• Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study.

      Dossus, Laure; Franceschi, Silvia; Biessy, Carine; Navionis, Anne-Sophie; Travis, Ruth C; Weiderpass, Elisabete; Scalbert, Augustin; Romieu, Isabelle; Tjønneland, Anne; Olsen, Anja; et al. (2018-04-01)
      Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 = 0.69, 95% CI: 0.49-0.98, Ptrend = 0.04) but not among men (ORT3vs.T1 = 1.36, 95% CI: 0.67-2.76, Ptrend = 0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 = 1.59, 95% CI: 1.13-2.25, Ptrend = 0.01) but not in men (ORT3vs.T1 = 1.78, 95% CI: 0.80-3.98, Ptrend = 0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.
    • Association of menopausal characteristics and risk of coronary heart disease: a pan-European case-cohort analysis.

      Dam, Veerle; van der Schouw, Yvonne T; Onland-Moret, N Charlotte; Groenwold, Rolf H H; Peters, Sanne A E; Burgess, Stephen; Wood, Angela M; Chirlaque, Maria-Dolores; Moons, Karel G M; Oliver-Williams, Clare; et al. (2019-02-22)
      Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors. We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders. After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors. Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
    • Circulating insulin-like growth factor I in relation to melanoma risk in the European Prospective Investigation into Cancer and Nutrition.

      Bradbury, Kathryn E; Appleby, Paul N; Tipper, Sarah J; Travis, Ruth C; Allen, Naomi E; Kvaskoff, Marina; Overvad, Kim; Tjønneland, Anne; Halkjaer, Jytte; Cevenka, Iris; et al. (2018-09-07)
      Insulin-like growth factor (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1221 melanoma cases and 1221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity, and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth=0.93 (95% confidence interval (CI): 0.71 to 1.22)). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by sex, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma. This article is protected by copyright. All rights reserved.
    • Consumption of Fish Is Not Associated with Risk of Differentiated Thyroid Carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

      Zamora-Ros, Raul; Castañeda, Jazmín; Rinaldi, Sabina; Cayssials, Valerie; Slimani, Nadia; Weiderpass, Elisabete; Tsilidis, Konstantinos K; Boutron-Ruault, Marie-Christine; Overvad, Kim; Eriksen, Anne K; et al. (2017)
      Background: Differentiated thyroid cancer (TC) is the most common endocrine cancer. Fish can be an important source of iodine and other micronutrients and contaminants that may affect the thyroid gland and TC risk.Objective: We prospectively evaluated the relations between the consumption of total fish and different fish types and shellfish and TC risk in the EPIC (European Prospective Investigation into Cancer and Nutrition) study.Methods: EPIC is a cohort of >500,000 men and women, mostly aged 35-70 y, who were recruited in 10 European countries. After a mean follow-up of 14 y, 748 primary differentiated TC cases were diagnosed; 666 were in women and 601 were papillary TC. Data on intakes of lean fish, fatty fish, fish products, and shellfish were collected by using country-specific validated dietary questionnaires at recruitment. Multivariable Cox regression was used to calculate HRs and 95% CIs adjusted for many potential confounders, including dietary and nondietary factors.Results: No significant association was observed between total fish consumption and differentiated TC risk for the highest compared with the lowest quartile (HR: 1.03; 95% CI: 0.81, 1.32; P-trend = 0.67). Likewise, no significant association was observed with the intake of any specific type of fish, fish product, or shellfish. No significant heterogeneity was found by TC subtype (papillary or follicular tumors), by sex, or between countries with low and high TC incidence.Conclusion: This large study shows that the intake of fish and shellfish was not associated with differentiated TC risk in Europe, a region in which iodine deficiency or excess is rare.
    • Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease.

      Key, Timothy J; Appleby, Paul N; Bradbury, Kathryn E; Sweeting, Michael; Wood, Angela; Johansson, Ingegerd; Kühn, Tilman; Steur, Marinka; Weiderpass, Elisabete; Wennberg, Maria; et al. (2019-06-18)
    • Dietary folate intake and pancreatic cancer risk: Results from the European Prospective Investigation into Cancer and Nutrition.

      Park, Jin Young; Bueno-de-Mesquita, H Bas; Ferrari, Pietro; Weiderpass, Elisabete; de Batlle, Jordi; Tjønneland, Anne; Kyro, Cecilie; Rebours, Vinciane; Boutron-Ruault, Marie-Christine; Mancini, Francesca Romana; et al. (2018-09-04)
      Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded. Folate intake was energy-adjusted using the residual method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In multivariable analyses stratified by age, sex, study centre and adjusted for energy intake, smoking status, BMI, educational level, diabetes status, supplement use and dietary fibre intake, we found no significant association between folate intake and PC risk: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/d) compared with the lowest (<241 μg/d) was 0.81 (95% CI: 0.51, 1.31; Ptrend = 0.38). In current smokers, a positive trend was observed in PC risk across folate quartiles (HR=4.42 (95% CI: 1.05, 18.62) for ≥353 μg/d vs. <241 μg/d, Ptrend = 0.01). Nonetheless, there was no significant interaction between smoking and dietary folate intake (Pinteraction = 0.99). We found no association between dietary folate intake and PC risk in this large European study. This article is protected by copyright. All rights reserved.
    • Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

      Ward, Heather A; Whitman, Julia; Muller, David C; Johansson, Mattias; Jakszyn, Paula; Weiderpass, Elisabete; Palli, Domenico; Fanidi, Anouar; Vermeulen, Roel; Tjønneland, Anne; et al. (2018-10-18)
      Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding.
    • Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study.

      Murphy, Neil; Ward, Heather A; Jenab, Mazda; Rothwell, Joseph A; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Kvaskoff, Marina; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; et al. (2018-07-26)
      Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most have been of insufficient size to identify heterogeneous associations with precision.
    • Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

      Agudo, Antonio; Cayssials, Valerie; Bonet, Catalina; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Affret, Aurélie; Fagherazzi, Guy; Katzke, Verena; Schübel, Ruth; et al. (2018-04-01)
      Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation.
    • Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort.

      Fortner, Renée T; Schock, Helena; Le Cornet, Charlotte; Hüsing, Anika; Vitonis, Allison F; Johnson, Theron S; Fichorova, Raina N; Fashemi, Titilayo; Yamamoto, Hidemi S; Tjønneland, Anne; et al. (2018-04-01)
      CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; phet = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.
    • Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort.

      Aleksandrova, Krasimira; Jenab, Mazda; Leitzmann, Michael; Bueno-de-Mesquita, Bas; Kaaks, Rudolf; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Rinaldi, Sabina; Freisling, Heinz; et al. (2017-12-01)
      There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer.