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  • 1. Agogo, George O.
    et al.
    van der Voet, Hilko
    van 't Veer, Pieter
    Ferrari, Pietro
    Muller, David C.
    Sanchez-Cantalejo, Emilio
    Bamia, Christina
    Braaten, Tonje
    Knuppel, Sven
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    van Eeuwijk, Fred A.
    Boshuizen, Hendriek C.
    A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data2016In: BMC Medical Research Methodology, ISSN 1471-2288, E-ISSN 1471-2288, Vol. 16, article id 139Article in journal (Refereed)
    Abstract [en]

    Background: Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data. Methods: We proposed a method to adjust for the bias in the diet-disease association (hereafter, association), due to measurement error in dietary intake and a mismeasured confounder, when there is no internal validation data. The method combines prior information on the validity of the self-report instrument with the observed data to adjust for the bias in the association. We compared the proposed method with the method that ignores the confounder effect, and with the method that ignores measurement errors completely. We assessed the sensitivity of the estimates to various magnitudes of measurement error, error correlations and uncertainty in the literature-reported validation data. We applied the methods to fruits and vegetables (FV) intakes, cigarette smoking (confounder) and all-cause mortality data from the European Prospective Investigation into Cancer and Nutrition study. Results: Using the proposed method resulted in about four times increase in the strength of association between FV intake and mortality. For weakly correlated errors, measurement error in the confounder minimally affected the hazard ratio estimate for FV intake. The effect was more pronounced for strong error correlations. Conclusions: The proposed method permits sensitivity analysis on measurement error structures and accounts for uncertainties in the reported validity coefficients. The method is useful in assessing the direction and quantifying the magnitude of bias in the association due to measurement errors in the confounders.

  • 2. Agogo, George O.
    et al.
    van der Voet, Hilko
    van't Veer, Pieter
    Ferrari, Pietro
    Leenders, Max
    Muller, David C.
    Sanchez-Cantalejo, Emilio
    Bamia, Christina
    Braaten, Tonje
    Knueppel, Sven
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    van Eeuwijk, Fred A.
    Boshuizen, Hendriek
    Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design: EPIC Case Study2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e113160-Article in journal (Refereed)
    Abstract [en]

    In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted twopart regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.

  • 3. Agudo, Antonio
    et al.
    Bonet, Catalina
    Travier, Noemie
    Gonzalez, Carlos A.
    Vineis, Paolo
    Bueno-de-Mesquita, H. Bas
    Trichopoulos, Dimitrios
    Boffetta, Paolo
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Schuetze, Madlen
    Boeing, Heiner
    Tjonneland, Anne
    Halkjaer, Jytte
    Overvad, Kim
    Dahm, Christina C.
    Ramon Quiros, J.
    Sanchez, Maria-Jose
    Larranaga, Nerea
    Navarro, Carmen
    Ardanaz, Eva
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Key, Timothy J.
    Allen, Naomi E.
    Trichopoulou, Antonia
    Lagiou, Pagona
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Panico, Salvatore
    Boshuizen, Hendriek
    Buchner, Frederike L.
    Peeters, Petra H. M.
    Borgquist, Signe
    Almquist, Martin
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Gram, Inger T.
    Lund, Eiliv
    Weiderpass, Elisabete
    Romieu, Isabelle
    Riboli, Elio
    Impact of Cigarette Smoking on Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 36, p. 4550-4557Article in journal (Refereed)
    Abstract [en]

    Purpose Our aim was to assess the impact of cigarette smoking on the risk of the tumors classified by the International Agency for Research on Cancer as causally associated with smoking, referred to as tobacco-related cancers (TRC). Methods The study population included 441,211 participants (133,018 men and 308,193 women) from the European Prospective Investigation Into Cancer and Nutrition. We investigated 14,563 participants who developed a TRC during an average follow-up of 11 years. The impact of smoking cigarettes on cancer risk was assessed by the population attributable fraction (AF(p)), calculated using the adjusted hazard ratios and 95% CI for current and former smokers, plus either the prevalence of smoking among cancer cases or estimates from surveys in representative samples of the population in each country. Results The proportion of all TRC attributable to cigarette smoking was 34.9% (95% CI, 32.5 to 37.4) using the smoking prevalence among cases and 36.2% (95% CI, 33.7 to 38.6) using the smoking prevalence from the population. The AF(p) were above 80% for cancers of the lung and larynx, between 20% and 50% for most respiratory and digestive cancers and tumors from the lower urinary tract, and below 20% for the remaining TRC. Conclusion Using data on cancer incidence for 2008 and our AF(p) estimates, about 270,000 new cancer diagnoses per year can be considered attributable to cigarette smoking in the eight European countries with available data for both men and women (Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Sweden, Denmark). 

  • 4. Al-Delaimy, W K
    et al.
    Slimani, N
    Ferrari, P
    Key, T
    Spencer, E
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, G
    Mattisson, I
    Wirfalt, E
    Sieri, S
    Agudo, A
    Celentano, E
    Palli, D
    Sacerdote, C
    Tumino, R
    Dorronsoro, M
    Ocké, M C
    Bueno-De-Mesquita, H B
    Overvad, K
    Chirlaque, Ma D
    Trichopoulou, A
    Naska, A
    Tjonneland, A
    Olsen, A
    Lund, E
    Skeie, G
    Ardanaz, E
    Kesse, E
    Boutron-Ruault, M-C
    Clavel-Chapelon, F
    Bingham, S
    Welch, A A
    Martinez-Garcia, C
    Nagel, G
    Linseisen, J
    Quirós, J R
    Peeters, P H M
    van Gils, C H
    Boeing, H
    van Kappel, A L
    Steghens, J-P
    Riboli, E
    Plasma carotenoids as biomarkers of intake of fruits and vegetables: ecological-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).2005In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 59, no 12, p. 1397-408Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to assess the ability of a single 24-h dietary recall (24HDR) and food questionnaires (FQ) to predict plasma carotenoid levels at the ecological level by assessing the relationship between mean plasma carotenoid levels and mean intake of fruit and vegetables measured by 24HDR and FQ across 16 European regions. DESIGN: A random subsample of 3089 subjects was included, stratified by age and gender. They provided blood samples and dietary information between 1992 and 2000 as part of the European Prospective Investigation into Cancer and Nutrition. RESULTS: Using Spearman's correlation coefficients, the correlations between mean regional 24HDR fruit and vegetable variables and corresponding mean plasma carotenoid levels were generally higher than the correlations using FQ means. The highest correlation was between the 24HDR citrus fruit variable and beta-cryptoxanthin (r = 0.90). For 24HDR, total fruits and vegetables were highly correlated with lutein, zeaxanthin, and beta-cryptoxanthin (r = 0.83-0.87), while vegetables were more closely related with lutein (r = 0.69) and zeaxanthin (r = 0.68), and fruits correlated with zeaxanthin (r = 0.87) and beta-cryptoxanthin (r = 0.84). Root vegetables (r = 0.81) and total carrots (r = 0.71) were well correlated with alpha-carotene. In the multivariate models adjusting for age, body mass index, and season, and using observations of means stratified by sex and region, the association was generally higher for 24HDR compared to FQ. CONCLUSION: Mean regional intakes of fruits and vegetables in several European countries were closely correlated with corresponding mean plasma levels of individual carotenoids. Fruits and vegetables measured by 24HDR were generally better able to predict plasma carotenoids at the ecological level.

  • 5. Al-Delaimy, WK
    et al.
    Ferrari, P
    Slimani, N
    Pala, V
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Nilsson, S
    Mattisson, I
    Wirfalt, E
    Galasso, R
    Palli, D
    Vineis, P
    Tumino, R
    Dorronsoro, M
    Pera, G
    Ocké, MC
    Bueno-de-Mesquita, HB
    Overvad, K
    Chirlaque, M
    Trichopoulou, A
    Naska, A
    Tjonneland, A
    Olsen, A
    Lund, E
    Alsaker, EH
    Barricarte, A
    Kesse, E
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Key, TJ
    Spencer, E
    Bingham, S
    Welch, AA
    Sanchez-Perez, MJ
    Nagel, G
    Linseisen, J
    Quirós, JR
    Peeters, PH
    van Gils, CH
    Boeing, H
    van Kappel, AL
    Steghens, JP
    Riboli, E
    Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).2005In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 59, no 12, p. 1387-1396Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.

  • 6. Al-Delaimy, WK
    et al.
    Van Kappel, AL
    Ferrari, P
    Slimani, N
    Steghens, JP
    Bingham, S
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Wallström, P
    Overvad, K
    Tjonneland, A
    Key, TJ
    Welch, AA
    Bas Bueno-De-Mesquita, H
    Peeters, PH
    Boeing, H
    Linseisen, J
    Clavel-Chapelon, F
    Guibout, C
    Navarro, C
    Quiros, JR
    Palli, D
    Celentano, E
    Trichopoulou, A
    Benetou, V
    Kaaks, R
    Riboli, E
    Plasma levels of six carotenoids in nine European countries: report from the European Prospective Investigation into Cancer and Nutrition (EPIC).2004In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 7, no 6, p. 713-722Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet-disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe. OBJECTIVE: Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Plasma levels of six carotenoids--alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin--were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids. RESULTS: Mean plasma level of the sum of the six carotenoids varied twofold between regions (1.35 micromol l(-1) for men in Malmö, Sweden vs. 2.79 micromol l(-1) for men in Ragusa/Naples, Italy; 1.61 micromol l(-1) for women in The Netherlands vs. 3.52 micromol l(-1) in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (alpha-carotene: 0.06 micromol l(-1) for men in Murcia, Spain vs. 0.25 micromol l(-1) for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partial R(2)=27.3%), followed by BMI (partial R(2)=5.2%), gender (partial R(2)=2.7%) and smoking status (partial R(2)=2.8%). Females had higher total carotenoid levels than males across Europe. CONCLUSIONS: Plasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe.

  • 7. Aleksandrova, Krasimira
    et al.
    Pischon, Tobias
    Jenab, Mazda
    Bueno-de-Mesquita, H Bas
    Fedirko, Veronika
    Norat, Teresa
    Romaguera, Dora
    Knüppel, Sven
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Dartois, Laureen
    Kaaks, Rudolf
    Li, Kuanrong
    Tjønneland, Anne
    Overvad, Kim
    Quirós, José Ramón
    Buckland, Genevieve
    Sánchez, María José
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Bradbury, Kathryn E
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Siersema, Peter D
    Peeters, Petra HM
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ericson, Ulrika
    Ohlsson, Bodil
    Weiderpass, Elisabete
    Skeie, Guri
    Borch, Kristin
    Rinaldi, Sabina
    Romieu, Isabelle
    Kong, Joyce
    Gunter, Marc J
    Ward, Heather A
    Riboli, Elio
    Boeing, Heiner
    Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study2014In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, no 1, p. 168-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

  • 8. Assi, Nada
    et al.
    Moskal, Aurelie
    Slimani, Nadia
    Viallon, Vivian
    Chajes, Veronique
    Freisling, Heinz
    Monni, Stefano
    Knueppel, Sven
    Foerster, Jana
    Weiderpass, Elisabete
    Lujan-Barroso, Leila
    Amiano, Pilar
    Ardanaz, Eva
    Molina-Montes, Esther
    Salmeron, Diego
    Ramon Quiros, Jose
    Olsen, Anja
    Tjonneland, Anne
    Dahm, Christina C.
    Overvad, Kim
    Dossus, Laure
    Fournier, Agnes
    Baglietto, Laura
    Fortner, Renee Turzanski
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Bamia, Christina
    Orfanos, Philippos
    De Magistris, Maria Santucci
    Masala, Giovanna
    Agnoli, Claudia
    Ricceri, Fulvio
    Tumino, Rosario
    de Mesquita, H. Bas Bueno
    Bakker, Marije F.
    Peeters, Petra H. M.
    Skeie, Guri
    Braaten, Tonje
    Winkvist, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Key, Tim
    Travis, Ruth
    Schmidt, Julie A.
    Merritt, Melissa A.
    Riboli, Elio
    Romieu, Isabelle
    Ferrari, Pietro
    A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)2016In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 19, no 2, p. 242-254Article in journal (Refereed)
    Abstract [en]

    Objective Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. Design Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. Setting The European Prospective Investigation into Cancer and Nutrition (EPIC). Subjects Women (n 334 850) from the EPIC study. Results The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B-12 and D, while the second TT component (TC2) reflected a diet rich in -carotene, riboflavin, thiamin, vitamins C and B-6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=089, 95 % CI 083, 095, P-trend<001) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=089, 95 % CI 081, 098, P-trend=002) and progesterone receptor-positive tumours (HRQ5 v. Q1=087, 95 % CI 077, 098, P-trend<001). Conclusions TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.

  • 9. Bamia, C
    et al.
    Orfanos, P
    Ferrari, P
    Overvad, K
    Hundborg, HH
    Tjonneland, A
    Olsen, A
    Kesse, E
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Nagel, G
    Boffetta, P
    Boeing, H
    Hoffmann, K
    Trichopoulos, D
    Baibas, N
    Psaltopoulou, T
    Norat, T
    Slimani, N
    Palli, D
    Krogh, V
    Panico, S
    Tumino, R
    Sacerdote, C
    Bueno-de-Mesquita, HB
    Ocke, MC
    Peeters, PH
    van Rossum, CT
    Quiros, JR
    Sanchez, MJ
    Navarro, C
    Barricarte, A
    Dorronsoro, M
    Berglund, G
    Wirfalt, E
    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.
    Bingham, S
    Khaw, KT
    Spencer, EA
    Roddam, AW
    Riboli, E
    Trichopoulou, A
    Dietary patterns among older Europeans: the EPIC-Elderly study.2005In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 94, no 1, p. 100-13Article in journal (Refereed)
    Abstract [en]

    Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north-south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.

  • 10. Bamia, Christina
    et al.
    Trichopoulos, Dimitrios
    Ferrari, Pietro
    Overvad, Kim
    Bjerregaard, Lone
    Tjønneland, Anne
    Halkjaer, Jytte
    Clavel-Chapelon, Françoise
    Kesse, Emmanuelle
    Boutron-Ruault, Marie-Christine
    Boffetta, Paolo
    Nagel, Gabriele
    Linseisen, Jacob
    Boeing, Heiner
    Hoffmann, Kurt
    Kasapa, Christina
    Orfanou, Anastasia
    Travezea, Chrysoula
    Slimani, Nadia
    Norat, Teresa
    Palli, Domenico
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, H Bas
    Waijers, Patricia M C M
    Peeters, Petra H M
    van der Schouw, Yvonne T
    Berenguer, Antonio
    Martinez-Garcia, Carmen
    Navarro, Carmen
    Barricarte, Aurelio
    Dorronsoro, Miren
    Berglund, Göran
    Wirfält, Elisabet
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, Gerd
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Bingham, Sheila
    Khaw, Kay-Tee
    Spencer, Elizabeth A
    Key, Tim
    Riboli, Elio
    Trichopoulou, Antonia
    Dietary patterns and survival of older Europeans: the EPIC-Elderly Study (European Prospective Investigation into Cancer and Nutrition).2007In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 10, no 6, p. 590-8Article in journal (Refereed)
  • 11. Benetou, V
    et al.
    Orfanos, P
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Bergström, Ulrica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Berrino, F
    Tumino, R
    Borch, K B
    Lund, E
    Peeters, P H M
    Grote, V
    Li, K
    Altzibar, J M
    Key, T
    Boeing, H
    von Ruesten, A
    Norat, T
    Wark, P A
    Riboli, E
    Trichopoulou, A
    Mediterranean diet and incidence of hip fractures in a European cohort2013In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, no 5, p. 1587-1598Article in journal (Refereed)
    Abstract [en]

    Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

  • 12. Benetou, V
    et al.
    Orfanos, P
    Zylis, D
    Sieri, S
    Contiero, P
    Tumino, R
    Giurdanella, M C
    Peeters, P H M
    Linseisen, J
    Nieters, A
    Boeing, H
    Weikert, C
    Pettersson, U
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Bueno-de-Mesquita, H B
    Dorronsoro, M
    Boffetta, P
    Trichopoulou, A
    Diet and hip fractures among elderly Europeans in the EPIC cohort2011In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 65, no 1, p. 132-139Article in journal (Refereed)
    Abstract [en]

    In a prospective study of the elderly, diet, including consumption of dairy products, alcohol and vitamin D, did not appear to play a major role in hip fracture incidence. There is however, weak and statistically non-significant evidence that vegetable and fish consumption and intake of polyunsaturated lipids may have a beneficial, whereas saturated lipid intake a detrimental effect.

  • 13. Bergdahl, M
    et al.
    Bergdahl, J
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Depressive symptoms in individuals with idiopathic subjective dry mouth1997In: Journal of Oral Pathology & Medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, Vol. 26, no 10, p. 448-450Article in journal (Refereed)
    Abstract [en]

    It has been known for many centuries that there is a relationship between saliva flow rate and emotional status. The significance of psychological processes in the subjective sensation of a dry mouth has been discussed earlier, and this study deals with the presence of depressive symptoms in individuals with idiopathic subjective sensation of a dry mouth. Depressive symptoms in 94 healthy subjects with normal flow rates for unstimulated and stimulated whole saliva but with a subjective sensation of a dry mouth were assessed by the Beck Depression Inventory (BDI) and compared with healthy age- and gender-matched controls. The subjects with a subjective dry mouth condition were significantly more depressive and also had a significantly higher frequency of depressive symptoms. Depression was found in 21.3% of the individuals with a subjective dry mouth sensation and in 3.2% of the controls. The results of this study indicate that, in some cases, subjective dry mouth may be of psychological origin.

  • 14. Bhoo-Pathy, Nirmala
    et al.
    Peeters, Petra H. M.
    Uiterwaal, Cuno S. P. M.
    Bueno-de-Mesquita, H. Bas
    Bulgiba, Awang M.
    Bech, Bodil Hammer
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Perquier, Florence
    Teucher, Birgit
    Kaaks, Rudolf
    Schuetze, Madlen
    Boeing, Heiner
    Lagiou, Pagona
    Orfanos, Philippos
    Trichopoulou, Antonia
    Agnoli, Claudia
    Mattiello, Amalia
    Palli, Domenico
    Tumino, Rosario
    Sacerdote, Carlotta
    van Duijnhoven, Franzel J. B.
    Braaten, Tonje
    Lund, Eiliv
    Skeie, Guri
    Redondo, Maria-Luisa
    Buckland, Genevieve
    Sanchez Perez, Maria Jose
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Amiano, Pilar
    Wirfalt, Elisabet
    Wallstrom, Peter
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E.
    Key, Timothy J.
    Rinaldi, Sabina
    Romieu, Isabelle
    Gallo, Valentina
    Riboli, Elio
    van Gils, Carla H.
    Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study2015In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 17, article id 15Article in journal (Refereed)
    Abstract [en]

    Introduction: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer. Methods: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated. Results: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR = 0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; P-trend = 0.029. While there was no significant effect modification by hormone receptor status (P = 0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P = 0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR = 0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (P-trend = 0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR = 0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer. Conclusions: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.

  • 15. Biskup, Izabela
    et al.
    Kyrø, Cecilie
    Marklund, Matti
    Olsen, Anja
    van Dam, Rob M.
    Tjonneland, Anne
    Overvad, Kim
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Landberg, Rikard
    Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and risk of type 2 diabetes in Scandinavian men and women2016In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 104, no 1, p. 88-96Article in journal (Refereed)
    Abstract [en]

    Background: Studies that use dietary biomarkers to investigate the association between whole-grain intake and the risk of developing type 2 diabetes (T2D) are lacking. Objective: We examined the association between plasma total alkylresorcinols and the alkylresorcinol C17:0-to-C21:0 ratio, biomarkers of whole-grain wheat and rye intake and relative whole grain rye over whole-grain wheat intake, respectively, and the risk of T2D among Scandinavian men and women. Design: A nested case-control study was established within the Northern Sweden Health and Disease Study and the Danish Diet, Cancer and Health cohort. Alkylresorcinol concentrations and the ratios of C17:0 to C21:0 were determined in plasma samples from 931 case-control pairs. ORs for T2D were calculated for plasma total alkylresorcinol concentration or C17:0-to-C21:0 ratio in quartiles with the use of conditional logistic regression that was adjusted for potential confounders. Additional analyses with whole-grain wheat and rye intake estimated from food-frequency questionnaires (FFQs) as exposures were also performed. Results: The plasma total alkylresorcinol concentration was not associated with T2D risk (OR: 1.34; 95% CI: 0.95, 1.88) for the highest compared with the lowest quartiles in multivariable adjusted models. However, the C17:0-to-C21:0 ratio was associated with a lower diabetes risk (OR: 0.54; 95% CI: 0.37, 0.78). Analyses with whole-grain intake estimated from FFQs yielded similar results. Conclusions: Total whole-grain wheat and rye intake, reflected by alkylresorcinols in plasma, was not associated with a lower risk of T2D in a population with high whole-grain intake. In contrast, the proportion of whole-grain rye to whole-grain wheat intake, indicated by the plasma C17:0-to-C21:0 ratio, was inversely associated with T2D. This suggests that whole-grain intake dominated by rye may be favorable for T2D prevention.

  • 16. Biskup, Izabela
    et al.
    Kyrø, Cecilie
    Marklund, Matti
    Olsen, Anja
    van Dam, Rob M.
    Tjønneland, Anne
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Landberg, Rikard
    Reply to A Abbasi2016In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 104, no 6, p. 1725-1726Article in journal (Refereed)
  • 17. Biskup, Izabela
    et al.
    Kyrø, Cecilie
    Marklund, Matti
    Olsen, Anja
    van Dam, Rob M.
    Tjønneland, Anne
    Overvad, Kim
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Landberg, Rikard
    Reply to J-B Qin et al2016In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 104, no 6, p. 1723-1724Article in journal (Refereed)
  • 18. Bjorck, Lena
    et al.
    Rosengren, Annika
    Winkvist, Anna
    Capewell, Simon
    Adiels, Martin
    Bandosz, Piotr
    Critchley, Julia
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Guzman-Castillo, Maria
    O'Flaherty, Martin
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Changes in Dietary Fat Intake and Projections for Coronary Heart Disease Mortality in Sweden: A Simulation Study2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, article id e0160474Article in journal (Refereed)
    Abstract [en]

    Objective In Sweden, previous favourable trends in blood cholesterol levels have recently levelled off or even increased in some age groups since 2003, potentially reflecting changing fashions and attitudes towards dietary saturated fatty acids (SFA). We aimed to examine the potential effect of different SFA intake on future coronary heart disease (CHD) mortality in 2025. Methods We compared the effect on future CHD mortality of two different scenarios for fat intake a) daily SFA intake decreasing to 10 energy percent (E%), and b) daily SFA intake rising to 20 E %. We assumed that there would be moderate improvements in smoking (5%), salt intake (1g/day) and physical inactivity (5% decrease) to continue recent, positive trends. Results In the baseline scenario which assumed that recent mortality declines continue, approximately 5,975 CHD deaths might occur in year 2025. Anticipated improvements in smoking, dietary salt intake and physical activity, would result in some 380 (-6.4%) fewer deaths (235 in men and 145 in women). In combination with a mean SFA daily intake of 10 E%, a total of 810 (-14%) fewer deaths would occur in 2025 (535 in men and 275 in women). If the overall consumption of SFA rose to 20 E%, the expected mortality decline would be wiped out and approximately 20 (0.3%) additional deaths might occur. Conclusion CHD mortality may increase as a result of unfavourable trends in diets rich in saturated fats resulting in increases in blood cholesterol levels. These could cancel out the favourable trends in salt intake, smoking and physical activity.

  • 19.
    Bodén, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ingegerd
    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.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Shivappa, Nitin
    Hebert, James R
    Nilsson, Lena Maria
    Umeå University, Arctic Research Centre at Umeå University. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Dietary inflammatory index and risk of first myocardial infarction: a prospective population-based study2017In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 16, article id 21Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Chronic, low-grade inflammation is an established risk factor for cardiovascular disease. The inflammatory impact of diet can be reflected by concentrations of inflammatory markers in the bloodstream and the inflammatory potential of diet can be estimated by the dietary inflammatory index (DII(TM)), which has been associated with cardiovascular disease risk in some previous studies. We aimed to examine the association between the DII and the risk of first myocardial infarction (MI) in a population-based study with long follow-up.

    METHOD: We conducted a prospective case-control study of 1389 verified cases of first MI and 5555 matched controls nested within the population-based cohorts of the Northern Sweden Health and Disease Study (NSHDS), of which the largest is the ongoing Västerbotten Intervention Programme (VIP) with nearly 100 000 participants during the study period. Median follow-up from recruitment to MI diagnosis was 6.4 years (6.2 for men and 7.2 for women). DII scores were derived from a validated food frequency questionnaire (FFQ) administered in 1986-2006. Multivariable conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using quartile 1 (most anti-inflammatory diet) as the reference category. For validation, general linear models were used to estimate the association between the DII scores and two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) in a subset (n = 605) of the study population.

    RESULTS: Male participants with the most pro-inflammatory DII scores had an increased risk of MI [ORQ4vsQ1 = 1.57 (95% CI 1.21-2.02) P trend = 0.02], which was essentially unchanged after adjustment for potential confounders, including cardiovascular risk factors [ORQ4vsQ1 = 1.50 (95% CI 1.14-1.99), P trend = 0.10]. No association was found between DII and MI in women. An increase of one DII score unit was associated with 9% higher hsCRP (95% CI 0.03-0.14) and 6% higher IL-6 (95% CI 0.02-0.11) in 605 controls with biomarker data available.

    CONCLUSION: A pro-inflammatory diet was associated with an elevated risk of first myocardial infarction in men; whereas for women the relationship was null. Consideration of the inflammatory impact of diet could improve prevention of cardiovascular disease.

  • 20. Boeing, H
    et al.
    Dietrich, T
    Hoffmann, K
    Pischon, T
    Ferrari, P
    Lahmann, PH
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Allen, N
    Key, T
    Skeie, G
    Lund, E
    Olsen, A
    Tjonneland, A
    Overvad, K
    Jensen, MK
    Rohrmann, S
    Linseisen, J
    Trichopoulou, A
    Bamia, C
    Psalttopoulou, T
    Weinehall, L
    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, Cariology.
    Sanchez, MJ
    Jakszyn, P
    Ardanaz, E
    Amiano, P
    Chirlaque, MD
    Quiros, JR
    Wirfalt, E
    Berglund, G
    Peeters, PH
    van Gils, CH
    Bueno-de-Mesquita, HB
    Buchner, FL
    Berrino, F
    Palli, D
    Sacerdote, C
    Tumino, R
    Panico, S
    Bingham, S
    Khaw, KT
    Slimani, N
    Norat, T
    Jenab, M
    Riboli, E
    Intake of fruits and vegetables and risk of cancer of the upper aero-digestive tract: the prospective EPIC-study.2006In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 17, no 7, p. 957-969Article in journal (Refereed)
    Abstract [en]

    Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (<120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.

  • 21. Boffetta, Paolo
    et al.
    Couto, Elisabeth
    Wichmann, Janine
    Ferrari, Pietro
    Trichopoulos, Dimitrios
    Bueno-de-Mesquita, H Bas
    van Duijnhoven, Fränzel J B
    Büchner, Frederike L
    Key, Tim
    Boeing, Heiner
    Nöthlings, Ute
    Linseisen, Jakob
    Gonzalez, Carlos A
    Overvad, Kim
    Nielsen, Michael R S
    Tjønneland, Anne
    Olsen, Anja
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Lagiou, Pagona
    Naska, Androniki
    Benetou, Vassiliki
    Kaaks, Rudolf
    Rohrmann, Sabine
    Panico, Salvatore
    Sieri, Sabina
    Vineis, Paolo
    Palli, Domenico
    van Gils, Carla H
    Peeters, Petra H
    Lund, Eiliv
    Brustad, Magritt
    Engeset, Dagrun
    Huerta, José María
    Rodríguez, Laudina
    Sánchez, Maria-José
    Dorronsoro, Miren
    Barricarte, Aurelio
    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 Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Manjer, Jonas
    Sonestedt, Emily
    Allen, Naomi E
    Bingham, Sheila
    Khaw, Kay-Tee
    Slimani, Nadia
    Jenab, Mazda
    Mouw, Traci
    Norat, Teresa
    Riboli, Elio
    Trichopoulou, Antonia
    Fruit and vegetable intake and overall cancer risk in the European prospective investigation into cancer and nutrition (EPIC)2010In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 102, no 8, p. 529-537Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk. METHODS: We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking. RESULTS: Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol. CONCLUSIONS: A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation.

  • 22. Boström, Elisabeth A.
    et al.
    Kindstedt, Elin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sulniute, Rima
    Umeå University, Faculty of Medicine, Department of Odontology.
    Palmqvist, Py
    Umeå University, Faculty of Medicine, Department of Odontology.
    Majster, Mirjam
    Holm, Cecilia Koskinen
    Umeå University, Faculty of Medicine, Department of Odontology.
    Zwicker, Stephanie
    Clark, Reuben
    Önell, Sebastian
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lerner, Ulf H.
    Umeå University, Faculty of Medicine, Department of Odontology. Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Gothenburg, Sweden.
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, article id e0134608Article in journal (Refereed)
    Abstract [en]

    Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-alpha (TNF-alpha and interleukin-1 beta (IL-1 beta), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-kappa B pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in periodontitis and maybe prevent tooth loss.

  • 23. Bratt, P
    et al.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Linder, J
    Ericson, T
    Function of the rat salivary glands after exposure to inorganic mercury1995In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 172, no 1, p. 47-55Article in journal (Refereed)
    Abstract [en]

    In spite of many studies on the toxicity of mercury, very little is known about the effects of mercury on the function of exocrine glands. In the present paper selected functions of Sprague-Dawley rat salivary glands were studied after the exposure of the animals to inorganic mercury at two different doses; 3.25 mg/kg body weight given during 25 days and 7.0 mg/kg body weight given during 27 days. The function of the salivary glands was estimated by saliva secretion rate, secretion of electrolytes, proteins and biosynthesis of glycoproteins. The function was compared between mercury exposed rats and age and sex matched control rats that were given injections with equal volumes of 0.154 mol/l NaCl on the same time schedule. In the present study we report that no significant effect on saliva secretion rate, concentrations of salivary constituents or biosynthesis of glycoproteins in the salivary glands could be observed in rats as a result of mercury exposure at two levels that gave 30 or 60 times higher serum mercury concentrations than in the majority of the Swedish population.

  • 24. Brunkwall, Louise
    et al.
    Chen, Yan
    Hindy, George
    Rukh, Gull
    Ericson, Ulrika
    Barroso, Ines
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    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, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA.
    Orho-Melander, Marju
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts2016In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 104, no 3, p. 809-815Article in journal (Refereed)
    Abstract [en]

    Background: The consumption of sugar-sweetened beverages (SSBs), which has increased substantially during the last decades, has been associated with obesity and weight gain.

    Objective: Common genetic susceptibility to obesity has been shown to modify the association between SSB intake and obesity risk in 3 prospective cohorts from the United States. We aimed to replicate these findings in 2 large Swedish cohorts.

    Design: Data were available for 21,824 healthy participants from the Malmö Diet and Cancer study and 4902 healthy participants from the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk Study. Self-reported SSB intake was categorized into 4 levels (seldom, low, medium, and high). Unweighted and weighted genetic risk scores (GRSs) were constructed based on 30 body mass index [(BMI) in kg/m2]-associated loci, and effect modification was assessed in linear regression equations by modeling the product and marginal effects of the GRS and SSB intake adjusted for age-, sex-, and cohort-specific covariates, with BMI as the outcome. In a secondary analysis, models were additionally adjusted for putative confounders (total energy intake, alcohol consumption, smoking status, and physical activity).

    Results: In an inverse variance-weighted fixed-effects meta-analysis, each SSB intake category increment was associated with a 0.18 higher BMI (SE = 0.02; P = 1.7 × 10−20n = 26,726). In the fully adjusted model, a nominal significant interaction between SSB intake category and the unweighted GRS was observed (P-interaction = 0.03). Comparing the participants within the top and bottom quartiles of the GRS to each increment in SSB intake was associated with 0.24 (SE = 0.04; P = 2.9 × 10−8n = 6766) and 0.15 (SE = 0.04; P = 1.3 × 10−4n = 6835) higher BMIs, respectively.

    Conclusions: The interaction observed in the Swedish cohorts is similar in magnitude to the previous analysis in US cohorts and indicates that the relation of SSB intake and BMI is stronger in people genetically predisposed to obesity.

  • 25. Buckland, G
    et al.
    Travier, N
    Cottet, V
    Gonzalez, CA
    Lujan-Barroso, L
    Agudo, A
    Trichopoulou, A
    Lagiou, P
    Trichopoulos, D
    Peeters, PH
    May, A
    Bueno-de-Mesquita, HB
    Duijnhoven, FJ Bvan
    Key, TJ
    Allen, N
    Khaw, KT
    Wareham, N
    Romieu, I
    McCormack, V
    Boutron-Ruault, M
    Clavel-Chapelon, F
    Panico, S
    Agnoli, C
    Palli, D
    Tumino, R
    Vineis, P
    Amiano, P
    Barricarte, A
    Rodriguez, L
    Sanchez, MJ
    Chirlaque, MD
    Kaaks, R
    Teucher, B
    Boeing, H
    Bergmann, MM
    Overvad, K
    Dahm, CC
    Tjonneland, A
    Olsen, A
    Manjer, J
    Wirfalt, E
    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, School of Dentistry.
    Lund, E
    Hjartaker, A
    Skeie, G
    Vergnaud, AC
    Norat, T
    Romaguera, D
    Riboli, E
    Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, no 12, p. 2918-2927Article in journal (Refereed)
    Abstract [en]

    Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER/PR]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER/PR tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification.

  • 26. Buckland, Genevieve
    et al.
    Agudo, Antonio
    Luján, Leila
    Jakszyn, Paula
    Bueno-de-Mesquita, H Bas
    Palli, Domenico
    Boeing, Heiner
    Carneiro, Fátima
    Krogh, Vittorio
    Sacerdote, Carlotta
    Tumino, Rosario
    Panico, Salvatore
    Nesi, Gabriella
    Manjer, Jonas
    Regnér, Sara
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sanchez, María-José
    Dorronsoro, Miren
    Barricarte, Aurelio
    Navarro, Carmen
    Quirós, J Ramón
    Allen, Naomi E
    Key, Timothy J
    Bingham, Sheila
    Kaaks, Rudolf
    Overvad, Kim
    Jensen, Majken
    Olsen, Anja
    Tjønneland, Anne
    Peeters, Petra H M
    Numans, Mattijs E
    Ocké, Marga C
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Boutron-Ruault, Marie-Christine
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Lund, Eiliv
    Couto, Elisabeth
    Boffeta, Paolo
    Jenab, Mazda
    Riboli, Elio
    Romaguera, Dora
    Mouw, Traci
    González, Carlos A
    Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study2010In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 91, no 2, p. 381-390Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Mediterranean dietary pattern is believed to protect against cancer, although evidence from cohort studies that have examined particular cancer sites is limited.

    OBJECTIVE: We aimed to explore the association between adherence to a relative Mediterranean diet (rMED) and incident gastric adenocarcinoma (GC) within the European Prospective Investigation into Cancer and Nutrition study.

    DESIGN: The study included 485,044 subjects (144,577 men) aged 35-70 y from 10 European countries. At recruitment, dietary and lifestyle information was collected. An 18-unit rMED score, incorporating 9 key components of the Mediterranean diet, was used to estimate rMED adherence. The association between rMED and GC with respect to anatomic location (cardia and noncardia) and histologic types (diffuse and intestinal) was investigated. A calibration study in a subsample was used to control for dietary measurement error.

    RESULTS: After a mean follow-up of 8.9 y, 449 validated incident GC cases were identified and used in the analysis. After stratification by center and age and adjustment for recognized cancer risk factors, high compared with low rMED adherence was associated with a significant reduction in GC risk (hazard ratio: 0.67; 95% CI: 0.47, 0.94). A 1-unit increase in the rMED score was associated with a decreased risk of GC of 5% (95% CI: 0.91, 0.99). There was no evidence of heterogeneity between different anatomic locations or histologic types. The calibrated results showed similar trends (overall hazard ratio for GC: 0.93; 95% CI: 0.89, 0.99).

    CONCLUSION: Greater adherence to an rMED is associated with a significant reduction in the risk of incident GC.

  • 27. Bäckström, I
    et al.
    Funegård, Ulrika
    Andersson, I
    Franzén, L
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Dietary intake in head and neck irradiated patients with permanent dry mouth symptoms.1995In: European Journal of Cancer. Part B, Oral Oncology, ISSN 0964-1955, Vol. 31B, no 4, p. 253-257Article in journal (Refereed)
    Abstract [en]

    Radiotherapy of the head and neck region, which includes the major and minor salivary glands in the radiation field, usually leads to temporary or permanent xerostomia. This may affect eating and increase the risk of inadequate intake of energy and nutrients. The aim of the present study was to investigate the effects of radiotherapy-induced xerostomia on energy and nutrient intake in individuals treated for malignancies in the head and neck region. The dietary intake of 24 patients with a low chewing stimulated whole saliva flow rate (< 0.5 ml/min) and in age and sex matched controls with normal flow rate (> 1.0 ml/min) was recorded for 7 days. The average daily energy intake was nearly 300 kcal lower in the irradiated patients with dry mouth symptoms than in the control group. The mean intake in the former group was 1925 kcal per day whereas the control group had an intake of 2219 kcal per day. Irradiated patients with dry mouth symptoms had significantly lower mean intakes of vitamin A, beta-carotene, vitamin E, vitamin B6, folacine, iron and zinc than those in the control group. There was also a lower intake of vitamin C, but this was not statistically significant. The intake of vitamins A and C exceeded or reached the levels recommended in the Swedish Nutritional recommendations, but the average intakes of fibre, iron, beta-carotene, vitamin E, zinc, selenium, and iron did not reach recommended levels, in neither the experimental nor the control group. There was a slight positive correlation between energy intake and saliva secretion rate in the control group, but the energy intake was totally independent of variations in secretion rate in the irradiated patients with low secretion rate.

  • 28. Campmans-Kuijpers, Marjo J. E.
    et al.
    Sluijs, Ivonne
    Noethlings, Ute
    Freisling, Heinz
    Overvad, Kim
    Weiderpass, Elisabete
    Fagherazzi, Guy
    Kuehn, Tilman
    Katzke, Verena A.
    Mattiello, Amalia
    Sonestedt, Emily
    Masala, Giovanna
    Agnoli, Claudia
    Tumino, Rosario
    Spijkerman, Annemieke M. W.
    Barricarte, Aurelio
    Ricceri, Fulvio
    Chamosa, Saioa
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Winkvist, Anna
    Tjonneland, Anne
    Sluik, Diewertje
    Boeing, Heiner
    Beulens, Joline W. J.
    Isocaloric substitution of carbohydrates with protein: the association with weight change and mortality among patients with type 2 diabetes2015In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 14, article id 39Article in journal (Refereed)
    Abstract [en]

    Background: The health impact of dietary replacement of carbohydrates with protein for patients with type 2 diabetes is still debated. This study aimed to investigate the association between dietary substitution of carbohydrates with (animal and plant) protein and 5-year weight change, and all-cause and cardiovascular (CVD) mortality risk in patients with type 2 diabetes.

    Methods: The study included 6,107 diabetes patients from 15 European cohorts. Patients with type 1 diabetes were excluded. At recruitment, validated country-specific food-frequency questionnaires were used to estimate dietary intake. Multivariable adjusted linear regression was used to examine the associations between dietary carbohydrate substitution with protein and 5-year weight change, and Cox regression to estimate hazard ratios (HRs) for (CVD) mortality.

    Results: Annual weight loss of patients with type 2 diabetes was 0.17 (SD 1.24) kg. After a mean follow-up of 9.2 (SD 2.3)y, 787 (13%) participants had died, of which 266 (4%) deaths were due to CVD. Substitution of 10 gram dietary carbohydrate with total (ß = 187 [75;299]g) and animal (ß = 196 [137;254]g) protein was associated with mean 5-year weight gain. Substitution for plant protein was not significantly associated with weight change (β = 82 [−421;584]g). Substitution with plant protein was associated with lower all-cause mortality risk (HR = 0.79 [0.64;0.97]), whereas substitution with total or animal protein was not associated with (CVD) mortality risk.

    Conclusions: In diabetes patients, substitution with plant protein was beneficial with respect to weight change and all-cause mortality as opposed to substitution with animal protein. Therefore, future research is needed whether dietary guidelines should not actively promote substitution of carbohydrates by total protein, but rather focus on substitution of carbohydrates with plant protein.

  • 29. Campmans-Kuijpers, Marjo J
    et al.
    Sluijs, Ivonne
    Nöthlings, Ute
    Freisling, Heinz
    Overvad, Kim
    Boeing, Heiner
    Masala, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Sieri, Sabina
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Winkvist, Anna
    Katzke, Verena A
    Kuehn, Tilman
    Nilsson, Peter M
    Halkjær, Jytte
    Tjønneland, Anne
    Spijkerman, Annemieke M
    Arriola, Larraitz
    Sacerdote, Carlotta
    Barricarte, Aurelio
    May, Anne M
    Beulens, Joline W
    The association of substituting carbohydrates with total fat and different types of fatty acids with mortality and weight change among diabetes patients2016In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 35, no 5, p. 1096-1102Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Substitution of carbohydrates with fat in a diet for type 2 diabetes patients is still debated.

    OBJECTIVE: This study aimed to investigate the association between dietary carbohydrate intake and isocaloric substitution with (i) total fat, (ii) saturated fatty acids (SFA), (iii) mono-unsaturated fatty acids (MUFA) and (iv) poly-unsaturated fatty acids (PUFA) with all-cause and cardiovascular (CVD) mortality risk and 5-year weight change in patients with type 2 diabetes.

    METHODS: The study included 6192 patients with type 2 diabetes from 15 cohorts of the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at recruitment with country-specific food-frequency questionnaires. Cox and linear regression were used to estimate the associations with (CVD) mortality and weight change, adjusting for confounders and using different methods to adjust for energy intake.

    RESULTS: After a mean follow-up of 9.2 y ± SD 2.3 y, 791 (13%) participants had died, of which 268 (4%) due to CVD. Substituting 10 g or 5 energy% of carbohydrates by total fat was associated with a higher all-cause mortality risk (HR 1.07 [1.02-1.13]), or SFAs (HR 1.25 [1.11-1.40]) and a lower risk when replaced by MUFAs (HR 0.89 [0.77-1.02]). When carbohydrates were substituted with SFAs (HR 1.22 [1.00-1.49]) or PUFAs (HR 1.29 [1.02-1.63]) CVD mortality risk increased. The 5-year weight was lower when carbohydrates were substituted with total fat or MUFAs. These results were consistent over different energy adjustment methods.

    CONCLUSIONS: In diabetes patients, substitution of carbohydrates with SFAs was associated with a higher (CVD) mortality risk and substitution by total fat was associated with a higher all-cause mortality risk. Substitution of carbohydrates with MUFAs may be associated with lower mortality risk and weight reduction. Instead of promoting replacement of carbohydrates by total fat, dietary guideline should continue focusing on replacement by fat-subtypes; especially SFAs by MUFAs.

  • 30. Cederholm, Tommy
    et al.
    Marcus, Claude
    Rössner, Stephan
    Hellénius, Mai-Lis
    Björck, Inger
    Bosaeus, Ingvar
    Forsum, Elisabet
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hulthén, Lena
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Odontology.
    Larsson, Jörgen
    Lissner, Lauren
    Nilsson, Ake
    Nyman, Margareta
    Palmblad, Jan
    Sandberg, Ann-Sofie
    Aman, Per
    Replik till Lars-Erik Holm: Forskaren, samhället och jäv [The researcher, the society and partiality]2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 16, p. 1206-1207Article in journal (Refereed)
  • 31. Chajes, Veronique
    et al.
    Biessy, Carine
    Ferrari, Pietro
    Romieu, Isabelle
    Freisling, Heinz
    Huybrechts, Inge
    Scalbert, Augustin
    de Mesquita, Bas Bueno
    Romaguera, Dora
    Gunter, Marc J.
    Vineis, Paolo
    Hansen, Camilla Plambeck
    Jakobsen, Marianne Uhre
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Boutron-Ruault, Marie-Christine
    Katzke, Verana
    Neamat-Allah, Jasmine
    Boeing, Heiner
    Bachlechner, Ursula
    Trichopoulou, Antonia
    Naska, Androniki
    Orfanos, Philippos
    Pala, Valeria
    Masala, Giovanna
    Mattiello, Amalia
    Skeie, Guri
    Weiderpass, Elisabete
    Agudo, Antonio
    Maria Huerta, Jose
    Ardanaz, Eva
    Jose Sanchez, Maria
    Dorronsoro, Miren
    Ramon Quiros, Jose
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Winkvist, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sonested, Emily
    Key, Tim
    Khaw, Kay-Tee
    Wareham, Nicolas J.
    Peeters, Petra H. M.
    Slimani, Nadia
    Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 2, article id e0118206Article in journal (Refereed)
    Abstract [en]

    Background Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition ( EPIC) cohort. Methods Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow- up, age, energy, alcohol, smoking status, physical activity, and region. Results In women, doubling elaidic acid was associated with a decreased risk of weight loss ( odds ratio ( OR) = 0.69, 95% confidence interval ( CI) = 0.55- 0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5- year follow- up ( OR = 1.23, 95% CI = 0.97- 1.56, p = 0.082) ( p- trend<. 0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss ( OR = 0.82, 95% CI = 0.66- 1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5- year follow- up ( OR = 1.08, 95% CI = 0.88- 1.33, p = 0.454). No association was found for saturated and cismonounsaturated fatty acids. Conclusions These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially- produced trans fatty acids.

  • 32. Chajès, Véronique
    et al.
    Biessy, Carine
    Byrnes, Graham
    Deharveng, Geneviève
    Saadatian-Elahi, Mitra
    Jenab, Mazda
    Peeters, Petra H M
    Ocké, Marga
    Bueno-de-Mesquita, H Bas
    Johansson, Ingegerd
    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.
    Manjer, Jonas
    Wirfält, Elisabet
    Jakszyn, Paula
    González, Carlos A
    Huerta, Jose-Maria
    Martinez, Carmen
    Amiano, Pilar
    Suárez, Laudina Rodriguez
    Ardanaz, Eva
    Tjønneland, Anne
    Halkjaer, Jytte
    Overvad, Kim
    Jakobsen, Marianne Uhre
    Berrino, Franco
    Pala, Valeria
    Palli, Domenico
    Tumino, Rosario
    Vineis, Paolo
    de Magistris, Maria Santucci
    Spencer, Elisabeth A
    Crowe, Francesca L
    Bingham, Sheila
    Khaw, Kay-Tee
    Linseisen, Jakob
    Rohrmann, Sabine
    Boeing, Heiner
    Nöethlings, Ute
    Olsen, Karina Standahl
    Skeie, Guri
    Lund, Eiliv
    Trichopoulou, Antonia
    Zilis, Dimosthenis
    Oustoglou, Erifili
    Clavel-Chapelon, Françoise
    Riboli, Elio
    Slimani, Nadia
    Ecological-level associations between highly processed food intakes and plasma phospholipid elaidic acid concentrations: results from a cross-sectional study within the European prospective investigation into cancer and nutrition (EPIC).2011In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 63, no 8, p. 1235-50Article in journal (Refereed)
    Abstract [en]

    Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.

  • 33. Chuang, Shu-Chun
    et al.
    Norat, Teresa
    Murphy, Neil
    Olsen, Anja
    Tjonneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie Christine
    Perquier, Florence
    Dartois, Laureen
    Kaaks, Rudolf
    Teucher, Birgit
    Bergmann, Manuela M.
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Grioni, Sara
    Sacerdote, Carlotta
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Peeters, Petra H. M.
    Bueno-de-Mesquita, Bas
    Ros, Martine M.
    Brustad, Magritt
    Asli, Lene Angell
    Skeie, Guri
    Quiros, J. Ramon
    Gonzalez, Carlos A.
    Sanchez, Maria-Jose
    Navarro, Carmen
    Aicua, Eva Ardanaz
    Dorronsoro, Miren
    Drake, Isabel
    Sonestedt, Emily
    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, Nutritional Research.
    Key, Timothy
    Crowe, Francesca
    Khaw, Kay-Tee
    Wareham, Nicholas
    Ferrari, Pietro
    Slimani, Nadia
    Romieu, Isabelle
    Gallo, Valentina
    Riboli, Elio
    Vineis, Paolo
    Fiber intake and total and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition cohort2012In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 96, no 1, p. 164-174Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have shown that high fiber intake is associated with lower mortality. However, little is known about the association of dietary fiber with specific causes of death other than cardiovascular disease (CVD). Objective: The aim of this study was to assess the relation between fiber intake, mortality, and cause-specific mortality in a large European prospective study of 452,7 I 7 men and women. Design: HRs and 95% CIs were estimated by using Cox proportional hazards models, stratified by age, sex, and center and adjusted for education, smoking, alcohol consumption, BMI, physical activity, total energy intake, and, in women, ever use of menopausal hormone therapy. Results: During a mean follow-up of 12.7 y, a total of 23,582 deaths were recorded. Fiber intake was inversely associated with total mortality (HRper (10-g/d) (increase): 0.90; 95% Cl: 0.88, 0.92); with mortality from circulatory (HRper (10-g/d increase): 0.90 and 0.88 for men and women, respectively), digestive (HR: 0.61 and 0.64), respiratory (HR: 0.77 and 0.62), and non-CVD noncancer inflammatory (HR: 0.85 and 0.80) diseases; and with smoking-related cancers (HR: 0.86 and 0.89) but not with non-smoking-related cancers (HR: 1.05 and 0.97). The associations were more evident for fiber from cereals and vegetables than from fruit. The associations were similar across BMI and physical activity categories but were stronger in smokers and participants who consumed >18 g alcohol/d. Conclusions: Higher fiber intake is associated with lower mortality, particularly from circulatory, digestive, and non-CVD noncancer inflammatory diseases. Our results support current recommendations of high dietary fiber intake for health maintenance. Am J Clin Nutr 2012;96:164-74.

  • 34. Cornelis, M C
    et al.
    Byrne, E M
    Esko, T
    Nalls, M A
    Ganna, A
    Paynter, N
    Monda, K L
    Amin, N
    Fischer, K
    Renstrom, F
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Ngwa, J S
    Huikari, V
    Cavadino, A
    Nolte, I M
    Teumer, A
    Yu, K
    Marques-Vidal, P
    Rawal, R
    Manichaikul, A
    Wojczynski, M K
    Vink, J M
    Zhao, J H
    Burlutsky, G
    Lahti, J
    Mikkilä, V
    Lemaitre, R N
    Eriksson, J
    Musani, S K
    Tanaka, T
    Geller, F
    Luan, J
    Hui, J
    Mägi, R
    Dimitriou, M
    Garcia, M E
    Ho, W-K
    Wright, M J
    Rose, L M
    Magnusson, P K E
    Pedersen, N L
    Couper, D
    Oostra, B A
    Hofman, A
    Ikram, M A
    Tiemeier, H W
    Uitterlinden, A G
    van Rooij, F J A
    Barroso, I
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Xue, L
    Kaakinen, M
    Milani, L
    Power, C
    Snieder, H
    Stolk, R P
    Baumeister, S E
    Biffar, R
    Gu, F
    Bastardot, F
    Kutalik, Z
    Jacobs, D R
    Forouhi, N G
    Mihailov, E
    Lind, L
    Lindgren, C
    Michaëlsson, K
    Morris, A
    Jensen, M
    Khaw, K-T
    Luben, R N
    Wang, J J
    Männistö, S
    Perälä, M-M
    Kähönen, M
    Lehtimäki, T
    Viikari, J
    Mozaffarian, D
    Mukamal, K
    Psaty, B M
    Döring, A
    Heath, A C
    Montgomery, G W
    Dahmen, N
    Carithers, T
    Tucker, K L
    Ferrucci, L
    Boyd, H A
    Melbye, M
    Treur, J L
    Mellström, D
    Hottenga, J J
    Prokopenko, I
    Tönjes, A
    Deloukas, P
    Kanoni, S
    Lorentzon, M
    Houston, D K
    Liu, Y
    Danesh, J
    Rasheed, A
    Mason, M A
    Zonderman, A B
    Franke, L
    Kristal, B S
    Karjalainen, J
    Reed, D R
    Westra, H-J
    Evans, M K
    Saleheen, D
    Harris, T B
    Dedoussis, G
    Curhan, G
    Stumvoll, M
    Beilby, J
    Pasquale, L R
    Feenstra, B
    Bandinelli, S
    Ordovas, J M
    Chan, A T
    Peters, U
    Ohlsson, C
    Gieger, C
    Martin, N G
    Waldenberger, M
    Siscovick, D S
    Raitakari, O
    Eriksson, J G
    Mitchell, P
    Hunter, D J
    Kraft, P
    Rimm, E B
    Boomsma, D I
    Borecki, I B
    Loos, R J F
    Wareham, N J
    Vollenweider, P
    Caporaso, N
    Grabe, H J
    Neuhouser, M L
    Wolffenbuttel, B H R
    Hu, F B
    Hyppönen, E
    Järvelin, M-R
    Cupples, L A
    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; Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Ridker, P M
    van Duijn, C M
    Heiss, G
    Metspalu, A
    North, K E
    Ingelsson, E
    Nettleton, J A
    van Dam, R M
    Chasman, D I
    Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption2015In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, no 5, p. 647-656Article in journal (Refereed)
    Abstract [en]

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

  • 35. Couto, E
    et al.
    Boffetta, P
    Lagiou, P
    Ferrari, P
    Buckland, G
    Overvad, K
    Dahm, C C
    Tjønneland, A
    Olsen, A
    Clavel-Chapelon, F
    Boutron-Ruault, M-C
    Cottet, V
    Trichopoulos, D
    Naska, A
    Benetou, V
    Kaaks, R
    Rohrmann, S
    Boeing, H
    von Ruesten, A
    Panico, S
    Pala, V
    Vineis, P
    Palli, D
    Tumino, R
    May, A
    Peeters, P H
    Bueno-de-Mesquita, H B
    Büchner, F L
    Lund, E
    Skeie, G
    Engeset, D
    Gonzalez, C A
    Navarro, C
    Rodríguez, L
    Sánchez, M-J
    Amiano, P
    Barricarte, A
    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.
    Manjer, J
    Wirfärt, E
    Allen, N E
    Crowe, F
    Khaw, K-T
    Wareham, N
    Moskal, A
    Slimani, N
    Jenab, M
    Romaguera, D
    Mouw, T
    Norat, T
    Riboli, E
    Trichopoulou, A
    Mediterranean dietary pattern and cancer risk in the EPIC cohort.2011In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, no 9, p. 1493-1499Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse.

    METHODS: We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142,605 men and 335,873. Adherence to Mediterranean diet was examined using a score (range: 0-9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders.

    RESULTS: In all, 9669 incident cancers in men and 21,062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95-0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern.

    CONCLUSION: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.

  • 36. Cust, A E
    et al.
    Skilton, M R
    van Bakel, M M E
    Halkjaer, J
    Olsen, A
    Agnoli, C
    Psaltopoulou, T
    Buurma, E
    Sonestedt, E
    Chirlaque, M D
    Rinaldi, S
    Tjønneland, A
    Jensen, M K
    Clavel-Chapelon, F
    Boutron-Ruault, M C
    Kaaks, R
    Nöthlings, U
    Chloptsios, Y
    Zylis, D
    Mattiello, A
    Caini, S
    Ocké, M C
    van der Schouw, Y T
    Skeie, G
    Parr, C L
    Molina-Montes, E
    Manjer, J
    Johansson, I
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    McTaggart, A
    Key, T J
    Bingham, S
    Riboli, E
    Slimani, N
    Total dietary carbohydrate, sugar, starch and fibre intakes in the European Prospective Investigation into Cancer and Nutrition.2009In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 63 Suppl 4, p. S37-60Article in journal (Refereed)
    Abstract [en]

    Dietary carbohydrate intakes and in particular their food sources varied considerably between these 10 European countries. Intakes also varied according to gender and lifestyle factors. These data will form the basis for future aetiological analyses of the role of dietary carbohydrates in influencing health and disease.

  • 37.
    Dahlin, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    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, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 32, no 2, p. 304-314Article in journal (Refereed)
    Abstract [en]

    In this nested case-referent study, we related plasma concentrations of vitamin B12 to the risk of colorectal cancer, taking into consideration prediagnostic plasma folate and total homocysteine concentrations. Subjects were 226 cases and double matched referents from the population-based Northern Sweden Health and Disease Study. Follow-up times from recruitment to diagnosis ranged from 0.1 to 12.7 years, with a median of 4.2 years. Plasma vitamin B12 concentrations were inversely associated with the risk of rectal cancer: univariate odds ratio for the highest versus lowest quintile 0.34 (95% confidence interval (95% CI) 0.13-0.83), p(trend) = 0.004. Risk estimates were attenuated slightly but remained statistically significant after adjustment for body mass index, current smoking, recreational and occupational physical activity, alcohol intake and prediagnostic plasma folate and total homocysteine concentrations: OR 0.30 (95% CI 0.08-0.99), p(trend) = 0.025. The corresponding univariate and fully adjusted odds ratios for colon cancer were 1.25 (CI 0.66-2.36), p(trend) = 0.185 and 1.42 (CI 0.67-3.05), p(trend) = 0.113, respectively. The observed over-risk was attributable to left-sided colon cancer. Interaction analyses including vitamin B12, folate and homocysteine were in line with the results for vitamin B12 alone. In conclusion, these results suggest that increasing levels of plasma vitamin B12, alone or together with other factors involved in one-carbon metabolism, may reduce the risk of rectal cancer, whereas for colon cancer, the association appears to be less clear.

  • 38.
    Danielsson Niemi, Liza
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Human milk compounds inhibiting adhesion of mutans streptococci to host ligand-coated hydroxyapatite in vitro2009In: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 43, no 3, p. 171-178Article in journal (Refereed)
    Abstract [en]

    Acquisition of mutans streptococci at an early age is a risk factor for later caries development. Following our recent finding that human milk may inhibit adhesion of Streptococcus mutans the aim of the present study was to identify compounds in human milk preventing adhesion of mutans streptococci to saliva- or gp340-coated hydroxyapatite (s-HA and gp340-HA) using an in vitro model system. Superdex 200 fractions of human milk and purified proteins were screened for binding inhibition of the S. mutans strain Ingbritt. Avid inhibition was seen to both s-HA and gp340-HA for caseins, lactoferrin, IgA and IgG, and moderate inhibition for alpha-lactalbumin and bile salt-stimulated lipase, whereas albumin and lysozyme had no effect. The inhibitory epitope in beta-casein was delineated to its C-terminal LLNQELLNPTHQIYPVTQPLAPVHNPISV stretch by use of synthetic peptides. Similarly, a peptide (SCKFDEYFSQSCA) corresponding to the human lactoferrin stretch that is highly homologous to the previously shown inhibitory stretch of bovine lactoferrin was found to inhibit S. mutans Ingbritt binding. Inhibition by human milk, IgA, and the inhibitory beta-casein peptide was universal among 4 strains of S. mutans (Ingbritt, NG8, LT11, JBP) and 2 strains of S. sobrinus (6715 and OMZ176). IgG inhibited 4, alpha-lactalbumin 3 and lactoferrin 2 of these 6 strains. It was also confirmed that none of the milk components coated on HA mediated S. mutans Ingbritt adhesion, which was consistent with the finding that no milk protein was recognized on Western blots by gp340/DMBT1 monoclonal antibodies.

  • 39.
    Danielsson Niemi, Liza
    et al.
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Salivary statherin peptide-binding epitopes of commensal and potentially infectious Actinomyces spp. delineated by a hybrid peptide construct2004In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 72, no 2, p. 782-787Article, review/survey (Refereed)
    Abstract [en]

    Adhesion of microorganisms to host receptor molecules such as salivary statherin molecules is a common event in oral microbial colonization. Here we used a hybrid peptide construct (with both a hydroxyapatite-binding portion and a test peptide portion) to map the interaction of Actinomyces species (and Candida albicans) with statherin. Adhesion to hybrid peptides and truncated statherin variants revealed three binding types, types I to III. (i) Type I strains of rat, hamster, and human infection origins bound C-terminal-derived QQYTF and PYQPQY peptides. The QQYTF peptide inhibited statherin binding for some strains but not for others. (ii) Type II strains of human and monkey tooth origins bound middle-region-derived YQPVPE and QPLYPQ peptides. Neither strain was inhibited by soluble peptides. (iii) Type III strains of human infection origins (and C. albicans) did not bind to either statherin-derived peptides or truncated statherin. Moreover, the type I strains inhibited by QQYTF were also inhibited by TF and QAATF peptides and were detached from statherin by the same peptides. In conclusion, it is suggested that commensal and potentially infectious microorganisms bind middle or C-terminal statherin differently and that other microbes might require discontinuous epitopes.

  • 40. Del Gobbo, Liana C.
    et al.
    Imamura, Fumiaki
    Aslibekyan, Stella
    Marklund, Matti
    Virtanen, Jyrki K.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Yakoob, Mohammad Y.
    Chiuve, Stephanie E.
    dela Cruz, Luicito
    Frazier-Wood, Alexis C.
    Fretts, Amanda M.
    Guallar, Eliseo
    Matsumoto, Chisa
    Prem, Kiesha
    Tanaka, Tosh
    Wu, Jason H. Y.
    Zhou, Xia
    Helmer, Catherine
    Ingelsson, Erik
    Yuan, Jian-Min
    Barberger-Gateau, Pascale
    Campos, Hannia
    Chaves, Paulo H. M.
    Djousse, Luc
    Giles, Graham G.
    Gomez-Aracena, Jose
    Hodge, Allison M.
    Hu, Frank B.
    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.
    Khaw, Kay-Tee
    Koh, Woon-Puay
    Lemaitre, Rozenn N.
    Lind, Lars
    Luben, Robert N.
    Rimm, Eric B.
    Riserus, Ulf
    Samieri, Cecilia
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Siscovick, David S.
    Stampfer, Meir
    Steffen, Lyn M.
    Steffen, Brian T.
    Tsai, Michael Y.
    van Dam, Rob M.
    Voutilainen, Sari
    Willett, Walter C.
    Woodward, Mark
    Mozaffarian, Dariush
    omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease Pooling Project of 19 Cohort Studies2016In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, no 8, p. 1155-1166Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20: 5 omega-3), docosapentaenoic acid (DPA; 22: 5 omega-3), and docosahexaenoic acid (DHA; 22: 6 omega-3) and plant-derived alpha-linolenic acid (ALA; 18: 3 omega-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

  • 41. Deschasaux, Melanie
    et al.
    Huybrechts, Inge
    Murphy, Neil
    Julia, Chantal
    Hercberg, Serge
    Srour, Bernard
    Kesse-Guyot, Emmanuelle
    Latino-Martel, Paule
    Biessy, Carine
    Casagrande, Corinne
    Jenab, Mazda
    Ward, Heather
    Weiderpass, Elisabete
    Dahm, Christina C.
    Overvad, Kim
    Kyro, Cecilie
    Olsen, Anja
    Affret, Aurelie
    Boutron-Ruault, Marie-Christine
    Mahamat-Saleh, Yahya
    Kaaks, Rudolf
    Kuehn, Tilman
    Boeing, Heiner
    Schwingshackl, Lukas
    Bamia, Christina
    Peppa, Eleni
    Trichopoulou, Antonia
    Masala, Giovanna
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Buen-de-Mesquita, Bas
    Peeters, Petra H.
    Hjartåker, Anette
    Rylander, Charlotta
    Skeie, Guri
    Ramon Quiros, J.
    Jakszyn, Paula
    Salamanca-Fernandez, Elena
    Maria Huerta, Jose
    Ardanaz, Eva
    Amiano, Pilar
    Ericson, Ulrika
    Sonestedt, Emily
    Huseinovic, Ena
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Khaw, Kay-Tee
    Wareham, Nick
    Bradbury, Kathryn E.
    Perez-Cornago, Aurora
    Tsilidis, Konstantinos K.
    Ferrari, Pietro
    Riboli, Elio
    Gunter, Marc J.
    Touvier, Mathilde
    Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: results from the EPIC prospective cohort study2018In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 15, no 9, article id e1002651Article in journal (Refereed)
    Abstract [en]

    Background

    Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations.

    Methods and findings

    This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out.

    Conclusions

    In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.

  • 42.
    Drobni, Mirva
    et al.
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Hallberg, K
    Öhman, Ulla
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Birve, Anna
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Persson, Karina
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Sequence analyses of fimbriae subunit FimA proteins on Actinomyces naeslundii genospecies 1 and 2 and Actinomyces odontolyticus with variant carbohydrate binding specificities.2006In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 43, no 6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Actinomyces naeslundii genospecies 1 and 2 express type-2 fimbriae (FimA subunit polymers) with variant Galbeta binding specificities and Actinomyces odontolyticus a sialic acid specificity to colonize different oral surfaces. However, the fimbrial nature of the sialic acid binding property and sequence information about FimA proteins from multiple strains are lacking. RESULTS: Here we have sequenced fimA genes from strains of A.naeslundii genospecies 1 (n = 4) and genospecies 2 (n = 4), both of which harboured variant Galbeta-dependent hemagglutination (HA) types, and from A.odontolyticus PK984 with a sialic acid-dependent HA pattern. Three unique subtypes of FimA proteins with 63.8-66.4% sequence identity were present in strains of A. naeslundii genospecies 1 and 2 and A. odontolyticus. The generally high FimA sequence identity (> 97.2%) within a genospecies revealed species specific sequences or segments that coincided with binding specificity. All three FimA protein variants contained a signal peptide, pilin motif, E box, proline-rich segment and an LPXTG sorting motif among other conserved segments for secretion, assembly and sorting of fimbrial proteins. The highly conserved pilin, E box and LPXTG motifs are present in fimbriae proteins from other Gram-positive bacteria. Moreover, only strains of genospecies 1 were agglutinated with type-2 fimbriae antisera derived from A. naeslundii genospecies 1 strain 12104, emphasizing that the overall folding of FimA may generate different functionalities. Western blot analyses with FimA antisera revealed monomers and oligomers of FimA in whole cell protein extracts and a purified recombinant FimA preparation, indicating a sortase-independent oligomerization of FimA. CONCLUSION: The genus Actinomyces involves a diversity of unique FimA proteins with conserved pilin, E box and LPXTG motifs, depending on subspecies and associated binding specificity. In addition, a sortase independent oligomerization of FimA subunit proteins in solution was indicated.

  • 43. Duarte-Salles, Talita
    et al.
    Fedirko, Veronika
    Stepien, Magdalena
    Aleksandrova, Krasimira
    Bamia, Christina
    Lagiou, Pagona
    Laursen, Anne Sofie Dam
    Hansen, Louise
    Overvad, Kim
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    His, Mathilde
    Boeing, Heiner
    Katzke, Verena
    Kühn, Tilman
    Trichopoulou, Antonia
    Valanou, Elissavet
    Kritikou, Maria
    Masala, Giovanna
    Panico, Salvatore
    Sieri, Sabina
    Ricceri, Fulvio
    Tumino, Rosario
    Bueno-de-Mesquita, H B As
    Peeters, Petra H
    Hjartåker, Anette
    Skeie, Guri
    Weiderpass, Elisabete
    Ardanaz, Eva
    Bonet, Catalina
    Chirlaque, Maria-Dolores
    Dorronsoro, Miren
    Quirós, J Ramón
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ohlsson, Bodil
    Sjöberg, Klas
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Travis, Ruth C
    Wareham, Nick
    Ferrari, Pietro
    Freisling, Heinz
    Romieu, Isabelle
    Cross, Amanda J
    Gunter, Marc
    Lu, Yunxia
    Jenab, Mazda
    Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 11, p. 2715-2728Article in journal (Refereed)
    Abstract [en]

    The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.

  • 44. Duarte-Salles, Talita
    et al.
    Fedirko, Veronika
    Stepien, Magdalena
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Trepo, Elisabeth
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Cadeau, Claire
    Kühn, Tilman
    Aleksandrova, Krasimira
    Trichopoulos, Dimitrios
    Tsiotas, Konstantinos
    Boffetta, Paolo
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H B as
    Dik, Vincent K
    Peeters, Petra H
    Weiderpass, Elisabete
    Torhild Gram, Inger
    Hjartåker, Anette
    Ramón Quirós, Jose
    Fonseca-Nunes, Ana
    Molina-Montes, Esther
    Dorronsoro, Miren
    Navarro Sanchez, Carmen
    Barricarte, Aurelio
    Lindkvist, Björn
    Sonestedt, Emily
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C
    Romieu, Isabelle
    Riboli, Elio
    Jenab, Mazda
    Dairy products and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 7, p. 1662-1672Article in journal (Refereed)
    Abstract [en]

    Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (N(cases) = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (N(cases) = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; p(trend) = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; p(trend) = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; p(trend) = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration.

  • 45. Duell, Eric J
    et al.
    Bonet, Catalina
    Muñoz, Xavier
    Lujan-Barroso, Leila
    Weiderpass, Elisabete
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Severi, Gianluca
    Canzian, Federico
    Rizzato, Cosmeri
    Boeing, Heiner
    Overvad, Kim
    Tjønneland, Anne
    Argüelles, Marcial
    Sánchez-Cantalejo, Emilio
    Chamosa, Saioa
    Huerta, José María
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Rutch C
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Yiannakouris, Nikos
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Bueno-de-Mesquita, H B As
    Siersema, Peter D
    Peeters, Petra H M
    Ohlsson, Bodil
    Lindkvist, Björn
    Johansson, Ingegerd
    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 Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Matthias
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Fenger, Claus
    Riboli, Elio
    Sala, Núria
    González, Carlos A
    Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 4, p. 880-893Article in journal (Refereed)
    Abstract [en]

    ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio = 1.84, 95%CI = 1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.

  • 46. Duell, Eric J
    et al.
    Lujan-Barroso, Leila
    Llivina, Claudia
    Muñoz, Xavier
    Jenab, Mazda
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Racine, Antoine
    Boeing, Heiner
    Buijsse, Brian
    Canzian, Federico
    Johnson, Theron
    Dalgård, Christine
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Sánchez, Soledad C
    Sánchez-Cantalejo, Emilio
    Huerta, José-María
    Ardanaz, Eva
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Travis, Ruth C
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Rafnsson, Snorri
    Palli, Domenico
    Sacerdote, Carlotta
    Tumino, Rosario
    Panico, Salvatore
    Grioni, Sara
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    Numans, Mattijs E
    Peeters, Petra H
    Johansen, Dorthe
    Lindkvist, Björn
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic Epidemiology Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Skeie, Guri
    Weiderpass, Elisabete
    Duarte-Salles, Talita
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Riboli, Elio
    Sala, Núria
    González, Carlos A
    Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort2013In: Genes & Nutrition, ISSN 1555-8932, E-ISSN 1865-3499, Vol. 8, no 6, p. 549-560Article in journal (Refereed)
    Abstract [en]

    Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11-2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.

  • 47. Duell, Eric J
    et al.
    Travier, Noémie
    Lujan-Barroso, Leila
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Palli, Domenico
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Quirós, J Ramón
    Sánchez-Cantalejo, Emilio
    Navarro, Carmen
    Gurrea, Aurelio Barricarte
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Allen, Naomi E
    Key, Timothy J
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    Numans, Mattijs E
    Peeters, Petra Hm
    Trichopoulou, Antonia
    Naska, Androniki
    Dilis, Vardis
    Teucher, Birgit
    Kaaks, Rudolf
    Boeing, Heiner
    Schütze, Madlen
    Regner, Sara
    Lindkvist, Björn
    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.
    Overvad, Kim
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Egeberg, Rikke
    Tjønneland, Anne
    Lund, Eiliv
    Weiderpass, Elisabete
    Braaten, Tonje
    Romieu, Isabelle
    Ferrari, Pietro
    Jenab, Mazda
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Aune, Dagfinn
    Norat, Teresa
    Riboli, Elio
    González, Carlos A
    Alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.2011In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 94, no 5, p. 1266-75Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer death worldwide. The association between alcohol consumption and GC has been investigated in numerous epidemiologic studies with inconsistent results.

    OBJECTIVE: We evaluated the association between alcohol consumption and GC risk.

    DESIGN: We conducted a prospective analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 444 cases of first primary gastric adenocarcinoma. HRs and 95% CIs for GC were estimated by using multivariable Cox proportional hazards regression for consumption of pure ethanol in grams per day, with stratification by smoking status, anatomic subsite (cardia, noncardia), and histologic subtype (diffuse, intestinal). In a subset of participants, results were further adjusted for baseline Helicobacter pylori serostatus.

    RESULTS: Heavy (compared with very light) alcohol consumption (≥60 compared with 0.1-4.9 g/d) at baseline was positively associated with GC risk (HR: 1.65; 95% CI: 1.06, 2.58), whereas lower consumption amounts (<60 g/d) were not. When we analyzed GC risk by type of alcoholic beverage, there was a positive association for beer (≥30 g/d; HR: 1.75; 95% CI: 1.13, 2.73) but not for wine or liquor. Associations were primarily observed at the highest amounts of drinking in men and limited to noncardia subsite and intestinal histology; no statistically significant linear dose-response trends with GC risk were observed.

    CONCLUSION: Heavy (but not light or moderate) consumption of alcohol at baseline (mainly from beer) is associated with intestinal-type noncardia GC risk in men from the EPIC cohort.

  • 48.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    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.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wiklund, Per-Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Iron stores and HFE genotypes are not related to increased risk of ischemic stroke.: a prospective nested case-referent study2007In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 24, no 5, p. 405-411Article in journal (Refereed)
    Abstract [en]

    Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke.

    Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting.

    Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke.

    Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.

  • 49.
    Eklöf, Vincy
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    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.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T polymorphisms and the risk of colorectal cancer: a nested case-referent study2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 5, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Objective. Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case‐referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T, to the risk of colorectal cancer, taking into account pre‐diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C>T polymorphism, which were analysed in a previous study.

    Material and methods. Subjects were 220 cases and 414 matched referents from the population‐based Northern Sweden Health and Disease Study.

    Results. The RFC1 80A‐allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T‐allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C>T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance.

    Conclusions. These findings suggest that although the RFC1 80G>A and FOLH1 1561C>T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.

    Read More: http://informahealthcare.com/doi/abs/10.1080/00365510701805431

  • 50.
    Eriksson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Holgerson, Pernilla Lif
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Saliva and tooth biofilm bacterial microbiota in adolescents in a low caries community2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 5861Article in journal (Refereed)
    Abstract [en]

    The oral cavity harbours a complex microbiome that is linked to dental diseases and serves as a route to other parts of the body. Here, the aims were to characterize the oral microbiota by deep sequencing in a low-caries population with regular dental care since childhood and search for association with caries prevalence and incidence. Saliva and tooth biofilm from 17-year-olds and mock bacteria communities were analysed using 16S rDNA Illumina MiSeq (v3-v4) and PacBio SMRT (v1-v8) sequencing including validity and reliability estimates. Caries was scored at 17 and 19 years of age. Both sequencing platforms revealed that Firmicutes dominated in the saliva, whereas Firmicutes and Actinobacteria abundances were similar in tooth biofilm. Saliva microbiota discriminated caries-affected from caries-free adolescents, with enumeration of Scardovia wiggsiae, Streptococcus mutans, Bifidobacterium longum, Leptotrichia sp. HOT498, and Selenomonas spp. in caries-affected participants. Adolescents with B. longum in saliva had significantly higher 2-year caries increment. PacBio SMRT revealed Corynebacterium matruchotii as the most prevalent species in tooth biofilm. In conclusion, both sequencing methods were reliable and valid for oral samples, and saliva microbiota was associated with cross-sectional caries prevalence, especially S. wiggsiae, S. mutans, and B. longum; the latter also with the 2-year caries incidence.

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