Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
Aleksandrova, K. ; Jenab, M. ; Bueno-de-Mesquita, H.B. ; Fedirko, V. ; Kaaks, R. ; Lukanova, A. ; Duijnhoven, F.J.B. van - \ 2014
European Journal of Epidemiology 29 (2014)4. - ISSN 0393-2990 - p. 261 - 275.
soluble leptin receptor - density-lipoprotein cholesterol - c-reactive protein - insulin-resistance - oxidative stress - hdl-cholesterol - multiple imputation - plasma adiponectin - binding-proteins - adipose-tissue
A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.
Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort
Dossus, L. ; Boutron-Ruault, M.C. ; Kaaks, R. ; Gram, I.T. ; Vilier, A. ; Fervers, B. ; Manjer, J. ; Tjonneland, A. ; Olsen, A. ; Overvad, K. ; Chang-Claude, J. ; Boeing, H. ; Steffen, A. ; Trichopoulou, A. ; Lagiou, P. ; Sarantopoulou, M. ; Palli, D. ; Berrino, F. ; Tumino, R. ; Vineis, P. ; Mattiello, A. ; Bueno-de-Mesquita, H.B. ; Duijnhoven, F.J.B. van - \ 2014
International Journal of Cancer 134 (2014)8. - ISSN 0020-7136 - p. 1871 - 1888.
environmental tobacco-smoke - postmenopausal women - california teachers - 1st childbirth - never smokers - exposure - metaanalysis - association - carcinogens - reanalysis
Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05–1.28], 1.14 [1.04–1.25] and 1.10 [1.01–1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29–2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34–0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.
Smoking and long-term risk of type 2 Diabetes: The EPIC-InterAct Study in European populations
The InterAct Consortium, A. ; Spijkerman, A.M.W. ; A, D.L. van der; Nilsson, P. ; Balkau, B. ; Beulens, J.W.J. ; Boeing, H. ; Feskens, E.J.M. ; Kaaks, R. - \ 2014
Diabetes Care 37 (2014)12. - ISSN 0149-5992 - p. 3164 - 3171.
kora s4/f4 cohort - middle-aged men - cigarette-smoking - insulin-resistance - physical-activity - fat distribution - active smoking - mellitus - women - glucose
OBJECTIVE The aims of this study were to investigate the association between smoking and incident type 2 diabetes, accounting for a large number of potential confounding factors, and to explore potential effect modifiers and intermediate factors. RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct is a prospective case-cohort study within eight European countries, including 12,403 cases of incident type 2 diabetes and a random subcohort of 16,835 individuals. After exclusion of individuals with missing data, the analyses included 10,327 cases and 13,863 subcohort individuals. Smoking status was used (never, former, current), with never smokers as the reference. Country-specific Prentice-weighted Cox regression models and random-effects meta-analysis were used to estimate hazard ratios (HRs) for type 2 diabetes. RESULTS In men, the HRs (95% CI) of type 2 diabetes were 1.40 (1.26, 1.55) for former smokers and 1.43 (1.27, 1.61) for current smokers, independent of age, education, center, physical activity, and alcohol, coffee, and meat consumption. In women, associations were weaker, with HRs (95% CI) of 1.18 (1.07, 1.30) and 1.13 (1.03, 1.25) for former and current smokers, respectively. There was some evidence of effect modification by BMI. The association tended to be slightly stronger in normal weight men compared with those with overall adiposity. CONCLUSIONS Former and current smoking was associated with a higher risk of incident type 2 diabetes compared with never smoking in men and women, independent of educational level, physical activity, alcohol consumption, and diet. Smoking may be regarded as a modifiable risk factor for type 2 diabetes, and smoking cessation should be encouraged for diabetes prevention.
Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
Rohrmann, S. ; Linseisen, J. ; Allen, N. ; Bueno-de-Mesquita, H.B. ; Johnsen, N.F. ; Tjonneland, A. ; Overvad, K. ; Kaaks, R. ; Teucher, B. ; Boeing, H. ; Pischon, T. ; Lagiou, P. ; Trichopoulou, A. ; Trichopoulos, D. ; Palli, D. ; Krogh, V. ; Tunnino, R. ; Ricceri, F. ; Suarez, M.V.A. ; Agudo, A. ; Sanchez, M.J. ; Chirlaque, M.D. ; Barricarte, A. ; Larranaga, N. ; Boshuizen, H.C. ; Kranen, H.J. ; Stettin, P. ; Johansson, M. ; Bjartell, A. ; Ulmert, D. ; Khaw, K.T. ; Wareham, N.J. ; Ferrari, P. ; Romieux, I. ; Gunter, M.J.R. ; Riboli, E. ; Key, T.J. - \ 2013
British Journal of Cancer 108 (2013)3. - ISSN 0007-0920 - p. 708 - 714.
cigarette-smoking - follow-up - health-professionals - prospective us - tobacco use - cohort - men - recurrence - association - mortality
Background: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. Methods: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. Results: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR = 0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR = 1.81, 95% CI: 1.11-2.93; RR = 1.38, 95% CI: 1.01-1.87, respectively). Conclusion: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.
Plasma 25(OH)vitamin D and the risk of breast cancer in the european prospective investigation into cancer and nutrition (EPIC): A nested case-control study
Kühn, T. ; Kaaks, R. ; Becker, S. ; Eomois, P.P. ; Clavel-Chapelon, F. ; Kvaskoff, M. ; Dossus, L. ; Duijnhoven, F.J.B. van - \ 2013
International Journal of Cancer 133 (2013)7. - ISSN 0020-7136 - p. 1689 - 1700.
d-binding protein - circulating vitamin-d - french e3n cohort - postmenopausal women - nurses health - serum-levels - association - prevention - calcium - time
Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. Although the results of case–control studies indicate that circulating 25-hydroxyvitamin D [25(OH)D] is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case–control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out comprising 1,391 incident breast cancer cases and 1,391 controls. Multivariable conditional logistic regression models did not reveal a significant overall association between season-standardized 25(OH)D levels and the risk of breast cancer (ORQ4–Q1 [95% CI]: 1.07 [0.85–1.36], ptrend = 0.67). Moreover, 25(OH)D levels were not related to the risks of estrogen receptor positive tumors (ORQ4–Q1 [95% CI]: 0.97 [0.67–1.38], ptrend = 0.90) and estrogen receptor negative tumors (ORQ4–Q1 [95% CI]: 0.97 [0.66–1.42], ptrend = 0.98). In hormone replacement therapy (HRT) users, 25(OH)D was significantly inversely associated with incident breast cancer (ORlog2 [95% CI]: 0.62 [0.42–0.90], p = 0.01), whereas no significant association was found in HRT nonusers (ORlog2 [95% CI]: 1.14 [0.80–1.62], p = 0.48). Further, a nonsignificant inverse association was found in women with body mass indices (BMI) <25 kg/m2 (ORlog2 [95% CI]: 0.83 [0.67–1.03], p = 0.09), as opposed to a borderline significant positive association in women with BMI = 25 kg/m2 (ORlog2 [95% CI]: 1.30 [1.0–1.69], p = 0.05). Overall, prediagnostic levels of circulating 25(OH)D were not related to the risk of breast cancer in the EPIC study. This result is in line with findings in the majority of prospective studies and does not support a role of vitamin D in the development of breast cancer
Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition
Luczynska, A. ; Kaaks, R. ; Rohrmann, S. ; Becker, S. ; Linseisen, J. ; Buijsse, B. ; Duijnhoven, F.J.B. van - \ 2013
American Journal of Clinical Nutrition 98 (2013)3. - ISSN 0002-9165 - p. 827 - 838.
non-hodgkin-lymphoma - chronic lymphocytic-leukemia - vitamin-d status - sun exposure - ultraviolet-radiation - subsequent risk - infections - disease - supplementation - association
Background: The relation between vitamin D status and lymphoma risk is inconclusive. Objective: We examined the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] and lymphoid cancer risk. Design: We conducted a study nested within the European Prospective Investigation into Cancer and Nutrition cohort of 1127 lymphoma cases and 1127 matched controls with a mean follow-up time of 7.1 y. Conditional logistic regression was used to estimate multivariable-adjusted incidence rate ratios of lymphoma risk in relation to plasma 25(OH)D. Season-standardized and season-specific 25(OH)D quartiles were used. We also analyzed 25(OH)D as a continuous variable and used predefined cutoffs. Results: No statistically significant association between plasma 25(OH)D and overall lymphoid cancer risk was observed. A positive association for B-cell non-Hodgkin lymphoma was noted only in those with a diagnosis made during the first 2 y of follow-up (P-heterogeneity = 0.03), which suggests the possibility of reverse causality. Further analysis restricted to participants with =2 y of follow-up time showed a significant association between 25(OH)D and chronic lymphocytic leukemia (CLL) (n = 161): adjusted incidence rate ratios were 0.40 (95% CI: 0.18, 0.90; P-trend = 0.05) and 0.31 (95% CI: 0.13, 0.76; P-trend = 0.03) for the top compared with the bottom season-standardized and season-specific quartiles, respectively. Data on dietary vitamin D intake provided further support for the observed association (incidence rate ratio: 0.33; 95% CI = 0.12, 0.89; P-trend = 0.006). Conclusions: Our findings do not support a protective role of high 25(OH)D concentration in lymphoid cancers overall. However, they suggest that higher concentrations of 25(OH)D are associated with a reduced risk of CLL.
Dietary Fibre Intake and Risks of Cancers of the Colon and Rectum in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Murphy, N. ; Norat, T. ; Ferrari, P. ; Jenab, M. ; Bueno-de-Mesquita, B. ; Skeie, G. ; Dahm, C.C. ; Overvad, K. ; Olsen, A. ; Tjonneland, A. ; Clavel-Chapelon, F. ; Boutron-Ruault, M.C. ; Racine, A. ; Kaaks, R. ; Teucher, B. ; Boeing, H. ; Bergmann, M.M. ; Trichopoulou, A. ; Trichopoulos, D. ; Lagiou, P. ; Palli, D. ; Pala, V. ; Panico, S. ; Tumino, R. ; Vineis, P. ; Siersema, P. ; Duijnhoven, F.J.B. van; Peeters, P.H.M. ; Hjartaker, A. ; Engeset, D. ; Gonzalez, C.A. ; Sanchez, M.J. ; Dorronsoro, M. ; Navarro, C. ; Ardanaz, E. ; Quiros, J.R. ; Sonestedt, E. ; Ericson, U. ; Nilsson, L. ; Palmqvist, R. ; Khaw, K.T. ; Wareham, N. ; Key, T.J. ; Crowe, F.L. ; Fedirko, V. ; Wark, P.A. ; Chuang, S.C. ; Riboli, E. - \ 2012
PLoS ONE 7 (2012)6. - ISSN 1932-6203
colorectal-cancer - nonstarch polysaccharides - epidemiologic evidence - measurement error - glycemic index - cohort - project - carbohydrate - calibration - protection
Background: Earlier analyses within the EPIC study showed that dietary fibre intake was inversely associated with colorectal cancer risk, but results from some large cohort studies do not support this finding. We explored whether the association remained after longer follow-up with a near threefold increase in colorectal cancer cases, and if the association varied by gender and tumour location. Methodology/Principal Findings: After a mean follow-up of 11.0 years, 4,517 incident cases of colorectal cancer were documented. Total, cereal, fruit, and vegetable fibre intakes were estimated from dietary questionnaires at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models stratified by age, sex, and centre, and adjusted for total energy intake, body mass index, physical activity, smoking, education, menopausal status, hormone replacement therapy, oral contraceptive use, and intakes of alcohol, folate, red and processed meats, and calcium. After multivariable adjustments, total dietary fibre was inversely associated with colorectal cancer (HR per 10 g/day increase in fibre 0.87, 95% CI: 0.79-0.96). Similar linear associations were observed for colon and rectal cancers. The association between total dietary fibre and risk of colorectal cancer risk did not differ by age, sex, or anthropometric, lifestyle, and dietary variables. Fibre from cereals and fibre from fruit and vegetables were similarly associated with colon cancer; but for rectal cancer, the inverse association was only evident for fibre from cereals. Conclusions/Significance: Our results strengthen the evidence for the role of high dietary fibre intake in colorectal cancer prevention.
Prospective study on physical activity and risk of in situ breast cancer
Steindorf, K. ; Ritte, R. ; Tjonneland, A. ; Johnsen, N.F. ; Overvad, K. ; Ostergaard, J.N. ; Boeing, H. ; Trichopoulou, A. ; Bueno de Mesquita, H.B. ; Duijnhoven, F.J.B. van; Monninkhof, E.M. ; Khaw, K.T. ; Wareham, N.J. ; Wark, P.A. ; Riboli, E. ; Kaaks, R. - \ 2012
Cancer Epidemiology Biomarkers and Prevention 21 (2012)12. - ISSN 1055-9965 - p. 2209 - 2219.
postmenopausal women - activity questionnaire - biologic mechanisms - ductal carcinoma - nutrition - validity - repeatability - exercise - cohort
Background: Physical activity has been identified as protective factor for invasive breast cancer risk, whereas comparable studies on in situ carcinoma are rare. Methods: The study included data from 283,827 women of the multinational European Prospective Investigation into C7ancer and Nutrition (EPIC)-cohort study. Detailed information on different types of physical activity conducted during the prior year, such as occupational, recreational, and household activity, as well as on important cofactors, was assessed at baseline. Adjusted HRs for in situ breast cancer were estimated by Cox proportional hazards models. Results: During a median follow-up period of 11.7 years, 1,059 incidents of breast carcinoma in situ were identified, in crude and adjusted multivariable models, no associations were found for occupational, household, and recreational physical activity. Furthermore, total physical activity was not associated with risk of in situ breast cancer. Comparing moderately inactive, moderately active, and active participants with inactive study participants resulted in adjusted HRs of 0.99 [95% confidence interval (CI), 0.83-1.19], 0.99 (95% CI, 0.82-1.20), and 1.07(95% CI, 0.81-1.40), respectively (P value of trend test: 0.788). No inverse associations were found in any substrata defined by age at diagnosis or body mass index (BMI) status. Conclusions: In this large prospective study, we did not find any evidence of an association between physical activity and in situ breast cancer risk. It not by chance, the contrast between our results for carcinoma in situ and the recognized inverse association for invasive breast cancer suggests that physical activity may have stronger effects on proliferation and late stage carcinogenesis. Cancer Epidemiol Biomarkers Prev; 21(12); 2209-19. (C)2012 AACR.
Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European prospective investigation into cancer and nutrition
Ros, M. ; Bueno-de-Mesquita, H.B. ; Kampman, E. ; Büchner, F.L. ; Aben, K.K. ; Egevad, L. ; Overvad, K. ; Tjonneland, A. ; Roswall, N. ; Clavel-Chapelon, F. ; Boutron-Ruault, M.C. ; Moiros, S. ; Kaaks, R. ; Teucher, B. ; Weikert, S. ; Ruesten, A.V. ; Trichopoulou, A. ; Naska, A. ; Benetou, V. ; Saieva, C. ; Pala, V. ; Ricceri, F. ; Tumino, R. ; Mattiello, A. ; Peeters, P.H.M. ; Gils, C.H. van; Gram, I.T. ; Engeset, D. ; Chirlaque, M.D. ; Ardanazx, E. ; Rodriguez, L. - \ 2012
European Journal of Cancer 48 (2012)17. - ISSN 0959-8049 - p. 3267 - 3277.
bladder-cancer - vitamin-c - prospective cohort - carotenoids - smoking - diet - carcinogenesis - prevention - nutrient - folate
Background - Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods - After 8.9 years of follow-up, 947 UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. Results - Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.78–1.00 and HR 0.87; 95% CI 0.77–0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95% CI 0.77–0.98). Conclusion - Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded.
Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location
Leufkens, A.M. ; Duijnhoven, F.J.B. van; Boshuizen, H.C. ; Sierseman, P.D. ; Kunst, A.E. ; Mouw, T. ; Tjonneland, A. ; Olsen, A. ; Overvad, K. ; Boutron-Ruault, M.C. ; Clavel-Chapelon, F. ; Morois, S. ; Krogh, V. ; Tumino, R. ; Panico, S. ; Polidoro, S. ; Palli, D. ; Kaaks, R. ; Teucher, B. ; Pischon, T. ; Trichopoulou, A. ; Orfanos, P. ; Goufa, I. ; Peeters, P.H. ; Skeie, G. ; Braaten, T. ; Rodriguez, L. ; Lujan-Barroso, L. ; Sanchez-Perez, M.J. ; Navarro, C. ; Barricarte, A. ; Zackrisson, S. ; Almquist, M. ; Hallmans, G. ; Palmqvist, R. ; Tsilidis, K.K. ; Khaw, K.T. ; Wareham, N. ; Gallo, V. ; Jenab, M. ; Riboli, E. ; Bueno-de-Mesquita, H.B. - \ 2012
International Journal of Cancer 130 (2012)3. - ISSN 0020-7136 - p. 622 - 630.
socioeconomic-status - united-states - nutrition - colon - survival - health - women - inequalities - deprivation - rectum
Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57–0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58–0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe
Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European prospective investigation into cancer and nutrition
Jeurnink, S.M. ; Büchner, F.L. ; Bueno-de Mesquita, H.B. ; Siersema, P.D. ; Boshuizen, H.C. ; Numans, M.E. ; Dahm, C.C. ; Overvad, K. ; Tjonneland, A. ; Roswall, N. ; Clavel-Chapelon, F. ; Boutron-Ruault, M.C. ; Morois, S. ; Kaaks, R. ; Teucher, B. ; Boeing, H. ; Buijsse, B. ; Trichopoulou, A. ; Benetou, V. ; Zylis, D. ; Palli, D. ; Sieri, S. ; Vineis, P. ; Tumino, R. ; Panico, S. ; Ocké, M.C. ; Peeters, P.H. ; Skeie, G. ; Brustad, M. ; Lund, E. ; Sanchez-Cantalejo, E. ; Navarro, C. ; Amiano, P. ; Ardanaz, E. ; Ramón Quirós, J. ; Hallmans, G. ; Johansson, I. ; Lindkvist, B. ; Regnér, S. ; Khaw, K.T. ; Wareham, N. ; Key, T.J. ; Slimani, N. ; Norat, T. ; Vergnaud, A.C. ; Romaguera, D. ; Gonzalez, C.A. - \ 2012
International Journal of Cancer 131 (2012)6. - ISSN 0020-7136 - p. E963 - E973.
epic-eurgast - epidemiologic evidence - helicobacter-pylori - physical-activity - diet diversity - cereal fiber - vitamin-c - stomach - adenocarcinomas - metaanalysis
Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow-up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79–0.97 and 0.76; 95% CI 0.62–0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded
A risk model for lung cancer incidence
Hoggart, C. ; Brennan, P. ; Tjonneland, A. ; Vogel, U. ; Overvad, K. ; Ostergaard, J.N. ; Kaaks, R. ; Canzian, F. ; Boeing, H. ; Steffen, A. ; Trichopoulou, A. ; Bamia, C. ; Trichopoulos, D. ; Johansson, M. ; Palli, D. ; Krogh, V. ; Tumino, R. ; Sacerdote, C. ; Panico, S. ; Boshuizen, H.C. ; Bueno-de-Mesquita, H.B. ; Peeters, P.H. ; Lund, E. ; Gram, I.T. ; Braaten, T. ; Rodrígues, L. ; Agudo, A. ; Sánchez-Cantalejo, E. ; Arriola, L. ; Chirlaque, M.D. ; Barricarte, A. ; Rasmuson, T. ; Khaw, K.T. ; Wareham, N. ; Allen, N.E. ; Riboli, E. ; Vineis, P. - \ 2012
Cancer Prevention Research / American Association for Cancer Research 5 (2012)6. - ISSN 1940-6207 - p. 834 - 846.
body-mass index - susceptibility locus - smoking-cessation - cigarette-smoking - prediction model - smokers - mortality - women - association - 5p15.33
Risk models for lung cancer incidence would be useful for prioritizing individuals for screening and participation in clinical trials of chemoprevention. We present a risk model for lung cancer built using prospective cohort data from a general population which predicts individual incidence in a given time period. We build separate risk models for current and former smokers using 169,035 ever smokers from the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) and considered a model for never smokers. The data set was split into independent training and test sets. Lung cancer incidence was modeled using survival analysis, stratifying by age started smoking, and for former smokers, also smoking duration. Other risk factors considered were smoking intensity, 10 occupational/environmental exposures previously implicated with lung cancer, and single-nucleotide polymorphisms at two loci identified by genome-wide association studies of lung cancer. Individual risk in the test set was measured by the predicted probability of lung cancer incidence in the year preceding last follow-up time, predictive accuracy was measured by the area under the receiver operator characteristic curve (AUC). Using smoking information alone gave good predictive accuracy: the AUC and 95% confidence interval in ever smokers was 0.843 (0.810-0.875), the Bach model applied to the same data gave an AUC of 0.775 (0.737-0.813). Other risk factors had negligible effect on the AUC, including never smokers for whom prediction was poor. Our model is generalizable and straightforward to implement. Its accuracy can be attributed to its modeling of lifetime exposure to smoking.
Bias in protein and potassium intake collected with 24-h recalls (EPIC-Soft) is rather comparable across European populations
Crispim, S.P. ; Geelen, A. ; Freisling, H. ; Souverein, O.W. ; Hulshof, P.J.M. ; Ocke, M.C. ; Boshuizen, H.C. ; Andersen, L.F. ; Ruprich, J. ; Keizer, W. de; Huybrechts, I. ; Lafay, L. ; DeMagistris, M.S. ; Ricceri, F. ; Tumino, R. ; Krogh, V. ; Bueono-de-Mesquita, H.B. ; Beulens, J.W.J. ; Boutron-Ruault, M.C. ; Naska, A. ; Crowe, F.L. ; Boeing, H. ; McTaggart, A.R. ; Kaaks, R. ; Veer, P. van 't; Slimani, N. - \ 2012
European Journal of Nutrition 51 (2012)8. - ISSN 1436-6207 - p. 997 - 1010.
consumption validation efcoval - diet recall - urinary nitrogen - nutrition - cancer - calibration - telephone - countries - biomarker - centers
Purpose: We investigated whether group-level bias of a 24-h recall estimate of protein and potassium intake, as compared to biomarkers, varied across European centers and whether this was influenced by characteristics of individuals or centers. Methods: The combined data from EFCOVAL and EPIC studies included 14 centers from 9 countries (n = 1,841). Dietary data were collected using a computerized 24-h recall (EPIC-Soft). Nitrogen and potassium in 24-h urine collections were used as reference method. Multilevel linear regression analysis was performed, including individual-level (e.g., BMI) and center-level (e.g., food pattern index) variables. Results: For protein intake, no between-center variation in bias was observed in men while it was 5.7% in women. For potassium intake, the between-center variation in bias was 8.9% in men and null in women. BMI was an important factor influencing the biases across centers (p <0.01 in all analyses). In addition, mode of administration (p = 0.06 in women) and day of the week (p = 0.03 in men and p = 0.06 in women) may have influenced the bias in protein intake across centers. After inclusion of these individual variables, between-center variation in bias in protein intake disappeared for women, whereas for potassium, it increased slightly in men (to 9.5%). Center-level variables did not influence the results. Conclusion: The results suggest that group-level bias in protein and potassium (for women) collected with 24-h recalls does not vary across centers and to a certain extent varies for potassium in men. BMI and study design aspects, rather than center-level characteristics, affected the biases across centers
Cigarette smoking and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.
Leufkens, A.M. ; Duijnhoven, F.J.B. van; Siersema, P.D. ; Boshuizen, H.C. ; Vrieling, A. ; Agudo, A. ; Gram, I.T. ; Weiderpass, E. ; Dahm, C. ; Overvad, K. ; Tjonneland, A. ; Olsen, A. ; Boutron-Ruault, M.C. ; Clavel-Chapelon, F. ; Morois, S. ; Palli, D. ; Grioni, S. ; Tumino, R. ; Sacerdote, C. ; Mattiello, A. ; Herman, S. ; Kaaks, R. ; Steffen, A. ; Boeing, H. ; Trichopoulou, A. ; Lagiou, P. ; Trichopoulos, D. ; Peeters, P.H. ; Gils, C.H. van; Kranen, H. van; Lund, E. ; Dumeaux, V. ; Engeset, D. ; Rodriguez, L. ; Sanchez, M.J. ; Chirlaque, M.D. ; Barricarte, A. ; Manjer, J. ; Almquist, M. ; Guelpen, B. ; Hallmans, G. ; Khaw, K.T. ; Wareham, N. ; Tsilidis, K.K. ; Straif, K. ; Leon-Roux, M. ; Vineis, P. ; Norat, T. ; Riboli, E. ; Bueno-de-Mesquita, H.B. - \ 2011
Clinical Gastroenterology and Hepatology 9 (2011)2. - ISSN 1542-3565 - p. 137 - 144.
tumor microsatellite instability - life-style factors - alcohol-consumption - rectal-cancer - colon tumors - cohort - women - polymorphisms - associations - metaanalysis
BACKGROUND & AIMS: There has been consistent evidence for a relationship between smoking and colorectal cancer (CRC), although it is not clear whether the colon or rectum is more sensitive to the effects of smoking. We investigated the relationships between cigarette smoking and risk of CRC and tumor location. METHODS: We analyzed data from 465,879 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study; 2741 developed CRC during the follow-up period (mean, 8.7 years). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The risk of colon carcinoma was increased among ever smokers (HR, 1.18; 95% CI, 1.06-1.32) and former cigarette smokers (HR, 1.21; 95% CI, 1.08-1.36), compared with never smokers; the increased risk for current smokers was of borderline significance (HR, 1.13; 95% CI, 0.98-1.31). When stratified for tumor location, the risk of proximal colon cancer was increased for former (HR, 1.25; 95% CI, 1.04-1.50) and current smokers (HR, 1.31; 95% CI, 1.06-1.64), but the risks for cancers in the distal colon or rectum were not. Subsite analyses showed a nonsignificant difference between the proximal and distal colon (P = .45) for former smokers and a significant difference for current smokers (P = .02). For smokers who had stopped smoking for at least 20 years, the risk of developing colon cancer was similar to that of never smokers. CONCLUSIONS: Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.
Consumption of meat and fish and risk of lung cancer: results from the European Prospective Investigation into Cancer and Nutrition
Linseisen, J. ; Rohrmann, S. ; Bueno-de-Mesquita, B. ; Büchner, F.L. ; Boshuizen, H.C. ; Agudo, A. ; Gram, I.T. ; Dahm, C.C. ; Overvad, K. ; Egeberg, R. ; Tjonneland, A. ; Boeing, H. ; Steffen, A. ; Kaaks, R. ; Lukanova, A. ; Berrino, F. ; Palli, D. ; Panico, S. ; Tumino, R. ; Ardanaz, E. ; Dorronsoro, M. ; Huerta, J.M. ; Rodríguez, L. ; Sánchez, M.J. ; Rasmuson, T. ; Hallmans, G. ; Manjer, J. ; Wirfält, E. ; Engeset, D. ; Skeie, G. ; Katsoulis, M. ; Oikonomou, E. ; Trichopoulou, A. ; Peeters, P.H. ; Khaw, K.T. ; Wareham, N. ; Allen, N. ; Key, T. ; Brennan, P. ; Romieu, I. ; Slimani, N. ; Vergnaud, A.C. ; Xun, W.W. ; Vineis, P. ; Riboli, E. - \ 2011
Cancer Causes and Control 22 (2011)6. - ISSN 0957-5243 - p. 909 - 918.
heterocyclic amines - dietary habits - heme iron - women - calibration - cohort - recalls - mortality - mutagens - fat
Evidence from case–control studies, but less so from cohort studies, suggests a positive association between meat intake and risk of lung cancer. Therefore, this association was evaluated in the frame of the European Prospective Investigation into Cancer and Nutrition, EPIC. Data from 478,021 participants, recruited from 10 European countries, who completed a dietary questionnaire in 1992–2000 were evaluated; 1,822 incident primary lung cancer cases were included in the present evaluation. Relative risk estimates were calculated for categories of meat intake using multi-variably adjusted Cox proportional hazard models. In addition, the continuous intake variables were calibrated by means of 24-h diet recall data to account for part of the measurement error. There were no consistent associations between meat consumption and the risk of lung cancer. Neither red meat (RR = 1.06, 95% CI 0.89–1.27 per 50 g intake/day; calibrated model) nor processed meat (RR = 1.13, 95% CI 0.95–1.34 per 50 g/day; calibrated model) was significantly related to an increased risk of lung cancer. Also, consumption of white meat and fish was not associated with the risk of lung cancer. These findings do not support the hypothesis that a high intake of red and processed meat is a risk factor for lung cancer
Dietary glycaemic index and glycaemic load in the European prospective investigation into cancer and nutrition
Bakel, M.M. van; Kaaks, R. ; Feskens, E.J.M. ; Rohrmann, S. ; Welch, A.A. ; Pala, V. ; Avloniti, K. ; Schouw, Y.T. van der; A, A.D. van der; Du, H. ; Halkjaer, J. ; Tormo, M.J. - \ 2009
European Journal of Clinical Nutrition 63 (2009)4. - ISSN 0954-3007 - p. S188 - S205.
middle-aged women - dependent diabetes-mellitus - breast-cancer - epic project - risk - carbohydrate - calibration - health - fiber - metaanalysis
Objectives: To describe dietary glycaemic index (GI) and glycaemic load (GL) values in the population participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study according to food groups, nutrients and lifestyle characteristics. Methods: Single 24-h dietary recalls (24-HDRs) from 33¿566 subjects were used to calculate dietary GI and GL, and an ad hoc database was created as the main reference source. Mean GI and GL intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. Results: GI was the lowest in Spain and Germany, and highest in the Netherlands, United Kingdom and Denmark for both genders. In men, GL was the lowest in Spain and Germany and highest in Italy, whereas in women, it was the lowest in Spain and Greece and highest in the UK health-conscious cohort. Bread was the largest contributor to GL in all centres (15–45%), but it also showed the largest inter-individual variation. GL, but not GI, tended to be lower in the highest body mass index category in both genders. GI was positively correlated with starch and intakes of bread and potatoes, whereas it was correlated negatively with intakes of sugar, fruit and dairy products. GL was positively correlated with all carbohydrate components and intakes of cereals, whereas it was negatively correlated with fat and alcohol and with intakes of wine, with large variations across countries. Conclusions: GI means varied modestly across countries and genders, whereas GL means varied more, but it may possibly act as a surrogate of carbohydrate intake.
EPIC-Heart: The cardiovascular component of a prospective study of nutritional, lifestyle and biological factors in 520,000 middle-aged participants from 10 European countries
Danesh, J. ; Saracci, R. ; Berglund, G. ; Feskens, E.J.M. ; Overvad, K. ; Panico, S. ; Thompson, S. ; Fournier, A. ; Clavel-Chapelon, F. ; Canonico, M. ; Kaaks, R. ; Linseisen, J. ; Boeing, H. ; Pischon, T. ; Weikert, C. ; Olsen, A. ; Tjonneland, A. ; Johnsen, S.P. ; Jensen, M.K. ; Quiros, J.R. ; Gonzalez-Svatetz, C.A. ; Sanchez-Perez, M.J. ; Larranaga, N. ; Navarro Sanchez, C. ; Moreno Iribas, C. ; Bingham, S. ; Khaw, K.T. ; Wareham, N. ; Key, T. ; Roddam, A. ; Trichopoulou, A. ; Benetou, V. ; Trichopoulous, D. ; Masala, G. ; Sieri, S. ; Tumino, R. ; Sacerdote, C. ; Mattiello, A. ; Verschuren, W.M.M. ; Bueno de Mesquita, H.B. ; Grobbee, D.E. ; Schouw, Y.T. van der; Melander, O. ; Hallmans, G. ; Wennberg, P. ; Lund, E. ; Kumle, M. ; Skeie, G. ; Ferrari, P. ; Slimani, N. ; Norat, T. ; Riboli, E. - \ 2007
European Journal of Epidemiology 22 (2007)2. - ISSN 0393-2990 - p. 129 - 141.
coronary-artery-disease - dietary assessment methods - high blood-pressure - fat distribution - norfolk cohort - plasma-levels - cancer - risk - women - population
EPIC-Heart is the cardiovascular component of the European Prospective Investigation into Cancer and Nutrition (EPIC), a multi-centre prospective cohort study investigating the relationship between nutrition and major chronic disease outcomes. Its objective is to advance understanding about the separate and combined influences of lifestyle (especially dietary), environmental, metabolic and genetic factors in the development of cardiovascular diseases by making best possible use of the unusually informative database and biological samples in EPIC. Between 1992 and 2000, 519,978 participants (366,521 women and 153,457 men, mostly aged 35¿70 years) in 23 centres in 10 European countries commenced follow-up for cause- specific mortality, cancer incidence and major cardiovascular morbidity. Dietary information was collected with quantitative questionnaires or semi-quantitative food frequency questionnaires, including a 24-h dietary recall sub-study to help calibrate the dietary measurements. Information was collected on physical activity, tobacco smoking, alcohol consumption, occupational history, socio-economic status, and history of previous illnesses. Anthropometric measurements and blood pressure recordings were made in the majority of participants. Blood samples were taken from 385,747 individuals, from which plasma, serum, red cells, and buffy coat fractions were separated and aliquoted for long-term storage. By 2004, an estimated 10,000 incident fatal and non-fatal coronary and stroke events had been recorded. The first cycle of EPIC-Heart analyses will assess associations of coronary mortality with several prominent dietary hypotheses and with established cardiovascular risk factors. Subsequent analyses will extend this approach to non-fatal cardiovascular outcomes¿and to further dietary, biochemical and genetic factors.
European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics
Slimani, N. ; Kaaks, R. ; Ferrari, P. ; Casagrande, C. ; Clavel-Chapelon, F. ; Lotze, G. ; Kroke, A. ; Trichopoulos, D. ; Trichopoulou, A. ; Lauria, C. ; Bellegotti, M. ; Ocké, M.C. ; Peeters, P.H.M. ; Engeset, D. ; Lund, E. ; Agudo, A. ; Larranaga, N. ; Mattisson, I. ; Andren, C. ; Johansson, I. ; Davey, G. ; Welch, A.A. ; Overvad, K. ; Tjonneland, A. ; Staveren, W.A. van; Saracci, R. ; Riboli, E. - \ 2002
Public Health Nutrition 5 (2002)6B. - ISSN 1368-9800 - p. 1125 - 1145.
dietary-intake measurements - multicenter cohort - measurement error - relative risk - questionnaire - validity - food
The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres.