey S.
    Trichopoulos, Dimitrios
    Virtamo, Jarmo
    Visvanathan, Kala
    Watters, Joanne
    Yu, Herbert
    Zeleniuch-Jacquotte, Anne
    Amundadottir, Laufey
    Stolzenberg-Solomon, Rachael Z.
    Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer2012In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 33, no 7, p. 1384-1390Article in journal (Refereed)
    Abstract [en]

    Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case-control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 x 10(-6), 1.6 x 10(-5), 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 x 10(-5)), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H.pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer.

  • 273. Li, Weiqiang
    et al.
    Middha, Mridu
    Bicak, Mesude
    Sjoberg, Daniel D.
    Vertosick, Emily
    Dahlin, Anders
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rönn, Ann-Charlotte
    Stattin, Par
    Melander, Olle
    Ulmert, David
    Lilja, Hans
    Klein, Robert J.
    Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, no 6, p. 710-719Article in journal (Refereed)
    Abstract [en]

    Background: Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging.

    Objective: To identify single nucleotide polymorphisms (SNPs) associated with death from prostate cancer.

    Design, setting, and participants: Blood samples from 11 506 men in Sweden were collected during 1991–1996. Of these, 1053 men were diagnosed with prostate cancer and 245 died from the disease. Stage and grade at diagnosis and outcome information were obtained, and DNA from all cases was genotyped.

    Outcome measurements and statistical analysis: A total of 6 126 633 SNPs were tested for association with prostate-cancer-specific survival time using a Cox proportional hazard model, adjusted for age, stage, and grade at diagnosis. A value of 1 × 10−6 was used as suggestive significance threshold. Positive candidate SNPs were tested for association with gene expression using expression quantitative trait locus analysis.

    Results and limitations: We found 12 SNPs at seven independent loci associated with prostate-cancer-specific survival time. One of 6 126 633 SNPs tested reached genome-wide significance (p < 5 × 10−8) and replicated in an independent cohort: rs73055188 (p = 5.27 × 10−9, per-allele hazard ratio [HR] = 2.27, 95% confidence interval [CI] 1.72–2.98) in the AOX1 gene. A second SNP reached a suggestive level of significance (p < 1 × 10−6) and replicated in an independent cohort: rs2702185 (p = 7.1 × 10−7, per-allele HR = 2.55, 95% CI = 1.76–3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1 expression levels, which is associated with biochemical recurrence of prostate cancer in independent cohorts. This association is yet to be validated in other ethnic groups.

    Conclusions: The SNP rs73055188 at the AOX1 locus is associated with prostate-cancer-specific survival time, and AOX1 gene expression level is correlated with biochemical recurrence of prostate cancer.

    Patient summary: We identify two genetic markers that are associated with prostate-cancer-specific survival time.

  • 274.
    Lindahl, Bernt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nilssön, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Borch-Johnsen, Knut
    Steno Diabetes Centre, Gentofte, Denmark.
    Røder, Michael E
    Department of Cardiology and Endocrinology, Nordsjaellands Hospital Hillerød, Hillerød, Denmark.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Widman, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A randomized lifestyle intervention with 5-year follow-up in subjects with impaired glucose tolerance: pronounced short-term impact but long-term adherence problems2009In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 37, no 4, p. 434-442Article in journal (Refereed)
    Abstract [en]

    AIMS: To compare data on cardiovascular risk factor changes in lipids, insulin, proinsulin, fibrinolysis, leptin and C-reactive protein, and on diabetes incidence, in relation to changes in lifestyle.

    METHODS: The study was a randomized lifestyle intervention trial conducted in northern Sweden between 1995 and 2000, in 168 individuals with impaired glucose tolerance (IGT) and body mass index above 27 at start. The intensive intervention group (n = 83) was subjected to a 1-month residential lifestyle programme. The usual care group (n = 85) participated in a health examination ending with a single counselling session. Follow-up was conducted at 1, 3 and 5 years.

    RESULTS: At 1-year follow-up, an extensive cardio-metabolic risk factor reduction was demonstrated in the intensive intervention group, along with a 70% decrease of progress to type 2 diabetes. At 5-year follow-up, most of these beneficial effects had disappeared. Reported physical activity and fibre intake as well as high-density lipoprotein cholesterol were still increased, and fasting insulin and proinsulin were lower.

    CONCLUSIONS: The intervention affected several important cardio-metabolic risk variables beneficially, and reduced the risk for type 2 diabetes, but the effects persisted only as long as the new lifestyle was maintained. Increased physical activity seemed to be the behaviour that was most easy to preserve.

  • 275. Lindkvist, Björn
    et al.
    Almquist, Martin
    Bjørge, Tone
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Institute of Preventive Medicine, Copenhagen University Hospitals, Copenhagen, Denmark.
    Borena, Wegene
    Johansen, Dorthe
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Engeland, Anders
    Nagel, Gabriele
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Selmer, Randi
    Diem, Guenter
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tretli, Steinar
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Manjer, Jonas
    Prospective cohort study of metabolic risk factors and gastric adenocarcinoma risk in the Metabolic Syndrome and Cancer Project (Me-Can)2013In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 24, no 1, p. 107-116Article in journal (Refereed)
    Abstract [en]

    Purpose: Little is known about the association between the metabolic syndrome (MetS) and the risk of gastric adenocarcinoma. The aim of this study was to investigate whether metabolic risk factors, together or combined, were associated with the risk of gastric adenocarcinoma. Methods: The Metabolic Syndrome and Cancer Project (Me-Can) is a pooling of prospective cohorts in Austria, Norway, and Sweden with information on blood pressure, lipids, glucose, and BMI available in 578,700 individuals. Cox proportional hazards analysis was used to calculate hazard ratio (HR) of gastric adenocarcinoma using metabolic risk factors categorized into quintiles and transformed into z-scores (with mean = 0 and SD = 1). The standardized sum of all z-scores created a composite MetS score. Results: In total, 1,210 incident cases of gastric adenocarcinoma were identified. Glucose was significantly associated with the risk of gastric adenocarcinoma [calibrated HR 1.58 (1.14-2.20) per one unit increment in z-score] in women. There was a statistically significant association between triglycerides and risk of gastric adenocarcinoma per mmol increment in triglycerides [HR 1.20 (1.06-1.36) per mmol] but not for the adjusted z-score in women. There were no significant association between any metabolic factors and gastric cancer among men. The composite MetS score was associated with the risk of gastric adenocarcinoma in women [HR 1.18 (1.00-1.38) per one unit increment in z-score] but not in men. Conclusions: Glucose and high levels of the composite MetS score were associated with an increased risk of gastric adenocarcinoma in women but not in men.

  • 276. Lindkvist, Björn
    et al.
    Johansen, Dorthe
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Concin, Hans
    Bjorge, Tone
    Almquist, Martin
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Engeland, Anders
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Nagel, Gabriele
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Selmer, Randi
    Ulmer, Hanno
    Tretli, Steinar
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Manjer, Jonas
    Metabolic risk factors for esophageal squamous cell carcinoma and adenocarcinoma: a prospective study of 580 000 subjects within the Me-Can project2014In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, p. 103-Article in journal (Refereed)
    Abstract [en]

    Background: Obesity is associated with an increased risk of esophageal adenocarcinoma (EAC) and a decreased risk of esophageal squamous cell carcinoma (ESCC). However, little is known about the risk of EAC and ESCC related to other metabolic risk factors. We aimed to examine the risk of EAC and ESCC in relation to metabolic risk factors, separately and combined in a prospective cohort study. Methods: The Metabolic Syndrome and Cancer cohort includes prospective cohorts in Austria, Norway and Sweden, with blood pressure, lipids, glucose and BMI available from 578 700 individuals. Relative risk (RR) for EAC and ESCC was calculated using Cox's proportional hazards analysis for metabolic risk factors categorized into quintiles and transformed into z-scores. The standardized sum of all z-scores was used as a composite score for the metabolic syndrome (MetS). Results: In total, 324 histologically verified cases of esophageal cancer were identified (114 EAC, 184 ESCC and 26 with other histology). BMI was associated with an increased risk of EAC (RR 7.34 (95% confidence interval, 2.88-18.7) top versus bottom quintile) and negatively associated with the risk of ESCC (RR 0.38 (0.23-0.62)). The mean value of systolic and diastolic blood pressure (mid blood pressure) was associated with the risk of ESCC (RR 1.77 (1.37-2.29)). The composite MetS score was associated with the risk of EAC (RR 1.56 (1.19-2.05) per one unit increase of z-score) but not ESCC. Conclusions: In accordance with previous studies, high BMI was associated with an increased risk of EAC and a decreased risk of ESCC. An association between high blood pressure and risk of ESCC was observed but alcohol consumption is a potential confounding factor that we were not able to adjust for in the analysis. The MetS was associated with EAC but not ESCC. However this association was largely driven by the strong association between BMI and EAC. We hypothesize that this association is more likely to be explained by factors directly related to obesity than the metabolic state of the MetS, considering that no other metabolic factor than BMI was associated with EAC.

  • 277. Linseisen, Jakob
    et al.
    Rohrmann, Sabine
    Bueno-de-Mesquita, Bas
    Büchner, Frederike L
    Boshuizen, Hendriek C
    Agudo, Antonio
    Gram, Inger Torhild
    Dahm, Christina C
    Overvad, Kim
    Egeberg, Rikke
    Tjønneland, Anne
    Boeing, Heiner
    Steffen, Annika
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Berrino, Franco
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Ardanaz, Eva
    Dorronsoro, Miren
    Huerta, José-Maria
    Rodríguez, Laudina
    Sánchez, María-José
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Manjer, Jonas
    Wirfält, Elisabet
    Engeset, Dagrun
    Skeie, Guri
    Katsoulis, Michael
    Oikonomou, Eleni
    Trichopoulou, Antonia
    Peeters, Petra H M
    Khaw, Kay-Tee
    Wareham, Nicholas
    Allen, Naomi
    Key, Tim
    Brennan, Paul
    Romieu, Isabelle
    Slimani, Nadia
    Vergnaud, Anne-Claire
    Xun, Wei W
    Vineis, Paolo
    Riboli, Elio
    Consumption of meat and fish and risk of lung cancer: results from the European Prospective Investigation into Cancer and Nutrition.2011In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 22, no 6, p. 909-918Article in journal (Refereed)
    Abstract [en]

    Evidence from case-control studies, but less so from cohort studies, suggests a positive association between meat intake and risk of lung cancer. Therefore, this association was evaluated in the frame of the European Prospective Investigation into Cancer and Nutrition, EPIC. Data from 478,021 participants, recruited from 10 European countries, who completed a dietary questionnaire in 1992-2000 were evaluated; 1,822 incident primary lung cancer cases were included in the present evaluation. Relative risk estimates were calculated for categories of meat intake using multi-variably adjusted Cox proportional hazard models. In addition, the continuous intake variables were calibrated by means of 24-h diet recall data to account for part of the measurement error. There were no consistent associations between meat consumption and the risk of lung cancer. Neither red meat (RR = 1.06, 95% CI 0.89-1.27 per 50 g intake/day; calibrated model) nor processed meat (RR = 1.13, 95% CI 0.95-1.34 per 50 g/day; calibrated model) was significantly related to an increased risk of lung cancer. Also, consumption of white meat and fish was not associated with the risk of lung cancer. These findings do not support the hypothesis that a high intake of red and processed meat is a risk factor for lung cancer.

  • 278. Linseisen, Jakob
    et al.
    Rohrmann, Sabine
    Miller, Anthony B
    Bueno-de-Mesquita, H Bas
    Büchner, Frederike L
    Vineis, Paolo
    Agudo, Antonio
    Gram, Inger T
    Janson, Lars
    Krogh, Vittorio
    Overvad, Kim
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Schulz, Mandy
    Pischon, Tobias
    Kaaks, Rudolf
    Nieters, Alexandra
    Allen, Naomi E
    Key, Timothy J
    Bingham, Sheila
    Khaw, Kay-Tee
    Amiano, Pilar
    Barricarte, Aurelio
    Martinez, Carmen
    Navarro, Carmen
    Quiros, Ramon
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Touvier, Mathilde
    Peeters, Petra H M
    Berglund, Göran
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lund, Eiliv
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Tjönneland, Anne
    Olsen, Anja
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Autier, Philippe
    Boffetta, Paolo
    Slimani, Nadia
    Riboli, Elio
    Fruit and vegetable consumption and lung cancer risk: Updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC).2007In: Int J Cancer, ISSN 0020-7136, Vol. 121, no 5, p. 1103-1114Article in journal (Refereed)
  • 279. Liu, Mengling
    et al.
    Lu, Wenbin
    Krogh, Vittorio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Clendenen, Tess V.
    Zeleniuch-Jacquotte, Anne
    Estimation and selection of complex covariate effects in pooled nested case-control studies with heterogeneity2013In: Biostatistics, ISSN 1465-4644, E-ISSN 1468-4357, Vol. 14, no 4, p. 682-694Article in journal (Refereed)
    Abstract [en]

    A major challenge in cancer epidemiologic studies, especially those of rare cancers, is observing enough cases. To address this, researchers often join forces by bringing multiple studies together to achieve large sample sizes, allowing for increased power in hypothesis testing, and improved efficiency in effect estimation. Combining studies, however, renders the analysis difficult owing to the presence of heterogeneity in the pooled data. In this article, motivated by a collaborative nested case-control (NCC) study of ovarian cancer in three cohorts from United States, Sweden, and Italy, we investigate the use of penalty regularized partial likelihood estimation in the context of pooled NCC studies to achieve two goals. First, we propose an adaptive group lasso (gLASSO) penalized approach to simultaneously identify important variables and estimate their effects. Second, we propose a composite agLASSO penalized approach to identify variables with heterogeneous effects. Both methods are readily implemented with the group coordinate gradient decent algorithm and shown to enjoy the oracle property. We conduct simulation studies to evaluate the performance of our proposed approaches in finite samples under various heterogeneity settings, and apply them to the pooled ovarian cancer study.

  • 280. Locke, Adam E.
    et al.
    Kahali, Bratati
    Berndt, Sonja I.
    Justice, Anne E.
    Pers, Tune H.
    Day, Felix R.
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L.
    Yang, Jian
    Croteau-Chonka, Damien C.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gustafsson, Stefan
    Kutalik, Zoltan
    Luan, Jian'an
    Maegi, Reedik
    Randall, Joshua C.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Faul, Jessica D.
    Smith, Jennifer A.
    Zhao, Jing Hua
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    Hedman, Asa K.
    Karjalainen, Juha
    Schmidt, Ellen M.
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L.
    Bragg-Gresham, L.
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B.
    Feenstra, Bjarke
    Feitosa, Mary F.
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U.
    Kanoni, Stavroula
    Kleber, Marcus E.
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Leach, Irene Mateo
    Medina-Gomez, Carolina
    Medland, Sarah E.
    Nalls, Michael A.
    Palmer, Cameron D.
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J.
    Prokopenko, Inga
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology.
    Stancakova, Alena
    Strawbridge, Rona J.
    Sung, Yun Ju
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W.
    van Settee, Jessica
    Van Vliet-Ostaptchouk, Jana V.
    Wang, Zhaoming
    Yengo, Loic
    Zhang, Weihua
    Isaacs, Aaron
    Albrecht, Eva
    Arnlov, Johan
    Arscott, Gillian M.
    Attwood, Antony P.
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N.
    Bellis, Claire
    Bennett, Amanda J.
    Berne, Christian
    Blagieva, Roza
    Blueher, Matthias
    Bohringer, Stefan
    Bonnycastle, Lori L.
    Boettcher, Yvonne
    Boyd, Heather A.
    Bruinenberg, Marcel
    Caspersen, Ida H.
    Chen, Yii-Der Ida
    Clarke, Robert
    Daw, E. Warwick
    de Craen, Anton J. M.
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S. F.
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M.
    Garcia, Melissa E.
    Geller, Frank
    Giedraitis, Vilmantas
    Gigante, Bruna
    Go, Alan S.
    Golay, Alain
    Goodall, Alison H.
    Gordon, Scott D.
    Gorski, Mathias
    Grabe, Hans-Joergen
    Grallert, Harald
    Grammer, Tanja B.
    Graessler, Jurgen
    Gronberg, Henrik
    Groves, Christopher J.
    Gusto, Gaeelle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hartman, Catharina A.
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Helmer, Qinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L.
    Jeff, Janina M.
    Johansson, Asa
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R.
    Lichtner, Peter
    Lind, Lars
    Lindstrom, Jaana
    Lo, Ken Sin
    Lobbens, Stephane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, Francois
    Magnusson, Patrik K. E.
    Mahajan, Anubha
    McArdle, Wendy L.
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L.
    Morken, Mario A.
    Mulas, Antonella
    Mueller, Gabriele
    Mueller-Nurasyid, Martina
    Musk, Arthur W.
    Nagaraja, Ramaiah
    Noethen, Markus M.
    Nolte, Ilja M.
    Pilz, Stefan
    Rayner, Nigel W.
    Renstrom, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Rettig, Rainer
    Ried, Janina S.
    Ripke, Stephan
    Robertson, Neil R.
    Rose, Lynda M.
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R.
    Scott, William R.
    Seufferlein, Thomas
    Shi, Jianxin
    Smith, Albert Vernon
    Smolonska, Joanna
    Stanton, Alice V.
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Stringham, Heather M.
    Sundstrom, Johan
    Swertz, Morris A.
    Swift, Amy J.
    Syvanen, Ann-Christine
    Tan, Sian-Tsung
    Tayo, Bamidele O.
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P.
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C.
    Vermeulen, Sita H.
    Verweij, Niek
    Vonk, Judith M.
    Waite, Lindsay L.
    Warren, Helen R.
    Waterworth, Dawn
    Weedon, Michael N.
    Wilkens, Lynne R.
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K.
    Wong, Andrew
    Wrightl, Alan F.
    Zhang, Qunyuan
    Brennan, Eoin P.
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W.
    Eriksson, Per
    Franco-Cereceda, Anders
    Gadin, Jesper R.
    Gharavi, Ali G.
    Goddard, Michael E.
    Handsaker, Robert E.
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P.
    Ma, Baoshan
    McCarroll, Steven A.
    McKnight, Amy J.
    Min, Josine L.
    Moffatt, Miriam F.
    Montgomery, Grant W.
    Murabito, Joanne M.
    Nicholson, George
    Nyholt, Dale R.
    Okada, Yukinori
    Perry, John R. B.
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M.
    Sandholm, Niina
    Scott, Robert A.
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    van 't Hooft, Ferdinand M.
    Vinkhuyzen, Anna A. E.
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T.
    Heath, Andrew C.
    Arveiler, Dominique
    Bakker, Stephan J. L.
    Beilby, John
    Bergman, Richard N.
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J.
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Crawford, Dana C.
    Cupples, L. Adrienne
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M.
    Dominiczak, Anna F.
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G.
    Farrall, Martin
    Felix, Stephan B.
    Ferrannini, Ele
    Ferrieres, Jean
    Ford, Ian
    Forouhi, Nita G.
    Forrester, Terrence
    Franco, Oscar H.
    Gansevoort, Ron T.
    Gejman, Pablo V.
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hall, Alistair S.
    Harris, Tamara B.
    Hattersley, Andrew T.
    Hicks, Andrew A.
    Hindorff, Lucia A.
    Hingorani, Aroon D.
    Hofman, Albert
    Homuth, Georg
    Hovingh, G. Kees
    Humphries, Steve E.
    Hunt, Steven C.
    Hypponen, Elina
    Illig, Thomas
    Jacobs, Kevin B.
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Jukema, J. Wouter
    Jula, Antti M.
    Kaprio, Jaakko
    Kastelein, John J. P.
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Knekt, Paul
    Kooner, Jaspal S.
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T.
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A.
    Langenberg, Claudia
    Le Marchand, Laic
    Lehtimaki, Terho
    Lyssenko, Valeriya
    Mannisto, Satu
    Marette, Andre
    Matise, Tara C.
    McKenzie, Colin A.
    McKnight, Barbara
    Moll, Frans L.
    Morris, Andrew D.
    Morris, Andrew P.
    Murray, Jeffrey C.
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ong, Ken K.
    Madden, Pamela A. F.
    Pasterkamp, Gerard
    Peden, John F.
    Peters, Annette
    Postma, Dirkje S.
    Pramstaller, Peter P.
    Price, Jackie F.
    Qi, Lu
    Raitakari, Olli T.
    Rankinen, Tuomo
    Rao, D. C.
    Rice, Treva K.
    Ridker, Paul M.
    Rioux, John D.
    Ritchie, Marylyn D.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Saramines, Jouko
    Sarzynski, Mark A.
    Schunkert, Heribert
    Schwarz, Peter E. H.
    Sever, Peter
    Shuldiner, Alan R.
    Sinisalo, Juha
    Stolk, Ronald P.
    Strauch, Konstantin
    Toenjes, Anke
    Tregouet, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Voelker, Uwe
    Waeber, Gerard
    Willemsen, Gonneke
    Witteman, Jacqueline C.
    Zillikens, M. Carola
    Adair, Linda S.
    Amouyel, Philippe
    Asselbergs, Folkert W.
    Assimes, Themistocles L.
    Bochud, Murielle
    Boehm, Bernhard O.
    Boerwinkle, Eric
    Bornstein, Stefan R.
    Bottinger, Erwin P.
    Bouchard, Claude
    Cauchi, Stephane
    Chambers, John C.
    Chanock, Stephen J.
    Cooper, Richard S.
    de Bakker, Paul I. W.
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Froguel, Philippe
    Groop, Leif C.
    Haiman, Christopher A.
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J.
    Hveem, Kristian
    Kaplan, Robert C.
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G.
    Maerz, Winfried
    Melbve, Mads
    Metspalu, Andres
    Moebus, Susanne
    Munroe, Patricia B.
    Njolstad, Inger
    Oostra, Ben A.
    Palmer, Colin N. A.
    Pedersen, Nancy L.
    Perola, Markus
    Perusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E.
    Saleheen, Danish
    Sattar, Naveed
    Schadt, Eric E.
    Schlessinger, David
    Slagboom, P. Eline
    Snieder, Harold
    Spector, Tim D.
    Thorsteinsdottir, Unnu R.
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wichmann, H-Erich
    Wilson, James F.
    Zanen, Pieter
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Heid, Iris M.
    O'Connell, Jeffrey R.
    Strachan, David P.
    Stefansson, Kari
    van Duijri, Cornelia M.
    Abecasis, Goncalo R.
    Franke, Lude
    Frayling, Timothy M.
    McCarthy, Mark I.
    Visscher, Peter M.
    Scherag, Andre
    Willer, Cristen J.
    Boehnke, Michael
    Mohlke, Karen L.
    Lindgren, Cecilia M.
    Beckmann, Jacques S.
    Barroso, Ines
    North, Kari E.
    Ingelsson, Erik
    Hirschhorn, Joel N.
    Loos, Ruth J. F.
    Speliotes, Elizabeth K.
    Genetic studies of body mass index yield new insights for obesity biology2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, p. 197-U401Article in journal (Refereed)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 281. Lu, Yunxia
    et al.
    Zamora-Ros, Raul
    Chan, Simon
    Cross, Amanda J.
    Ward, Heather
    Jakszyn, Paula
    Luben, Robert
    Opstelten, Jorrit L.
    Oldenburg, Bas
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Grip, Olof
    Key, Timothy
    Bergmann, Manuela M.
    Boeing, Heiner
    Overvad, Kim
    Palli, Domenico
    Masala, Giovanna
    Khaw, Kay-Tee
    Racine, Antoine
    Carbonnel, Franck
    Boutron-Ruault, Marie-Christine
    Andersen, Vibeke
    Olsen, Anja
    Tjonneland, Anne
    Kaaks, Rudolf
    Tumino, Rosario
    Trichopoulou, Antonia
    Scalbert, Augustin
    Riboli, Elio
    Hart, Andrew R.
    Dietary Polyphenols in the Aetiology of Crohn's Disease and Ulcerative Colitis-A Multicenter European Prospective Cohort Study (EPIC)2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 12, p. 2072-2082Article in journal (Refereed)
    Abstract [en]

    Background: Oxidative stress may be involved in the aetiology of inflammatory bowel disease and whether dietary polyphenols, which possess antioxidants properties, prevent its development is unknown.

    Methods: A total of 401,326 men and women aged 20 to 80 years from 8 countries were recruited between 1991 and 1998 and at baseline completed validated food frequency questionnaires. Dietary polyphenol intake was measured using Phenol-Explorer, a database with information on the content of 502 polyphenols. Incident cases of Crohn's diseases (CD) and ulcerative colitis (UC) were identified during the follow-up period of up to December 2010. A nested case–control study using conditional logistic regression estimated the odds ratios (ORs), and 95% confidence intervals, for polyphenol intake (categories based on quartiles) and developing CD or UC.

    Results: In total, 110 CD (73% women) and 244 UC (57% women) cases were identified and matched to 440 and 976 controls, respectively. Total polyphenol intake was not associated with CD ( P trend = 0.17) or UC ( P trend = 0.16). For flavones and CD, there were reduced odds for all quartiles, which were statistically significant for the third (OR 3rd versus 1st quartile = 0.33; 95% confidence interval, 0.15–0.69) and there was an inverse trend across quartiles ( P = 0.03). Similarly, for resveratrol, there was an inverse association with CD (OR 4th versus 1st quartile = 0.40; 95% confidence interval, 0.20–0.82) with an inverse trend across quartiles ( P = 0.02). No significant associations between subtypes of polyphenols and UC were found. Effect modification by smoking in CD was documented with borderline statistical significance.

    Conclusions: The data supports a potential role of flavones and resveratrol in the risk of developing CD; future aetiological studies should investigate these dietary components and further examine the potential for residual confounding.

  • 282.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kaaks, Rudolf
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Body mass index and cancer: results from the Northern Sweden Health and Disease Cohort2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 118, no 2, p. 458-466Article in journal (Refereed)
    Abstract [en]

    Excess weight has been associated with increased risk of cancer. The effect of body mass index (BMI, kg/m(2)) on overall cancer risk and on risk of developing several common cancer types was examined in a population-based cohort study. Height and weight measurements were available for 35,362 women and 33,424 men recruited in the Northern Sweden Health and Disease Cohort between 1985 and 2003. Among cohort members, 2,691 incident cancer cases were identified. The association of BMI with cancer risk was examined using Poisson regression. Women with BMI > 27.1 (top quartile) had a 29% higher risk of developing any malignancy compared to women with BMI of 18.5-22.2 (lowest quartile), which increased to 47% in analysis limited to nonsmokers. Analyses according to WHO cut-off points showed that obese women (BMI > or = 30) had a 36% higher risk of cancer than women with BMI in the normal range (18.5-25). Individual cancer sites most strongly related to obesity were endometrium (risk for top quartile = 3.53, 95% confidence interval 1.86-7.43), ovary (2.09, 1.13-4.13) and colon (2.05, 1.04-4.41). BMI was inversely related to breast cancer occurring before age 49 (0.58, 0.29-1.11, p(trend) < 0.04). In men, there was no association of BMI with overall cancer risk. Obese men (BMI > or = 30), however, were at increased risk of developing kidney cancer (3.63, 1.23-10.7) and, after exclusion of cases diagnosed within 1 year of recruitment, colon cancer (1.77, 1.04-2.95). Our study provides further evidence that BMI is positively associated with cancer risk. In women from northern Sweden, up to 7% of all cancers were attributable to overweight and obesity and could be avoided by keeping BMI within the recommended range.

  • 283.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Akhmedkhanov, Arslan
    Micheli, Andrea
    Rinaldi, Sabina
    Zeleniuch-Jacquotte, Anne
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Muti, Paola
    Biessy, Carine
    Krogh, Vittorio
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Riboli, Elio
    Kaaks, Rudolf
    Toniolo, Paolo
    Circulating levels of sex steroid hormones and risk of ovarian cancer.2003In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 104, no 5, p. 636-642Article in journal (Refereed)
    Abstract [en]

    Experimental and epidemiological evidence supports a role for sex steroid hormones in the pathogenesis of ovarian cancer. We investigated the association between ovarian cancer risk and pre-diagnostic blood concentrations of testosterone, androstenedione, DHEAS, estrone and SHBG. A case-control study nested within 3 cohorts, in New York (USA), Umeå (Sweden) and Milan (Italy), included 132 subjects with primary invasive epithelial ovarian cancer. For each case subject, 2 controls were selected who matched a case on cohort, menopausal status, age and date of recruitment and, if premenopausal, day of the menstrual cycle at blood donation. Only women who did not use exogenous hormones at blood donation were included in the study. Conditional logistic regression was used to relate cancer risk to sex steroid hormone concentrations with adjustment for potential confounders. No clear association was observed between ovarian cancer risk and any of the 5 hormones under study. In the premenopausal group, the risk appeared to increase with increasing blood concentrations of androstenedione (upper vs. lower tertile OR = 2.35; 95% CI = 0.81-6.82.), but the small number of subjects in the sub-group precluded reaching unambiguous conclusions about such association. Our study does not support previous observations relating elevations in blood levels of the major sex steroid hormones to an increased risk of ovarian cancer, but offers some evidence that elevated circulating androstenedione before menopause may be associated with increased ovarian cancer risk.

  • 284.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Micheli, Andrea
    Akhmedkhanov, Arslan
    Rinaldi, Sabina
    Muti, Paola
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Biessy, Carine
    Krogh, Vittorio
    Riboli, Elio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Berrino, Franco
    Zeleniuch-Jacquotte, Anne
    Toniolo, Paolo
    Kaaks, Rudolf
    Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy).2003In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 14, no 3, p. 285-292Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the association of prediagnostic circulating levels of C-peptide, as a marker of pancreatic insulin secretion, and IGF binding proteins -1 and -2, as indicators of the biologically active IGF-I concentration, with risk of developing ovarian cancer. METHODS: The study was nested within three prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Case subjects were 132 women with primary invasive epithelial ovarian cancer diagnosed at least one year after blood donation. For each case, two control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. RESULTS: Odds ratios and their 95% confidence intervals for risk of developing ovarian cancer over quartiles of peptides concentrations after adjustment for BMI and fasting were: 1.00, 0.66 (0.35-1.23), 0.96 (0.51-1.82) and 0.89 (0.44-1.81) for C-peptide; 1.00, 1.10 (0.58-2.09), 1.07 (0.55-2.04) and 0.79 (0.38-1.62) for IGFBP-1; and 1.00, 1.01 (0.54-1.89), 0.98 (0.51-1.88) and 0.87 (0.45-1.68) for IGFBP-2. In women who had ovarian cancer diagnosis before age 55 the ORs for the top tertiles of IGFBP-1 and IGFBP-2 were 0.51 (0.18-1.49) and 0.53 (0.18-1.54), respectively. CONCLUSIONS: This study does not support an independent direct etiological role of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before age 55.

  • 285.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Micheli, Andrea
    Arslan, Alan
    Ferrari, Pietro
    Rinaldi, Sabina
    Krogh, Vittorio
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shore, Roy E
    Biessy, Carine
    Muti, Paola
    Riboli, Elio
    Koenig, Karen L
    Levitz, Mortimer
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Kaaks, Rudolf
    Toniolo, Paolo
    Zeleniuch-Jacquotte, Anne
    Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 108, no 3, p. 425-432Article in journal (Refereed)
    Abstract [en]

    Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.

  • 286.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Toniolo, Paolo
    Micheli, Andrea
    Akhmedkhanov, Arslan
    Rinaldi, Sabina
    Muti, Paola
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Biessy, Carine
    Krogh, Vittorio
    Zeleniuch-Jacquotte, Anne
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Riboli, Elio
    Kaaks, Rudolf
    Circulating levels of insulin-like growth factor-I and risk of ovarian cancer.2002In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 101, no 6, p. 549-554Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor (IGF)-I, a mitogenic and anti-apoptotic peptide, has been implicated in the development of several cancers. We hypothesized that high circulating IGF-I concentrations may be associated with an increased risk of ovarian cancer. A case-control study was nested within 3 prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). One hundred thirty-two women with primary invasive epithelial ovarian cancer diagnosed at least 1 year after blood donation were case subjects. For each case, 2 control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. There was no association between IGF-I concentrations and ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at a young age (<55), circulating IGF-I was directly and strongly associated with ovarian cancer risk (OR = 4.97; 95% CI = 1.22-20.2 for the top vs. the bottom IGF-I tertile after adjustment for parity, BMI categories and smoking). There was no significant association of IGF binding protein-3 with ovarian cancer risk. We found a strong direct relationship between circulating IGF-I levels and risk of developing ovarian cancer before age 55. Additional, larger studies of this association are needed to provide more precise estimates of effect.

  • 287.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zeleniuch-Jacquotte, A
    Muti, P
    Mure, A
    Rinaldi, S
    Dossus, L
    Micheli, A
    Arslan, A
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shore, R E
    Krogh, V
    Koenig, K L
    Riboli, E
    Berrino, F
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Toniolo, P
    Kaaks, R
    Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.2004In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 150, no 2, p. 161-171Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

  • 288.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Zeleniuch-Jacquotte, Anne
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Arslan, Alan A
    Afanasyeva, Yelena
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. null.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. null.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. null.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. null.
    Insulin-like growth factor I in pregnancy and maternal risk of breast cancer2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 12, p. 2489-2493Article in journal (Refereed)
    Abstract [en]

    Background: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy.

    Methods: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).

    Results: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II.

    Conclusions: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy.

  • 289.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zeleniuch-Jacquotte, Anne
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Micheli, Andrea
    Arslan, Alan A
    Rinaldi, Sabina
    Muti, Paola
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Koenig, Karen L
    Biessy, Carine
    Krogh, Vittorio
    Riboli, Elio
    Shore, Roy E
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Kaaks, Rudolf
    Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 108, no 2, p. 262-268Article in journal (Refereed)
    Abstract [en]

    Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.

  • 290. Lumbreras, B
    et al.
    Garte, S
    Overvad, K
    Tjonneland, A
    Clavel-Chapelon, F
    Linseisen, J P
    Boeing, H
    Trichopoulou, A
    Palli, D
    Peluso, M
    Krogh, V
    Tumino, R
    Panico, S
    Bueno-De-Mesquita, H B
    Peeters, P H
    Lund, E
    Martinez, C
    Dorronsoro, M
    Barricarte, A
    Chirlaque, M-D
    Quiros, J R
    Berglund, G
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Day, N E
    Key, T J
    Saracci, R
    Kaaks, R
    Malaveille, C
    Ferrari, P
    Boffetta, P
    Norat, T
    Riboli, E
    Gonzalez, C A
    Vineis, P
    Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?2008In: Cancer Causes Control, ISSN 0957-5243, Vol. 19, no 6, p. 649-56Article in journal (Refereed)
  • 291. Lumme, Sonja
    et al.
    Tenkanen, Leena
    Langseth, Hilde
    Gislefoss, Randi
    Hakama, Matti
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Adlercreutz, Herman
    Saikku, Pekka
    Stenman, Ulf-Hakan
    Tuohimaa, Pentti
    Luostarinen, Tapio
    Dillner, Joakim
    Longitudinal biobanks-based study on the joint effects of infections, nutrition and hormones on risk of prostate cancer2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 7, p. 839-845Article in journal (Refereed)
    Abstract [en]

    Background To evaluate the individual and combined effects of enterolactone, vitamin D, free testosterone, Chlamydia trachomatis and HPV-18 on the risk of prostate cancer in a large population-based biochemical material that combined three Nordic serum sample banks. Material and methods A joint cohort of 209000 healthy men was followed using cancer registry linkages. From this cohort altogether 699 incident cases of prostate cancer were identified. Four controls were selected by incidence density sampling and matching for country, age and date of the blood sampling. Complete data for all investigated exposures was available for 483 eligible cases and 1055 eligible controls. Multivariate regression analyses were performed to investigate the solitary and combined effects. Results The solitary effects were small. Significantly increased risk [rate ratio 1.6 (95% CI 1.0-2.5)] was found in those seronegative for C. trachomatis infection. The joint effect in risk levels of enterolactone and vitamin D was antagonistic [observed rate ratio (RR) 1.4 (1.0-2.1), expected RR 2.0 (1.0-4.1)] as well as that of HPV-18 and C. trachomatis [observed RR 1.9 (0.8-4.5), expected RR 9.9 (1.1-87.0)]. Conclusion A large follow-up study combining data from several previously investigated exposures to investigate joint effects found no evidence that exposure to two risk factors would increase the risk of prostate cancer from that expected on basis of exposure to one risk factor. If anything, the results were consistent with antagonistic interactions.

  • 292.
    Lundin, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dossus, Laure
    Clendenen, Tess
    Krogh, Vittorio
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sieri, Sabina
    Arslan, Alan
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Zeleniuch-Jacquotte, Anne
    Toniolo, Paolo
    Lukanova, Annekatrin
    C-reactive protein and ovarian cancer: a prospective study nested in three cohorts (Sweden, USA, Italy).2009In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 20, no 7, p. 1151-1159Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Inflammatory processes may influence the risk of epithelial ovarian cancer, but available epidemiological evidence is limited and indirect. Circulating C-reactive protein (CRP), a sensitive marker of inflammation, may serve as a direct biological marker of an underlying association. METHODS: The association between ovarian cancer risk and pre-diagnostic circulating CRP was tested in a case-control study nested within three prospective cohorts from Sweden, USA, and Italy. The study included 237 cases and 427 individually matched controls. CRP was measured in stored blood samples by high-sensitivity immunoturbidimetric assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. RESULTS: Overall, CRP was not related to risk of ovarian cancer. However, a marked increase in risk was observed for CRP concentrations >10 mg/l: OR (95% CI) 4.4 (1.8-10.9), which remained significant after limiting analyses to cases diagnosed more than two or five years after blood donation (OR 3.0 (1.2-8.0) and 3.6 (1.0-13.2), respectively). Risk of mucinous tumors increased with high CRP, but the number of cases in this analysis was small. CONCLUSION: Study results offer additional support to the concept that chronic inflammation plays a role in epithelial ovarian cancer.

  • 293.
    Lundin, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wirgin, Isaac
    Lukanova, Annekatrin
    Afanasyeva, Yelena
    Krogh, Vittorio
    Axelsson, Tomas
    Hemminki, Kari
    Clendenen, Tess V
    Arslan, Alan A
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sieri, Sabina
    Roy, Nirmal
    Koenig, Karen L
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Berrino, Franco
    Toniolo, Paolo
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Försti, Asta
    Muti, Paola
    Lenner, Per
    Shore, Roy E
    Zeleniuch-Jacquotte, Anne
    Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer2012In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 36, no 5, p. 445-452Article in journal (Refereed)
    Abstract [en]

    Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.

  • 294.
    Lundin, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lairon, D
    Tidehag, P
    Aman, P
    Adlercreutz, H
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Effects of meal frequency and high-fibre rye-bread diet on glucose and lipid metabolism and ileal excretion of energy and sterols in ileostomy subjects.2004In: European Journal of Clinical Nutrition, ISSN 0954-3007, Vol. 58, no 10, p. 1410-9Article in journal (Refereed)
  • 295. Luostarinen, T
    et al.
    Lehtinen, M
    Björge, T
    Abeler, V
    Hakama, M
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jellum, E
    Koskela, P
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Lie, A K
    Paavonen, J
    Pukkala, E
    Saikku, P
    Sigstad, E
    Thoresen, S
    Youngman, L D
    Dillner, J
    Hakulinen, T
    Joint effects of different human papillomaviruses and Chlamydia trachomatis infections on risk of squamous cell carcinoma of the cervix uteri2004In: European Journal of Cancer, ISSN 0959-8049, Vol. 40, no 7, p. 1058-1065Article in journal (Refereed)
  • 296.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Zetterberg, Henrik
    Blennow, Kaj
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Plasma concentrations of free amyloid β cannot predict the development of Alzheimer's disease2017In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, no 7, p. 778-782Article in journal (Refereed)
    Abstract [en]

    Introduction: Biomarkers that identify individuals at risk of Alzheimer's disease (AD) development would be highly valuable. Plasma concentration of amyloid β (Aβ)—central in the pathogenesis of AD—is a logical candidate, but studies to date have produced conflicting results on its utility.

    Methods: Plasma samples from 339 preclinical AD cases (76.4% women, mean age 61.3 years) and 339 age- and sex-matched dementia-free controls, taken an average of 9.4 years before AD diagnosis, were analyzed using Luminex xMAP technology and INNO-BIA plasma Aβ form assays to determine concentrations of free plasma Aβ40 and Aβ42.

    Results: Plasma concentrations of free Aβ40 and Aβ42 did not differ between preclinical AD cases and dementia-free controls, in the full sample or in subgroups defined according to sex and age group (<60 and ≥ 60 years). The interval between sampling and AD diagnosis did not affect the results. Aβ concentrations did not change in the years preceding AD diagnosis among individuals for whom longitudinal samples were available.

    Discussion: Plasma concentrations of free Aβ could not predict the development of clinical AD, and Aβ concentrations did not change in the years preceding AD diagnosis in this sample. These results indicate that free plasma Aβ is not a useful biomarker for the identification of individuals at risk of developing clinical AD.

  • 297.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Gilthorpe, Jonathan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Herpes simplex infection and the risk of Alzheimer's disease: a nested case-control study2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 6, p. 587-592Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Herpes simplex virus (HSV) is thought to play an etiological role in the development of Alzheimer's disease (AD).

    METHODS: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years) and 360 age- and sex-matched dementia-free controls, taken on average 9.6 years before AD diagnosis, were analyzed for anti-HSV antibodies (immunoglobulin G, IgG, and immunoglobulin M, IgM) by enzyme-linked immunosorbent assays.

    RESULTS: In the complete sample group, the presence of anti-HSV IgG and IgM antibodies did not increase the risk of AD significantly (odds ratio (OR) 1.636, P = .069 and OR 1.368, P = .299, respectively). In cases with 6.6 years or more between plasma sampling and AD diagnosis (n = 270), there was a significant association between presence of anti-HSV IgG antibodies and AD (OR 2.250, P = .019).

    CONCLUSION: Among persons with a follow-up time of 6.6 years or more, HSV infection was significantly associated with AD.

  • 298.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer’s Disease Development2018In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, p. 939-945Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several environmental factors, including infectious agents, have been suggested to cause Alzheimer's disease (AD). Cytomegalovirus (CMV) has been associated with AD in several recent studies.

    OBJECTIVE: To investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD.

    METHODS: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years), taken an average of 9.6 years before AD diagnosis, and 360 age-, sex-, cohort-, and sampling date matched dementia-free controls were analyzed to detect anti-CMV (immunoglobulin [Ig] G and IgM), group-specific anti-HSV (IgG and IgM), and specific anti-HSV1 and HSV2 IgG antibodies by enzyme-linked immunosorbent assays. AD cases and dementia-free controls were compared using conditional logistic regression analyses.

    RESULTS: The presence of anti-CMV IgG antibodies did not increase the risk of AD (odds ratio [OR], 0.857; p = 0.497). Among AD cases, an association between CMV and HSV1 carriage was detected (OR 7.145, p < 0.001); in a conditional logistic regression model, the interaction between CMV and HSV1 was associated with AD development (OR 5.662; p = 0.007).

    CONCLUSION: The present findings do not support a direct relationship between CMV infection and the development of AD; however, an interaction between CMV and HSV1 was found to be associated significantly with AD development. These findings suggest that CMV infection facilitates the development of HSV1-associated AD, possibly via its effects on the immune system.

  • 299. Machiela, Mitchell J
    et al.
    Zhou, Weiyin
    Karlins, Eric
    Sampson, Joshua N
    Freedman, Neal D
    Yang, Qi
    Hicks, Belynda
    Dagnall, Casey
    Hautman, Christopher
    Jacobs, Kevin B
    Abnet, Christian C
    Aldrich, Melinda C
    Amos, Christopher
    Amundadottir, Laufey T
    Arslan, Alan A
    Beane-Freeman, Laura E
    Berndt, Sonja I
    Black, Amanda
    Blot, William J
    Bock, Cathryn H
    Bracci, Paige M
    Brinton, Louise A
    Bueno-de-Mesquita, H Bas
    Burdett, Laurie
    Buring, Julie E
    Butler, Mary A
    Canzian, Federico
    Carreón, Tania
    Chaffee, Kari G
    Chang, I-Shou
    Chatterjee, Nilanjan
    Chen, Chu
    Chen, Constance
    Chen, Kexin
    Chung, Charles C
    Cook, Linda S
    Crous Bou, Marta
    Cullen, Michael
    Davis, Faith G
    De Vivo, Immaculata
    Ding, Ti
    Doherty, Jennifer
    Duell, Eric J
    Epstein, Caroline G
    Fan, Jin-Hu
    Figueroa, Jonine D
    Fraumeni, Joseph F
    Friedenreich, Christine M
    Fuchs, Charles S
    Gallinger, Steven
    Gao, Yu-Tang
    Gapstur, Susan M
    Garcia-Closas, Montserrat
    Gaudet, Mia M
    Gaziano, J Michael
    Giles, Graham G
    Gillanders, Elizabeth M
    Giovannucci, Edward L
    Goldin, Lynn
    Goldstein, Alisa M
    Haiman, Christopher A
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hankinson, Susan E
    Harris, Curtis C
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holly, Elizabeth A
    Hong, Yun-Chul
    Hoover, Robert N
    Hsiung, Chao A
    Hu, Nan
    Hu, Wei
    Hunter, David J
    Hutchinson, Amy
    Jenab, Mazda
    Johansen, Christoffer
    Khaw, Kay-Tee
    Kim, Hee Nam
    Kim, Yeul Hong
    Kim, Young Tae
    Klein, Alison P
    Klein, Robert
    Koh, Woon-Puay
    Kolonel, Laurence N
    Kooperberg, Charles
    Kraft, Peter
    Krogh, Vittorio
    Kurtz, Robert C
    LaCroix, Andrea
    Lan, Qing
    Landi, Maria Teresa
    Marchand, Loic Le
    Li, Donghui
    Liang, Xiaolin
    Liao, Linda M
    Lin, Dongxin
    Liu, Jianjun
    Lissowska, Jolanta
    Lu, Lingeng
    Magliocco, Anthony M
    Malats, Nuria
    Matsuo, Keitaro
    McNeill, Lorna H
    McWilliams, Robert R
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Mirabello, Lisa
    Moore, Lee
    Olson, Sara H
    Orlow, Irene
    Park, Jae Yong
    Patiño-Garcia, Ana
    Peplonska, Beata
    Peters, Ulrike
    Petersen, Gloria M
    Pooler, Loreall
    Prescott, Jennifer
    Prokunina-Olsson, Ludmila
    Purdue, Mark P
    Qiao, You-Lin
    Rajaraman, Preetha
    Real, Francisco X
    Riboli, Elio
    Risch, Harvey A
    Rodriguez-Santiago, Benjamin
    Ruder, Avima M
    Savage, Sharon A
    Schumacher, Fredrick
    Schwartz, Ann G
    Schwartz, Kendra L
    Seow, Adeline
    Wendy Setiawan, Veronica
    Severi, Gianluca
    Shen, Hongbing
    Sheng, Xin
    Shin, Min-Ho
    Shu, Xiao-Ou
    Silverman, Debra T
    Spitz, Margaret R
    Stevens, Victoria L
    Stolzenberg-Solomon, Rachael
    Stram, Daniel
    Tang, Ze-Zhong
    Taylor, Philip R
    Teras, Lauren R
    Tobias, Geoffrey S
    Van Den Berg, David
    Visvanathan, Kala
    Wacholder, Sholom
    Wang, Jiu-Cun
    Wang, Zhaoming
    Wentzensen, Nicolas
    Wheeler, William
    White, Emily
    Wiencke, John K
    Wolpin, Brian M
    Wong, Maria Pik
    Wu, Chen
    Wu, Tangchun
    Wu, Xifeng
    Wu, Yi-Long
    Wunder, Jay S
    Xia, Lucy
    Yang, Hannah P
    Yang, Pan-Chyr
    Yu, Kai
    Zanetti, Krista A
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Zhou, Baosen
    Ziegler, Regina G
    Perez-Jurado, Luis A
    Caporaso, Neil E
    Rothman, Nathaniel
    Tucker, Margaret
    Dean, Michael C
    Yeager, Meredith
    Chanock, Stephen J
    Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome2016In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, article id 11843Article in journal (Refereed)
    Abstract [en]

    To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

  • 300. Machiela, Mitchell J.
    et al.
    Zhou, Weiyin
    Sampson, Joshua N.
    Dean, Michael C.
    Jacobs, Kevin B.
    Black, Amanda
    Brinton, Louise A.
    Chang, I-Shou
    Chen, Chu
    Chen, Constance
    Chen, Kexin
    Cook, Linda S.
    Bou, Marta Crous
    De Vivo, Immaculata
    Doherty, Jennifer
    Friedenreich, Christine M.
    Gaudet, Mia M.
    Haiman, Christopher A.
    Hankinson, Susan E.
    Hartge, Patricia
    Henderson, Brian E.
    Hong, Yun-Chul
    Hosgood, H. Dean, III
    Hsiung, Chao A.
    Hu, Wei
    Hunter, David J.
    Jessop, Lea
    Kim, Hee Nam
    Kim, Yeul Hong
    Kim, Young Tae
    Klein, Robert
    Kraft, Peter
    Lan, Qing
    Lin, Dongxin
    Liu, Jianjun
    Le Marchand, Loic
    Liang, Xiaolin
    Lissowska, Jolanta
    Lu, Lingeng
    Magliocco, Anthony M.
    Matsuo, Keitaro
    Olson, Sara H.
    Orlow, Irene
    Park, Jae Yong
    Pooler, Loreall
    Prescott, Jennifer
    Rastogi, Radhai
    Risch, Harvey A.
    Schumacher, Fredrick
    Seow, Adeline
    Setiawan, Veronica Wendy
    Shen, Hongbing
    Sheng, Xin
    Shin, Min-Ho
    Shu, Xiao-Ou
    VanDen Berg, David
    Wang, Jiu-Cun
    Wentzensen, Nicolas
    Wong, Maria Pik
    Wu, Chen
    Wu, Tangchun
    Wu, Yi-Long
    Xia, Lucy
    Yang, Hannah P.
    Yang, Pan-Chyr
    Zheng, Wei
    Zhou, Baosen
    Abnet, Christian C.
    Albanes, Demetrius
    Aldrich, Melinda C.
    Amos, Christopher
    Amundadottir, Laufey T.
    Berndt, Sonja I.
    Blot, William J.
    Bock, Cathryn H.
    Bracci, Paige M.
    Burdett, Laurie
    Buring, Julie E.
    Butler, Mary A.
    Carreon, Tania
    Chatterjee, Nilanjan
    Chung, Charles C.
    Cook, Michael B.
    Cullen, Michael
    Davis, Faith G.
    Ding, Ti
    Duell, Eric J.
    Epstein, Caroline G.
    Fan, Jin-Hu
    Figueroa, Jonine D.
    Fraumeni, Joseph F., Jr.
    Freedman, Neal D.
    Fuchs, Charles S.
    Gao, Yu-Tang
    Gapstur, Susan M.
    Patino-Garcia, Ana
    Garcia-Closas, Montserrat
    Gaziano, J. Michael
    Giles, Graham G.
    Gillanders, Elizabeth M.
    Giovannucci, Edward L.
    Goldin, Lynn
    Goldstein, Alisa M.
    Greene, Mark H.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Harris, Curtis C.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holly, Elizabeth A.
    Hoover, Robert N.
    Hu, Nan
    Hutchinson, Amy
    Jenab, Mazda
    Johansen, Christoffer
    Khaw, Kay-Tee
    Koh, Woon-Puay
    Kolonel, Laurence N.
    Kooperberg, Charles
    Krogh, Vittorio
    Kurtz, Robert C.
    LaCroix, Andrea
    Landgren, Annelie
    Landi, Maria Teresa
    Li, Donghui
    Liao, Linda M.
    Malats, Nuria
    McGlynn, Katherine A.
    McNeill, Lorna H.
    McWilliams, Robert R.
    Melin, Beatrice S.
    Mirabello, Lisa
    Peplonska, Beata
    Peters, Ulrike
    Petersen, Gloria M.
    Prokunina-Olsson, Ludmila
    Purdue, Mark
    Qiao, You-Lin
    Rabe, Kari G.
    Rajaraman, Preetha
    Real, Francisco X.
    Riboli, Elio
    Rodriguez-Santiago, Benjamin
    Rothman, Nathaniel
    Ruder, Avima M.
    Savage, Sharon A.
    Schwartz, Ann G.
    Schwartz, Kendra L.
    Sesso, Howard D.
    Severi, Gianluca
    Silverman, Debra T.
    Spitz, Margaret R.
    Stevens, Victoria L.
    Stolzenberg-Solomon, Rachael
    Stram, Daniel
    Tang, Ze-Zhong
    Taylor, Philip R.
    Teras, Lauren R.
    Tobias, Geoffrey S.
    Viswanathan, Kala
    Wacholder, Sholom
    Wang, Zhaoming
    Weinstein, Stephanie J.
    Wheeler, William
    White, Emily
    Wiencke, John K.
    Wolpin, Brian M.
    Wu, Xifeng
    Wunder, Jay S.
    Yu, Kai
    Zanetti, Krista A.
    Zeleniuch-Jacquotte, Anne
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Ziegler, Regina G.
    De Andrade, Mariza
    Barnes, Kathleen C.
    Beaty, Terri H.
    Bierut, Laura J.
    Desch, Karl C.
    Doheny, Kimberly F.
    Feenstra, Bjarke
    Ginsburg, David
    Heit, John A.
    Kang, Jae H.
    Laurie, Cecilia A.
    Li, Jun Z.
    Lowe, William L.
    Marazita, Mary L.
    Melbye, Mads
    Mirel, Daniel B.
    Murray, Jeffrey C.
    Nelson, Sarah C.
    Pasquale, Louis R.
    Rice, Kenneth
    Wiggs, Janey L.
    Wise, Anastasia
    Tucker, Margaret
    Perez-Jurado, Luis A.
    Laurie, Cathy C.
    Caporaso, Neil E.
    Yeager, Meredith
    Chanock, Stephen J.
    Characterization of Large Structural Genetic Mosaicism in Human Autosomes2015In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 96, no 3, p. 487-497Article in journal (Refereed)
    Abstract [en]

    Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

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