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  • 151.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Huyghe, Jeroen R.
    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.
    Meyer, Klaus
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ueland, Per Magne
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196233Article in journal (Refereed)
    Abstract [en]

    Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes. This nested case-control study included 488 CRC cases and 947 matched controls from two population-based cohorts in the Northern Sweden Health and Disease Study. We analyzed 14 biomarkers and 17 SNPs in prediagnostic blood and determined KRAS and BRAF mutation status in tumor tissue. In a multivariate network analysis, no variable displayed a strong association with the risk of specific CRC subtypes. A non-synonymous SNP in the CTH gene, rs1021737, had a stronger association compared with other variables. In subsequent univariate analyses, participants with variant rs1021737 genotype had a decreased risk of KRAS-mutated CRC (OR per allele = 0.72, 95% CI = 0.50, 1.05), and an increased risk of BRAF-mutated CRC (OR per allele = 1.56, 95% CI = 1.07, 2.30), with weak evidence for heterogeneity (Pheterogeneity = 0.01). This subtype-specific SNP association was not replicated in a case-case analysis of 533 CRC cases from The Cancer Genome Atlas (P = 0.85). In conclusion, we found no support for clear subtype-specific roles of one-carbon metabolism biomarkers and SNPs in CRC development, making differences in CRC molecular subtype distributions an unlikely explanation for the varying results on the role of one-carbon metabolism in CRC development across previous studies. Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.

  • 152.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Ueland, Per Magne
    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.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43434Article in journal (Refereed)
    Abstract [en]

    The role of one-carbon metabolism (1CM), particularly folate, in colorectal cancer (CRC) development has been extensively studied, but with inconclusive results. Given the complexity of 1CM, the conventional approach, investigating components individually, may be insufficient. We used a machine learning-based Bayesian network approach to study, simultaneously, 14 circulating one-carbon metabolites, 17 related single nucleotide polymorphisms (SNPs), and several environmental factors in relation to CRC risk in 613 cases and 1190 controls from the prospective Northern Sweden Health and Disease Study. The estimated networks corresponded largely to known biochemical relationships. Plasma concentrations of folate (direct), vitamin B6 (pyridoxal 5-phosphate) (inverse), and vitamin B2 (riboflavin) (inverse) had the strongest independent associations with CRC risk. Our study demonstrates the importance of incorporating B-vitamins in future studies of 1CM and CRC development, and the usefulness of Bayesian network learning for investigating complex biological systems in relation to disease.

  • 153.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Ueland, Per Magne
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    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.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk2016In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 27, no 6, p. 787-796Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate.

    METHODS: This was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based Northern Sweden Health and Disease Study. We estimated odds ratios (OR) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort.

    RESULTS: Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (OR [95% confidence interval {CI}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). Estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. The inverse association of methionine was modified by plasma folate concentrations (OR [95% CI] for highest/lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], Pinteraction = 0.06).

    CONCLUSIONS: In this population-based, nested case-control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk. See Video Abstract at http://links.lww.com/EDE/B83.

  • 154. Naudin, Sabine
    et al.
    Li, Kuanrong
    Jaouen, Tristan
    Assi, Nada
    Kyrø, Cecilie
    Tjønneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Rebours, Vinciane
    Védié, Anne-Laure
    Boeing, Heiner
    Kaaks, Rudolf
    Katzke, Verena
    Bamia, Christina
    Naska, Androniki
    Trichopoulou, Antonia
    Berrino, Franco
    Tagliabue, Giovanna
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Peeters, Petra H
    Bueno-de-Mesquita, Bas
    Weiderpass Vainio, Elisabete
    Gram, Inger Torhild
    Skeie, Guri
    Chirlaque, Maria-Dolores
    Rodríguez-Barranco, Miguel
    Barricarte, Aurelio
    Quirós, Jose Ramón
    Dorronsoro, Miren
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sternby, Hanna
    Bradbury, Kathryn E
    Wareham, Nick
    Riboli, Elio
    Gunter, Marc
    Brennan, Paul
    Duell, Eric J
    Ferrari, Pietro
    Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 4, p. 801-812Article in journal (Refereed)
    Abstract [en]

    Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.

  • 155. Nettleton, Jennifer A
    et al.
    Follis, Jack L
    Ngwa, Julius S
    Smith, Caren E
    Ahmad, Shafqat
    Tanaka, Toshiko
    Wojczynski, Mary K
    Voortman, Trudy
    Lemaitre, Rozenn N
    Kristiansson, Kati
    Nuotio, Marja-Liisa
    Houston, Denise K
    Perälä, Mia-Maria
    Qi, Qibin
    Sonestedt, Emily
    Manichaikul, Ani
    Kanoni, Stavroula
    Ganna, Andrea
    Mikkilä, Vera
    North, Kari E
    Siscovick, David S
    Harald, Kennet
    Mckeown, Nicola M
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rissanen, Harri
    Liu, Yongmei
    Lahti, Jari
    Hu, Frank B
    Bandinelli, Stefania
    Rukh, Gull
    Rich, Stephen
    Booij, Lisanne
    Dmitriou, Maria
    Ax, Erika
    Raitakari, Olli
    Mukamal, Kenneth
    Männistö, Satu
    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.
    Jula, Antti
    Ericson, Ulrika
    Jacobs, David R, Jr
    Van Rooij, Frank J A
    Deloukas, Panos
    Sjögren, Per
    Kähönen, Mika
    Djousse, Luc
    Perola, Markus
    Barroso, Inês
    Hofman, Albert
    Stirrups, Kathleen
    Viikari, Jorma
    Uitterlinden, André G
    Kalafati, Ioanna P
    Franco, Oscar H.
    Mozaffarian, Dariush
    Salomaa, Veikko
    Borecki, Ingrid B
    Knekt, Paul
    Kritchevsky, Stephen B
    Eriksson, Johan G
    Dedoussis, George V
    Qi, Lu
    Ferrucci, Luigi
    Orho-Melander, Marju
    Zillikens, M Carola
    Ingelsson, Erik
    Lehtimäki, Terho
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden.
    Cupples, L Adrienne
    Loos, Ruth J F
    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, Sweden; Department of Nutrition, Harvard Chan School of Public Health, Boston, MA, USA.
    Gene x dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry2015In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, no 16, p. 4728-4738Article in journal (Refereed)
    Abstract [en]

    Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

  • 156. Nettleton, Jennifer A.
    et al.
    Hivert, Marie-France
    Lemaitre, Rozenn N.
    McKeown, Nicola M.
    Mozaffarian, Dariush
    Tanaka, Toshiko
    Wojczynski, Mary K.
    Hruby, Adela
    Djousse, Luc
    Ngwa, Julius S.
    Follis, Jack L.
    Dimitriou, Maria
    Ganna, Andrea
    Houston, Denise K.
    Kanoni, Stavroula
    Mikkila, Vera
    Manichaikul, Ani
    Ntalla, Ioanna
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sonestedt, Emily
    van Rooij, Frank J. A.
    Bandinelli, Stefania
    de Koning, Lawrence
    Ericson, Ulrika
    Hassanali, Neelam
    Kiefte-de Jong, Jessica C.
    Lohman, Kurt K.
    Raitakari, Olli
    Papoutsakis, Constantina
    Sjogren, Per
    Stirrups, Kathleen
    Ax, Erika
    Deloukas, Panos
    Groves, Christopher J.
    Jacques, Paul F.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Liu, Yongmei
    McCarthy, Mark I.
    North, Kari
    Viikari, Jorma
    Zillikens, M. Carola
    Dupuis, Josee
    Hofman, Albert
    Kolovou, Genovefa
    Mukamal, Kenneth
    Prokopenko, Inga
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Seppala, Ilkka
    Cupples, L. Adrienne
    Hu, Frank B.
    Kahonen, Mika
    Uitterlinden, Andre G.
    Borecki, Ingrid B.
    Ferrucci, Luigi
    Jacobs, David R., Jr.
    Kritchevsky, Stephen B.
    Orho-Melander, Marju
    Pankow, James S.
    Lehtimaki, Terho
    Witteman, Jacqueline C. M.
    Ingelsson, Erik
    Siscovick, David S.
    Dedoussis, George
    Meigs, James B.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Meta-analysis investigating associations between healthy diet and fasting glucose and insulin levels and modification by loci associated with glucose homeostasis in data from 15 cohorts2013In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 177, no 2, p. 103-115Article, review/survey (Refereed)
    Abstract [en]

    Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 US and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG ( 0.004 mmol/L, 95 confidence interval: 0.005, 0.003) and FI ( 0.008 ln-pmol/L, 95 confidence interval: 0.009, 0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG- and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions.

  • 157. Nettleton, Jennifer A
    et al.
    McKeown, Nicola M
    Kanoni, Stavroula
    Lemaitre, Rozenn N
    Hivert, Marie-France
    Ngwa, Julius
    van Rooij, Frank J A
    Sonestedt, Emily
    Wojczynski, Mary K
    Ye, Zheng
    Tanaka, Toshiko
    Garcia, Melissa
    Anderson, Jennifer S
    Follis, Jack L
    Djousse, Luc
    Mukamal, Kenneth
    Papoutsakis, Constantina
    Mozaffarian, Dariush
    Zillikens, M Carola
    Bandinelli, Stefania
    Bennett, Amanda J
    Borecki, Ingrid B
    Feitosa, Mary F
    Ferrucci, Luigi
    Forouhi, Nita G
    Groves, Christopher J
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Harris, Tamara
    Hofman, Albert
    Houston, Denise K
    Hu, Frank B
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Kritchevsky, Stephen B
    Langenberg, Claudia
    Launer, Lenore
    Liu, Yongmei
    Loos, Ruth J
    Nalls, Michael
    Orho-Melander, Marju
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rice, Kenneth
    Riserus, Ulf
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Rotter, Jerome I
    Saylor, Georgia
    Sijbrands, Eric JG
    Sjögren, Per
    Smith, Albert
    Steingrímsdóttir, Laufey
    Uitterlinden, André G
    Wareham, Nicholas J
    Prokopenko, Inga
    Pankow, James S
    van Duijn, Cornelia M
    Flores, Jose C
    Witteman, Jaqueline CM
    Dupuis, Josée
    Dedoussis, George V
    Ordovas, Jose M
    Ingelsson, Erik
    Cupples, L Adrienne
    Siscovick, David S
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Meigs, James B
    Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies2010In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, no 12, p. 2684-2691Article in journal (Refereed)
    Abstract [en]

    Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

  • 158.
    Neumann, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Cancer Epidemiology, University Cancer Center, University Hospital, Technische Universität Dresden, Germany.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Schoffer, Olaf
    Cancer Epidemiology, University Cancer Center, University Hospital, Technische Universität Dresden, Germany.
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Klug, Stefanie J.
    Cancer Epidemiology, University Cancer Center, University Hospital, Technische Universität Dresden, Germany.
    Lindholm, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Risk equations for the development of worsened glucose status and type 2 diabetes mellitus in a Swedish intervention program2013In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 13, article id 1014Article in journal (Refereed)
    Abstract [en]

    Background: Several studies investigated transitions and risk factors from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D). However, there is a lack of information on the probabilities to transit from normal glucose tolerance (NGT) to different pre-diabetic states and from these states to T2D. The objective of our study is to estimate these risk equations and to quantify the influence of single or combined risk factors on these transition probabilities. Methods: Individuals who participated in the VIP program twice, having the first examination at ages 30, 40 or 50 years of age between 1990 and 1999 and the second examination 10 years later were included in the analysis. Participants were grouped into five groups: NGT, impaired fasting glucose (IFG), IGT, IFG&IGT or T2D. Fourteen potential risk factors for the development of a worse glucose state (pre-diabetes or T2D) were investigated: sex, age, education, perceived health, triglyceride, blood pressure, BMI, smoking, physical activity, snus, alcohol, nutrition and family history. Analysis was conducted in two steps. Firstly, factor analysis was used to find candidate variables; and secondly, logistic regression was employed to quantify the influence of the candidate variables. Bootstrap estimations validated the models. Results: In total, 29 937 individuals were included in the analysis. Alcohol and perceived health were excluded due to the results of the factor analysis and the logistic regression respectively. Six risk equations indicating different impacts of different risk factors on the transition to a worse glucose state were estimated and validated. The impact of each risk factor depended on the starting or ending pre-diabetes state. High levels of triglyceride, hypertension and high BMI were the strongest risk factors to transit to a worsened glucose state. Conclusions: The equations could be used to identify individuals with increased risk to develop any of the three pre-diabetic states or T2D and to adapt prevention strategies.

  • 159. Nieters, Alexandra
    et al.
    Rohrmann, Sabine
    Becker, Nikolaus
    Linseisen, Jakob
    Ruediger, Thomas
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Allen, Naomi E
    Travis, Ruth C
    Bingham, Sheila
    Khaw, Kay-Tee
    Ardanaz, Eva
    Redondo, M L
    Basterrechea, Mikel
    Martinez, Carmen
    Tormo, María-José
    Rosso, Stefano
    Tagliabue, Giovanna
    Masala, Giovanna
    Mattiello, Amalia
    Tumino, Rosario
    Boeing, Heiner
    Bergmann, Manuela
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Peeters, Petra H
    Bueno-de-Mesquita, Bas
    Boffetta, Paolo
    Brennan, Paul
    Ferrari, Pietro
    Neasham, David
    Lund, Eiliv
    Berglund, Göran
    Manjer, Jonas
    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.
    Vineis, Paolo
    Riboli, Elio
    Smoking and Lymphoma Risk in the European Prospective Investigation into Cancer and Nutrition.2008In: Am J Epidemiol, ISSN 1476-6256Article in journal (Refereed)
    Abstract [en]

    Lymphomas are one of the few cancers that have been increasing in incidence over the past decades. So far, only a few established risk factors have been identified, including immunosuppression and viral infections. Recent evidence suggests etiologic heterogeneity of different lymphoma subtypes. Smoking may affect risk differently, depending on the lymphoma entity. The European Prospective Investigation into Cancer and Nutrition was used to study the role of smoking in the etiology of lymphomas and individual subtypes within a prospective study. Information on baseline and lifetime tobacco smoking by 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. During 3,567,410 person-years of follow-up, 1,371 lymphoma cases (1,304 non-Hodgkin's lymphomas and 67 Hodgkin's lymphomas) were identified. Relative risk for smokers at recruitment was more than twofold higher for Hodgkin's lymphoma (hazard ratio = 2.14, 95% confidence interval: 1.18, 3.87) but was not elevated for non-Hodgkin's lymphoma (hazard ratio = 1.06, 95% confidence interval: 0.94, 1.19) and individual B-cell non-Hodgkin's lymphoma subtypes. In this prospective study, smoking appeared to increase Hodgkin's lymphoma risk consistently in both genders, whereas B-cell non-Hodgkin's lymphoma risk was not associated. Future analysis should involve viral biomarkers and genetic susceptibility markers to elucidate potential mechanisms of smoking-induced carcinogenesis, particularly for Hodgkin's lymphoma.

  • 160.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Dahlgren, Lars
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Brustad, Magritt
    Sjölander, Per
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Diet and lifestyle of the Sami of southern Lapland in the 1930s - 1950s and today2011In: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 70, no 3, p. 301-318Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To describe the lifestyle of the Sami of southern Lapland 50 to 70 years ago in relation to the present-day Sami and non-Sami populations and, thereby, to provide a basis for future studies of culturally related determinants of health and illness.

    STUDY DESIGN: A qualitative analysis, and a quantitative comparison of Sami and non-Sami groups.

    METHODS: Semi-structured interviews were conducted with 20 elderly Sami concerning their parents' lifestyle and diet 50 to 70 years ago. Questionnaire data from 81 reindeer-herding Sami, 226 non-reindeer-herding Sami and 1,842 sex-, age- and geographically matched non-Sami from the population-based Västerbotten Intervention Project were analysed by non-parametric tests and partial least squares methodology.

    RESULTS: Surprisingly, fatty fish may have been more important than reindeer meat for the Sami of southern Lapland in the 1930s to 1950s, and it is still consumed more frequently by reindeer-herding Sami than nonreindeer-herding Sami and non-Sami. Other dietary characteristics of the historical Sami and present-day reindeer-herding Sami were higher intakes of fat, blood and boiled coffee, and lower intakes of bread, fibre and cultivated vegetables, compared with present-day non-Sami. Physical activity was also a part of the daily life of the Sami to a greater extent in the 1930s to 1950s than today. Sami men often worked far from home, while the women were responsible for fishing, farming, gardening (which was introduced in the 1930-1950 period), as well as housework and childcare.

    CONCLUSIONS: For studies investigating characteristic lifestyle elements of specific ethnic groups, the elements of greatest acknowledged cultural importance today (in this case reindeer meat) may not be of the most objective importance traditionally.

  • 161.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    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.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Consumption of filtered and boiled coffee and the risk of incident cancer: a prospective cohort study2010In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 21, no 10, p. 1533-1544Article in journal (Refereed)
    Abstract [en]

    Background  Despite potentially relevant chemical differences between filtered and boiled coffee, this study is the first to investigate consumption in relation to the risk of incident cancer.

    Methods  Subjects were from the Västerbotten Intervention Project (64,603 participants, including 3,034 cases), with up to 15 years of follow-up. Hazard ratios (HR) were calculated by multivariate Cox regression.

    Results  No associations were found for all cancer sites combined, or for prostate or colorectal cancer. For breast cancer, boiled coffee ≥4 versus <1 occasions/day was associated with a reduced risk (HR = 0.52, CI = 0.30–0.88, p trend = 0.247). An increased risk of premenopausal and a reduced risk of postmenopausal breast cancer were found for both total (HRpremenopausal = 1.69, CI = 0.96–2.98, p trend = 0.015, HRpostmenopausal = 0.60, CI = 0.39–0.93, p trend = 0.006) and filtered coffee (HRpremenopausal = 1.76, CI = 1.04–3.00, p trend = 0.045, HRpostmenopausal = 0.52, CI = 0.30–0.88, p trend = 0.045). Boiled coffee was positively associated with the risk of respiratory tract cancer (HR = 1.81, CI = 1.06–3.08, p trend = 0.084), a finding limited to men. Main results for less common cancer types included total coffee in renal cell cancer (HR = 0.30, CI = 0.11–0.79, p trend = 0.009) and boiled coffee in pancreas cancer (HR = 2.51 CI = 1.15–5.50, p trend = 0.006).

    Conclusion  These findings demonstrate, for the first time, the potential relevance of brewing method in investigations of coffee consumption and cancer risk, but they must be confirmed in future studies.

  • 162.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Winkvist, A
    Clinical Nutrition, University of Gothenburg.
    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 Odontology.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Low-carbohydrate, high-protein score and cancer incidence and mortality in a northern swedish population2011In: Abstract Book: 2011 European Multidisciplinary Cancer Congress, Oxford: Elsevier, 2011, Vol. 47, p. S249-S249Conference paper (Refereed)
  • 163.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Winkvist, Anna
    Göteborgs universitet.
    Brustad, Magritt
    Sentrum for Samisk helseforskning, Tromsö universitet.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    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.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    A traditional Sami diet score as a determinant of mortality in a general northern Swedish population2012In: International Journal of Circumpolar Health, ISSN 2242-3982, E-ISSN 2242-3982, Vol. 71, article id 18537Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To examine the relationship between "traditional Sami" dietary pattern and mortality in a general northern Swedish population.

    STUDY DESIGN: Population-based cohort study.

    METHODS: We examined 77,319 subjects from the Västerbotten Intervention Program (VIP) cohort. A traditional Sami diet score was constructed by adding 1 point for intake above the median level of red meat, fatty fish, total fat, berries and boiled coffee, and 1 point for intake below the median of vegetables, bread and fibre. Hazard ratios (HR) for mortality were calculated by Cox regression.

    RESULTS: Increasing traditional Sami diet scores were associated with slightly elevated all-cause mortality in men [Multivariate HR per 1-point increase in score 1.04 (95% CI 1.01-1.07), p=0.018], but not for women [Multivariate HR 1.03 (95% CI 0.99-1.07), p=0.130]. This increased risk was approximately equally attributable to cardiovascular disease and cancer, though somewhat more apparent for cardiovascular disease mortality in men free from diabetes, hypertension and obesity at baseline [Multivariate HR 1.10 (95% CI 1.01-1.20), p=0.023].

    CONCLUSIONS: A weak increased all-cause mortality was observed in men with higher traditional Sami diet scores. However, due to the complexity in defining a "traditional Sami" diet, and the limitations of our questionnaire for this purpose, the study should be considered exploratory, a first attempt to relate a "traditional Sami" dietary pattern to health endpoints. Further investigation of cohorts with more detailed information on dietary and lifestyle items relevant for traditional Sami culture is warranted.

  • 164.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Winkvist, Anna
    Göteborgs universitet.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, 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.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Low-carbohydrate, high-protein score and mortality in a northern Swedish population2012In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, no 6, p. 694-700Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVE: Long-term effects of carbohydrate-restricted diets are unclear. We examined a low-carbohydrate, high-protein (LCHP) score in relation to mortality.

    SUBJECTS/METHODS: This is a population-based cohort study on adults in the northern Swedish county of Vasterbotten. In 37 639 men (1460 deaths) and 39 680 women (923 deaths) from the population-based Vasterbotten Intervention Program, deciles of energy-adjusted carbohydrate (descending) and protein (ascending) intake were added to create an LCHP score (2-20 points). Sex-specific hazard ratios (HR) were calculated by Cox regression.

    RESULTS: Median intakes of carbohydrates, protein and fat in subjects with LCHP scores 2-20 ranged from 61.0% to 38.6%, 11.3% to 19.2% and 26.6% to 41.5% of total energy intake, respectively. High LCHP score (14-20 points) did not predict all-cause mortality compared with low LCHP score (2-8 points), after accounting for saturated fat intake and established risk factors (men: HR for high vs low 1.03 (95% confidence interval (CI) 0.88-1.20), P for continuous 0.721; women: HR for high vs low 1.10 (95% CI 0.91-1.32), P for continuous 0.229). For cancer and cardiovascular disease, no clear associations were found. Carbohydrate intake was inversely associated with all-cause mortality, though only statistically significant in women (multivariate HR per decile increase 0.95 (95% CI 0.91-0.99), P = 0.010).

    CONCLUSION: Our results do not support a clear, general association between LCHP score and mortality. Studies encompassing a wider range of macronutrient consumption may be necessary to detect such an association.

  • 165.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Winkvist, Anna
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Dairy Products and Cancer Risk in a Northern Sweden Population2019In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914Article in journal (Refereed)
    Abstract [en]

    The role of dairy products in cancer is unclear. We assessed consumption of fermented milk, non-fermented milk, cheese, and butter, estimated from semi-quantitative food frequency questionnaires, in relation to prospective risk of breast, prostate, colorectal, smoking-, and obesity-related cancers in 101,235 subjects, including 12,552 cancer cases, in the population-based Northern Sweden Health and Disease Study. Most analyses (n = 20) rendered null results. In men, we observed an increased prostate cancer risk among high-consumers of cheese (hazard ratio (HR) for highest vs. lowest quintile (Q5-Q1), 1.11; 95% CI, 0.97-1.27; Ptrend = 0.013). In women, high-consumers of cheese had a decreased risk of overall cancer (HR Q5-Q1, 0.95; 95% CI, 0.88-1.04; Ptrend = 0.039), smoking-related (HR Q5-Q1, 0.84; 95% CI, 0.72-0.97; Ptrend ≤ 0.001), and colorectal cancers (HR Q5-Q1, 0.82; 95% CI, 0.63-1.07; Ptrend = 0.048). Butter yielded a weak decreased obesity-related cancer risk in women (HR Q5-Q1, 0.91; 95% CI, 0.81-1.02; Ptrend = 0.049). Fermented milk yielded HRs below zero in women, but with no clear linear associations. In conclusion, this study does not support any major adverse or beneficial effects of fermented milk, non-fermented milk, cheese, and butter in the diet from a cancer risk perspective.

  • 166.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Winkvist, Anna
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, SE-40530 Gothenburg, Sweden.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Low-carbohydrate, high-protein diet score and risk of incident cancer: a prospective cohort study2013In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 12, p. 58-Article in journal (Refereed)
    Abstract [en]

    Background: Although carbohydrate reduction of varying degrees is a popular and controversial dietary trend, potential long-term effects for health, and cancer in specific, are largely unknown. Methods: We studied a previously established low-carbohydrate, high-protein (LCHP) score in relation to the incidence of cancer and specific cancer types in a population-based cohort in northern Sweden. Participants were 62,582 men and women with up to 17.8 years of follow-up (median 9.7), including 3,059 prospective cancer cases. Cox regression analyses were performed for a LCHP score based on the sum of energy-adjusted deciles of carbohydrate (descending) and protein (ascending) intake labeled 1 to 10, with higher scores representing a diet lower in carbohydrates and higher in protein. Important potential confounders were accounted for, and the role of metabolic risk profile, macronutrient quality including saturated fat intake, and adequacy of energy intake reporting was explored. Results: For the lowest to highest LCHP scores, 2 to 20, carbohydrate intakes ranged from median 60.9 to 38.9% of total energy intake. Both protein (primarily animal sources) and particularly fat (both saturated and unsaturated) intakes increased with increasing LCHP scores. LCHP score was not related to cancer risk, except for a non-dose-dependent, positive association for respiratory tract cancer that was statistically significant in men. The multivariate hazard ratio for medium (9-13) versus low (2-8) LCHP scores was 1.84 (95% confidence interval: 1.05-3.23; p-trend = 0.38). Other analyses were largely consistent with the main results, although LCHP score was associated with colorectal cancer risk inversely in women with high saturated fat intakes, and positively in men with higher LCHP scores based on vegetable protein. Conclusion: These largely null results provide important information concerning the long-term safety of moderate carbohydrate reduction and consequent increases in protein and, in this cohort, especially fat intakes. In order to determine the effects of stricter carbohydrate restriction, further studies encompassing a wider range of macronutrient intakes are warranted.

  • 167.
    Nordlund, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Källestål, Carina
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Ericson, Thorild
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling2009In: BMC Oral Health, ISSN 1472-6831, E-ISSN 1472-6831, Vol. 9, no 28Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dental caries is a chronic disease with plaque bacteria, diet and saliva modifying disease activity. Here we have used the PLS method to evaluate a multiplicity of such biological variables (n=88) for ability to predict caries in a cross-sectional (baseline caries) and prospective (2-year caries development) setting. METHODS: Multivariate PLS modelling was used to associate the many biological variables with caries recorded in thirty 14-year-old children by measuring the numbers of incipient and manifest caries lesions at all surfaces. RESULTS: A wide but shallow gliding scale of one fifth caries promoting or protecting, and four fifths non-influential, variables occurred. The influential markers behaved in the order of plaque bacteria > diet > saliva, with previously known plaque bacteria/diet markers and a set of new protective diet markers. A differential variable patterning appeared for new versus progressing lesions. The influential biological multimarkers (n=18) predicted baseline caries better (ROC area 0.96) than five markers (0.92) and a single lactobacilli marker (0.7) with sensitivity/specificity of 1.87, 1.78 and 1.13 at 1/3 of the subjects diagnosed sick, respectively. Moreover, biological multimarkers (n=18) explained 2-year caries increment slightly better than reported before but predicted it poorly (ROC area 0.76). By contrast, multimarkers based on previous caries predicted alone (ROC area 0.88), or together with biological multimarkers (0.94), increment well with a sensitivity/specificity of 1.74 at 1/3 of the subjects diagnosed sick. CONCLUSION: Multimarkers behave better than single-to-five markers but future multimarker strategies will require systematic searches for improved saliva and plaque bacteria markers.

  • 168. Norlén, P
    et al.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Birkhed, D
    Impact of medical and life-style factors on number of teeth in 68-year-old men in southern Sweden1996In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 54, no 1, p. 66-74Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate the impact of general health and life-style factors on the number of remaining teeth in 68-year-old men living in the city of Malmö, Sweden. The study included 483 men (participation rate, 78%). Poor self-assessed health, frequent medical attendance, diabetes, and oral dryness were related to fewer remaining teeth. Number of teeth was negatively correlated to concentrations of triglycerides and alkaline phosphatases in serum and to glucose in blood but positively correlated to serum urea. Various dietary variables including consumption of sucrose-containing products and nutritional quality were not related either to number of teeth or to prevalence of edentulousness. Smoking and high consumption of coffee or alcohol were associated with fewer remaining teeth. Multiple logistic regression analyses showed that social class, frequency of dental attendance, smoking, and serum concentrations of triglycerides and urea had an independent effect on number of teeth.

  • 169. Nyholm, Maria
    et al.
    Lissner, Lauren
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    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.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Winkvist, Anna
    Exploring dietary patterns, obesity and sources of bias: the Västerbotten Intervention Programme (VIP)2013In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 16, no 4, p. 631-638Article in journal (Refereed)
    Abstract [en]

    Objective: Dietary patterns capture the overall diet and thereby provide information on how nutrients are consumed in combinations, and have been suggested to be a better method than studying single nutrients. The present study explored the relationship between dietary patterns at baseline and incidence of obesity at 10-year follow-up in women.

    Design: A longitudinal study using baseline measurements from 1992-1996, including food intake, medication, heredity, socio-economic status, lifestyle and measured body composition, and follow-up data collected in 2002-2006 including measured body composition.

    Setting: Data from the Västerbotten Intervention Programme (VIP) in Sweden.

    Subjects: A total of 6545 initially non-obese women aged 30-50 years.

    Results: Among women reporting plausible energy intakes, the 'Fruit and vegetables cluster' predicted the highest incidence of obesity (OR = 1·76, 95 % CI 1·11, 2·76; P = 0·015) compared with women in the other food pattern groups combined. When adjusting for metabolic factors and BMI at baseline, the risk for obesity in the 'Fruit and vegetables cluster' was attenuated to non-significance. In contrast, high intake of fruit per se was associated with a decreased risk of developing obesity (OR = 0·69, 95 % CI 0·51, 0·91; P = 0·010).

    Conclusions: Dietary pattern groups identified by cluster analysis are likely to reflect characteristics in addition to diet, including lifestyle, previous and current health status and risk factors for future disease, whereas intake of fruit per se was a stable indicator and less affected by baseline characteristics. These results underscore the need for complementary methods in understanding diet-disease relationships.

  • 170. Nöthlings, Ute
    et al.
    Schulze, Matthias B
    Weikert, Cornelia
    Boeing, Heiner
    van der Schouw, Yvonne T
    Bamia, Christina
    Benetou, Vasiliki
    Lagiou, Pagona
    Krogh, Vittorio
    Beulens, Joline W J
    Peeters, Petra H M
    Halkjaer, Jytte
    Tjønneland, Anne
    Tumino, Rosario
    Panico, Salvatore
    Masala, Giovanna
    Clavel-Chapelon, Francoise
    de Lauzon, Blandine
    Boutron-Ruault, Marie-Christine
    Vercambre, Marie-Noël
    Kaaks, Rudolf
    Linseisen, Jakob
    Overvad, Kim
    Arriola, Larraitz
    Ardanaz, Eva
    Gonzalez, Carlos A
    Tormo, Marie-Jose
    Bingham, Sheila
    Khaw, Kay-Tee
    Key, Tim J A
    Vineis, Paolo
    Riboli, Elio
    Ferrari, Pietro
    Boffetta, Paolo
    Bueno-de-Mesquita, H Bas
    van der A, Daphne L
    Berglund, Göran
    Wirfält, Elisabet
    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
    Trichopoulo, Antonia
    Intake of vegetables, legumes, and fruit, and risk for all-cause, cardiovascular, and cancer mortality in a European diabetic population.2008In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 138, no 4, p. 775-81Article in journal (Refereed)
  • 171. Orfanos, Philippos
    et al.
    Naska, Androniki
    Trichopoulos, Dimitrios
    Slimani, Nadia
    Ferrari, Pietro
    van Bakel, Marit
    Deharveng, Genevieve
    Overvad, Kim
    Tjønneland, Anne
    Halkjær, Jytte
    Santucci de Magistris, Maria
    Tumino, Rosario
    Pala, Valeria
    Sacerdote, Carlotta
    Masala, Giovanna
    Skeie, Guri
    Engeset, Dagrun
    Lund, Eiliv
    Jakszyn, Paula
    Barricarte, Aurelio
    Chirlaque, Maria-Dolores
    Martinez-Garcia, Carmen
    Amiano, Pilar
    Quirós, J Ramon
    Bingham, Sheila
    Welch, Ailsa
    Spencer, Elizabeth A
    Key, Timothy J
    Rohrmann, Sabine
    Linseisen, Jakob
    Ray, Jennifer
    Boeing, Heiner
    Peeters, Petra H
    Bueno-de-Mesquita, H Bas
    Ocke, Marga
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, Gerd
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Berglund, Göran
    Manjer, Jonas
    Boutron-Ruault, Marie-Christine
    Touvier, Mathilde
    Clavel-Chapelon, Françoise
    Trichopoulou, Antonia
    Eating out of home and its correlates in 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) study.2007In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 10, no 12, p. 1515-1525Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare the average out-of-home (OH) consumption of foods and beverages, as well as energy intake, among populations from 10 European countries and to describe the characteristics of substantial OH eaters, as defined for the purpose of the present study, in comparison to other individuals. DESIGN: Cross-sectional study. Dietary data were collected through single 24-hour dietary recalls, in which the place of consumption was recorded. For the present study, substantial OH eaters were defined as those who consumed more than 25% of total daily energy intake at locations other than the household premises. Mean dietary intakes and the proportion of substantial OH eaters are presented by food group and country. Logistic regression analyses were used to estimate the odds of being a substantial OH eater in comparison to not being one, using mutually adjusted possible non-dietary determinants. SETTING: Ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: The subjects were 34 270 individuals, 12 537 men and 21 733 women, aged 35-74 years. RESULTS: The fraction of energy intake during OH eating was generally higher in northern European countries than in the southern ones. Among the food and beverage groups, those selectively consumed outside the home were coffee/tea/waters and sweets and, to a lesser extent, cereals, meats, added lipids and vegetables. Substantial OH eating was positively associated with energy intake and inversely associated with age and physical activity. Substantial OH eating was less common among the less educated compared with the more educated, and more common during weekdays in central and north Europe and during the weekend in south Europe. CONCLUSIONS: Eating outside the home was associated with sedentary lifestyle and increased energy intake; it was more common among the young and concerned in particular coffee/tea/waters and sweets.

  • 172.
    Ou, Gangwei
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hedberg, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hörstedt, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Baranov, Vladimir
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Forsberg, Göte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Drobni, Mirva
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease2009In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 104, no 12, p. 3058-3067Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Alterations in the composition of the microbiota in the intestine may promote development of celiac disease (CD). Using scanning electron microscopy (SEM) we previously demonstrated that rod-shaped bacteria were present on the epithelium of proximal small intestine in children with CD but not in controls. In this study we characterize the microbiota of proximal small intestine in children with CD and controls and identify CD-associated rod-shaped bacteria. METHODS: Proximal small intestine biopsies from 45 children with CD and 18 clinical controls were studied. Bacteria were identified by 16S rDNA sequencing in DNA extracted from biopsies washed with buffer containing dithiothreitol to enrich bacteria adhering to the epithelial lining, by culture-based methods and by SEM and transmission electron microscopy. RESULTS: The normal, mucosa-associated microbiota of proximal small intestine was limited. It was dominated by the genera Streptococcus and Neisseria, and also contained Veillonella, Gemella, Actinomyces, Rothia, and Haemophilus. The proximal small intestine microbiota in biopsies from CD patients collected during 2004-2007 differed only marginally from that of controls, and only one biopsy (4%) had rod-shaped bacteria by SEM (SEM+). In nine frozen SEM+ CD biopsies from the previous study, microbiotas were significantly enriched in Clostridium, Prevotella, and Actinomyces compared with SEM- biopsies. Bacteria of all three genera were isolated from children born during the Swedish CD epidemic. New Clostridium and Prevotella species and Actinomyces graevenitzii were tentatively identified. CONCLUSIONS: Rod-shaped bacteria, probably of the indicated species, constituted a significant fraction of the proximal small intestine microbiota in children born during the Swedish CD epidemic and may have been an important risk factor for CD contributing to the fourfold increase in disease incidence in children below 2 years of age during that time.

  • 173. Peagler, FD
    et al.
    Redman, RS
    NcNutt, RL
    Kruse, DH
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Enzyme histochemical and immunohistochemical localization of carbonic anhydrase as a marker of ductal differentiation in the developing rat parotid gland.1998In: Anatomical Record, ISSN 0003-276X, E-ISSN 1097-0185, Vol. 250, no 2, p. 190-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Carbonic anhydrase has been localized to the acini and ducts of mature rat parotid glands. This enzyme has been associated with ion transport, a prominent function of striated and excretory ducts in salivary glands, suggesting that it might be used as a marker of ductal differentiation. The purpose of this study was histochemically to document developmental changes in carbonic anhydrase in the ducts of the rat parotid gland. METHODS: Parotid glands were excised from rats at representative developmental ages. Enzyme histochemistry was done on frozen sections fixed in acetone, and immunohistochemistry was performed with antibodies to human carbonic anhydrase isoenzymes I, II, and VI on paraffin sections of glands fixed in Helly's fluid. RESULTS: Carbonic anhydrase activity was weak until age 21 days after birth, when it had increased slightly in the acini and intercalated ducts and moderately in striated and excretory ducts. The adult pattern was attained by 28 days, in which reactions were moderate to strong in the striated and excretory ducts and modest in the acini and intercalated ducts. Immunohistochemical reactions were weak until 14 days, then increased rapidly, and by 28 days approached the adult pattern of virtually none in the acini and modest to moderately strong in the striated and excretory ducts. The order of reaction intensity of the antibodies was II > I > VI. CONCLUSIONS: Carbonic anhydrase is a useful marker of the functional differentiation of the striated and excretory ducts of the developing rat parotid gland.

  • 174. Poveda, Alaitz
    et al.
    Chen, Yan
    Brändström, Anders
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Engberg, Elisabeth
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Clinical Research Centre, Lund University, Jan Waldenströms gata 35, Building 91, Skåne University Hospital, SE-20502 Malmö, Sweden.
    Kurbasic, Azra
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Clinical Research Centre, Lund University, Jan Waldenströms gata 35, Building 91, Skåne University Hospital, SE-20502 Malmö, Sweden; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
    The heritable basis of gene-environment interactions in cardiometabolic traits2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 3, p. 442-452Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Little is known about the heritable basis of gene-environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype-environment interactions.

    Methods Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software.

    Results All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h (2)) ranging from 24% to 47%. Genotype-environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype-age interactions for weight and systolic BP, genotype-sex interactions for BMI and triacylglycerols and genotype-alcohol intake interactions for weight remained significant after multiple test correction.

    Conclusion/hypothesis Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease.

  • 175. Poveda, Alaitz
    et al.
    Koivula, Robert W.
    Ahmad, Shafqat
    Barroso, Ines
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Renstrom, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmö, Sweden.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 3, p. 462-471Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis We compared the ability of genetic (established type 2 diabetes, fasting glucose, 2 h glucose and obesity variants) and modifiable lifestyle (diet, physical activity, smoking, alcohol and education) risk factors to predict incident type 2 diabetes and obesity in a population-based prospective cohort of 3,444 Swedish adults studied sequentially at baseline and 10 years later. Methods Multivariable logistic regression analyses were used to assess the predictive ability of genetic and lifestyle risk factors on incident obesity and type 2 diabetes by calculating the AUC. Results The predictive accuracy of lifestyle risk factors was similar to that yielded by genetic information for incident type 2 diabetes (AUC 75% and 74%, respectively) and obesity (AUC 68% and 73%, respectively) in models adjusted for age, age2 and sex. The addition of genetic information to the lifestyle model significantly improved the prediction of type 2 diabetes (AUC 80%; p = 0.0003) and obesity (AUC 79%; p < 0.0001) and resulted in a net reclassification improvement of 58% for type 2 diabetes and 64% for obesity. Conclusions/interpretation These findings illustrate that lifestyle and genetic information separately provide a similarly high degree of long-range predictive accuracy for obesity and type 2 diabetes.

  • 176. Prakobphol, A
    et al.
    Xu, F
    Hoang, VM
    Larsson, T
    Bergström, J
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Frängsmyr, L
    Holmskov, U
    Leffler, H
    Nilsson, C
    Borén, Thomas
    Wright, JR
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Fisher, SJ
    Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340.2000In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 275, no 51, p. 39860-6Article in journal (Refereed)
    Abstract [en]

    Salivary agglutinin is a high molecular mass component of human saliva that binds Streptococcus mutans, an oral bacterium implicated in dental caries. To study its protein sequence, we isolated the agglutinin from human parotid saliva. After trypsin digestion, a portion was analyzed by matrix-assisted laser/desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), which gave the molecular mass of 14 unique peptides. The remainder of the digest was subjected to high performance liquid chromatography, and the separated peptides were analyzed by MALDI-TOF/post-source decay; the spectra gave the sequences of five peptides. The molecular mass and peptide sequence information showed that salivary agglutinin peptides were identical to sequences in lung (lavage) gp-340, a member of the scavenger receptor cysteine-rich protein family. Immunoblotting with antibodies that specifically recognized either lung gp-340 or the agglutinin confirmed that the salivary agglutinin was gp-340. Immunoblotting with an antibody specific to the sialyl Le(x) carbohydrate epitope detected expression on the salivary but not the lung glycoprotein, possible evidence of different glycoforms. The salivary agglutinin also interacted with Helicobacter pylori, implicated in gastritis and peptic ulcer disease, Streptococcus agalactiae, implicated in neonatal meningitis, and several oral commensal streptococci. These results identify the salivary agglutinin as gp-340 and suggest it binds bacteria that are important determinants of either the oral ecology or systemic diseases.

  • 177. Prinelli, Federica
    et al.
    Fratiglioni, Laura
    Kalpouzos, Gregoria
    Musicco, Massimo
    Adorni, Fulvio
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Marseglia, Anna
    Xu, Weili
    Specific nutrient patterns are associated with higher structural brain integrity in dementia-free older adults2019In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 199, p. 281-288Article in journal (Refereed)
    Abstract [en]

    Optimal nutrition may play a beneficial role in maintaining a healthy brain. However, the relationship between nutrient intake and brain integrity is largely unknown. We investigated the association of specific nutrient dietary patterns with structural characteristics of the brain. Within the population-based Swedish National study on Aging and Care-Kungsholmen (SNAC-K), a cross-sectional study of 417 dementia-free participants aged >= 60 years who underwent structural magnetic resonance imaging (MRI) scans during 2001-2003, was carried-out. Data on dietary intake were collected using a food frequency questionnaire, from which intake of 21 nutrients was estimated. By principal component analysis, five nutrient patterns were extracted: (1) NP1 was characterized by fiber, vitamin C, E, beta-carotene, and folate [Fiber&Antioxidants], (2) NP2 by eicosapentaenoic (EPA, 20:5 omega-3) and docosahexaenoic (DHA, 22:6 omega-3) polyunsaturated fatty acids (PUFAs), proteins, cholesterol, vitamin B3, B12, and D [long chain (LC) omega-3PUFAs&Proteins], (3) NP3 by alpha-linoleic (18:2 omega-6) and alpha-linolenic (18:3 omega-3) PUFAs, monounsaturated fatty acids (MUFAs), and vitamin E [MUFAs &omega-3,6PUFAs], (4) NP4 by saturated fatty acids (SFAs), trans fats, MUFAs, and cholesterol [SFAs&Trans fats], (5) NP5 by B-vitamins, retinol, and proteins [B-Vitamins&Retinol]. Nutrient patterns scores were tertiled with the lowest tertile as reference, and were related to total brain volume (TBV) and white matter hyperintensities volume (WMHV) using linear regression models adjusting for potential confounders. In the multi-adjusted model, compared to the lowest intake for each pattern, the highest intake of NP1 (beta = 11.11, P = 0.009), NP2 (beta = 7.47, P = 0.052), and NP3 (beta = 10.54, P = 0.005) was associated with larger TBV whereas NP5 was related to smaller TBV (beta = -12.82, P = 0.001). The highest intake of NP1 was associated with lower WMHV (beta = -0.32, P = 0.049), whereas NP4 was associated with greater WMHV (beta = 0.31, P = 0.036). In sum, our results suggest that the identified brain-health specific nutrient combinations characterized by higher intake of fruit, vegetables, legumes, olive and seed oils, fish, lean red meat, poultry and low in milk and dairy products, cream, butter, processed meat and offal, were strongly associated with greater brain integrity among older adults.

  • 178.
    Qi, Qibin
    et al.
    Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA.
    Kilpeläinen, Tuomas O
    Downer, Mary K
    Tanaka, Toshiko
    Smith, Caren E
    Sluijs, Ivonne
    Sonestedt, Emily
    Chu, Audrey Y
    Renström, Frida
    Lin, Xiaochen
    Angquist, Lars H
    Huang, Jinyan
    Liu, Zhonghua
    Li, Yanping
    Asif Ali, Muhammad
    Xu, Min
    Ahluwalia, Tarunveer Singh
    Boer, Jolanda M A
    Chen, Peng
    Daimon, Makoto
    Eriksson, Johan
    Perola, Markus
    Friedlander, Yechiel
    Gao, Yu-Tang
    Heppe, Denise H M
    Holloway, John W
    Houston, Denise K
    Kanoni, Stavroula
    Kim, Yu-Mi
    Laaksonen, Maarit A
    Jääskeläinen, Tiina
    Lee, Nanette R
    Lehtimäki, Terho
    Lemaitre, Rozenn N
    Lu, Wei
    Luben, Robert N
    Manichaikul, Ani
    Männistö, Satu
    Marques-Vidal, Pedro
    Monda, Keri L
    Ngwa, Julius S
    Perusse, Louis
    van Rooij, Frank J A
    Xiang, Yong-Bing
    Wen, Wanqing
    Wojczynski, Mary K
    Zhu, Jingwen
    Borecki, Ingrid B
    Bouchard, Claude
    Cai, Qiuyin
    Cooper, Cyrus
    Dedoussis, George V
    Deloukas, Panos
    Ferrucci, Luigi
    Forouhi, Nita G
    Hansen, Torben
    Christiansen, Lene
    Hofman, Albert
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Jørgensen, Torben
    Karasawa, Shigeru
    Khaw, Kay-Tee
    Kim, Mi-Kyung
    Kristiansson, Kati
    Li, Huaixing
    Lin, Xu
    Liu, Yongmei
    Lohman, Kurt K
    Long, Jirong
    Mikkilä, Vera
    Mozaffarian, Dariush
    North, Kari
    Pedersen, Oluf
    Raitakari, Olli
    Rissanen, Harri
    Tuomilehto, Jaakko
    van der Schouw, Yvonne T
    Uitterlinden, André G
    Carola Zillikens, M
    Franco, Oscar H
    Shyong Tai, E
    Ou Shu, Xiao
    Siscovick, David S
    Toft, Ulla
    Monique Verschuren, W M
    Vollenweider, Peter
    Wareham, Nicholas J
    Witteman, Jacqueline C M
    Zheng, Wei
    Ridker, Paul M
    Kang, Jae H
    Liang, Liming
    Jensen, Majken K
    Curhan, Gary C
    Pasquale, Louis R
    Hunter, David J
    Mohlke, Karen L
    Uusitupa, Matti
    Adrienne Cupples, L
    Rankinen, Tuomo
    Orho-Melander, Marju
    Wang, Tao
    Chasman, Daniel I
    Franks, Paul
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA; Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA; Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
    Sørensen, Thorkild I A
    Hu, Frank B
    Loos, Ruth J F
    Nettleton, Jennifer A
    Qi, Lu
    FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals2014In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, no 25, p. 6961-6972Article in journal (Refereed)
    Abstract [en]

    FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

  • 179. Ramne, Stina
    et al.
    Dias, Joana Alves
    González-Padilla, Esther
    Olsson, Kjell
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Engström, Gunnar
    Ericson, Ulrika
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sonestedt, Emily
    Association between added sugar intake and mortality is nonlinear and dependent on sugar source in 2 Swedish population-based prospective cohorts2019In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, no 2, p. 411-423Article in journal (Refereed)
    Abstract [en]

    Background: Although sugar consumption has been associated with several risk factors for cardiometabolic diseases, evidence for harmful long-term effects is lacking. In addition, most studies have focused on sugar-sweetened beverages (SSBs), not sugar per se.

    Objective: The aim of this study was to examine the associations between added and free sugar intake, intake of different sugar sources, and mortality risk.

    Methods: Two prospective population-based cohorts were examined: the Malmö Diet and Cancer Study (MDCS; n = 24,272), which collected dietary data by combining a food diary, interview, and food-frequency questionnaire (FFQ), and the Northern Swedish Health and Disease Study (NSHDS; n = 24,475), which assessed diet with an FFQ. Sugar intakes defined as both added and free sugar and different sugar sources were examined. The associations with mortality were examined using a multivariable Cox proportional hazards regression.

    Results: Higher sugar consumption was associated with a less favorable lifestyle in general. The lowest mortality risk was found with added sugar intakes between 7.5% and 10% of energy (E%) intake in both cohorts. Intakes >20E% were associated with a 30% increased mortality risk, but increased risks were also found at intakes <5E% [23% in the MDCS and 9% (nonsignificant) in the NSHDS]. Similar U-shaped associations were found for both cardiovascular and cancer mortality in the MDCS. By separately analyzing the different sugar sources, the intake of SSBs was positively associated with mortality, whereas the intake of treats was inversely associated.

    Conclusions: Our findings indicate that a high sugar intake is associated with an increased mortality risk. However, the risk is also increased among low sugar consumers, although they have a more favorable lifestyle in general. In addition, the associations are dependent on the type of sugar source.

  • 180. Redman, RS
    et al.
    Peagler, FD
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Immunohistochemical localization of carbonic anhydrases I, II, and VI in the developing rat sublingual and submandibular glands.2000In: Anatomical Record, ISSN 0003-276X, E-ISSN 1097-0185, Vol. 258, no 3, p. 269-276Article in journal (Refereed)
    Abstract [en]

    Carbonic anhydrase has been localized to the acini and ducts of mature rat salivary glands. This enzyme has been associated with ion transport, a prominent function of striated and excretory ducts in salivary glands, suggesting that it might be used as a marker of ductal differentiation. The purpose of this study was to immunohistochemically document developmental changes in carbonic anhydrase in the ducts of the rat sublingual and submandibular glands. Immunohistochemistry was performed with antibodies to human carbonic anhydrase isoenzymes I, II and VI on sections of sublingual and submandibular glands from rats at representative postnatal developmental ages. Reactions were weak in the ducts of both glands at 1 day, then progressively increased. By 42 days, reactions had the adult pattern of virtually none in the mucous or seromucous acini, moderate to strong in the striated and excretory ducts, and none to weak in the intercalated ducts. Weak to moderate reactions were observed in the granular convoluted tubules of the submandibular gland as they became recognizable at age 42 days. Reactions to carbonic anhydrase I and II antibodies also increased from none (1 day) to modest (42 days) in the demilunes of the sublingual gland. The order of reaction intensity of the antibodies was II > I > VI. When localized via these anti-human antibodies, carbonic anhydrase is a useful marker of the functional differentiation of the striated and excretory ducts of the developing rat sublingual and submandibular glands. Copyright 2000 Wiley-Liss, Inc.

  • 181.
    Renström, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. 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.
    Florez, Jose C
    Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hu, Frank B
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Genetic predisposition to long-term nondiabetic deteriorations in glucose homeostasis: Ten-year follow-up of the GLACIER study.2011In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, no 1, p. 345-54Article in journal (Refereed)
    Abstract [en]

    Our findings imply that genetic profiling might facilitate the early detection of persons who are genetically susceptible to deteriorating glucose control; studies of incident type 2 diabetes and discrete cardiovascular end points will help establish whether the magnitude of these changes is clinically relevant.

  • 182. Rohrmann, S.
    et al.
    Steinbrecher, A.
    Linseisen, J.
    Hermann, S.
    May, A.
    Luan, J.
    Ekelund, U.
    Overvad, K.
    Tjonneland, A.
    Halkjaer, J.
    Fagherazzi, G.
    Boutron-Ruault, M-C
    Clavel-Chapelon, F.
    Agnoli, C.
    Tumino, R.
    Masala, G.
    Mattiello, A.
    Ricceri, F.
    Travier, N.
    Amiano, P.
    Ardanaz, E.
    Chirlaque, M-D
    Sanchez, M-J
    Rodriguez, L.
    Nilsson, Lena Maria
    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.
    Hedblad, B.
    Rosvall, M.
    Lund, E.
    Braaten, T.
    Naska, A.
    Orfanos, P.
    Trichopoulou, A.
    van den Berg, S.
    Bueno-de-Mesquita, H. B.
    Bergmann, M. M.
    Steffen, A.
    Kaaks, R.
    Teucher, B.
    Wareham, N. J.
    Khaw, K-T
    Crowe, F. L.
    Illner, A-K
    Slimani, N.
    Gallo, V.
    Mouw, T.
    Norat, T.
    Peeters, P. H. M.
    The association of education with long-term weight change in the EPIC-PANACEA cohort2012In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, no 8, p. 957-963