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Search Result (484 REFERENCES)

2015

Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study

Chajes V., Biessy C., Ferrari P., Romieu I., Freisling H., Huybrechts I., Scalbert A., Bueno de Mesquita B., Romaguera D., Gunter M.J., Vineis P., Hansen C.P., Jakobsen M.U., Clavel-Chapelon F., Fagherazzi G., Boutron-Ruault M.C., Katzke V., Neamat-Allah J., Boeing H., Bachlechner U., Trichopoulou A., Naska A., Orfanos P., Pala V., Masala G., Mattiello A., Skeie G., Weiderpass E., Agudo A., Huerta J.M., Ardanaz E., Sanchez M.J., Dorronsoro M., Quiros J.R., Johansson I., Winkvist A., Sonested E., Key T., Khaw K.T., Wareham N.J., Peeters P.H., Slimani N.

PLoS. One; 2015; 10(2): e0118206

PMID:25675445

Abstract as provided by PubMed

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 cis-monounsaturated 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

Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition

de Batlle J., Ferrari P., Chajes V., Park J.Y., Slimani N., McKenzie F., Overvad K., Roswall N., Tjonneland A., Boutron-Ruault M.C., Clavel-Chapelon F., Fagherazzi G., Katzke V., Kaaks R., Bergmann M.M., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Sieri S., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita H.B., Peeters P.H., Hjartaker A., Engeset D., Weiderpass E., Sanchez S., Travier N., Sanchez M.J., Amiano P., Chirlaque M.D., Barricarte Gurrea A., Khaw K.T., Key T.J., Bradbury K.E., Ericson U., Sonestedt E., Van Guelpen B., Schneede J., Riboli E., Romieu I.

J Natl Cancer Inst; 2015; 107(1): 367

PMID:25505228

Abstract as provided by PubMed

BACKGROUND: There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. RESULTS: A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P trend = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P trend = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P trend = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (>12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P interaction = .035). CONCLUSIONS: Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women

Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

Duarte-Salles T., Fedirko V., Stepien M., Aleksandrova K., Bamia C., Lagiou P., Laursen A.S., Hansen L., Overvad K., Tjonneland A., Boutron-Ruault M.C., Fagherazzi G., His M., Boeing H., Katzke V., Kuhn T., Trichopoulou A., Valanou E., Kritikou M., Masala G., Panico S., Sieri S., Ricceri F., Tumino R., Bueno-de-Mesquita H.B., Peeters P.H., Hjartaker A., Skeie G., Weiderpass E., Ardanaz E., Bonet C., Chirlaque M.D., Dorronsoro M., Quiros J.R., Johansson I., Ohlsson B., Sjoberg K., Wennberg M., Khaw K.T., Travis R.C., Wareham N., Ferrari P., Freisling H., Romieu I., Cross A.J., Gunter M., Lu Y., Jenab M.

Int J Cancer; 2015; 137(11): 2715-2728

PMID:26081477

Abstract as provided by PubMed

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

Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC)

Ekelund U., Ward H.A., Norat T., Luan J., May A.M., Weiderpass E., Sharp S.J., Overvad K., Ostergaard J.N., Tjonneland A., Johnsen N.F., Mesrine S., Fournier A., Fagherazzi G., Trichopoulou A., Lagiou P., Trichopoulos D., Li K., Kaaks R., Ferrari P., Licaj I., Jenab M., Bergmann M., Boeing H., Palli D., Sieri S., Panico S., Tumino R., Vineis P., Peeters P.H., Monnikhof E., Bueno-de-Mesquita H.B., Quiros J.R., Agudo A., Sanchez M.J., Huerta J.M., Ardanaz E., Arriola L., Hedblad B., Wirfalt E., Sund M., Johansson M., Key T.J., Travis R.C., Khaw K.T., Brage S., Wareham N.J., Riboli E.

Am J Clin Nutr; 2015; 101(3): 613-621

PMID:25733647

Abstract as provided by PubMed

BACKGROUND: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. OBJECTIVE: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. DESIGN: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (>/=102 cm for men, >/=88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. RESULTS: Significant interactions (PA x BMI and PA x WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. CONCLUSION: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health

Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort

Engeset D., Braaten T., Teucher B., Kuhn T., Bueno-de-Mesquita H.B., Leenders M., Agudo A., Bergmann M.M., Valanou E., Naska A., Trichopoulou A., Key T.J., Crowe F.L., Overvad K., Sonestedt E., Mattiello A., Peeters P.H., Wennberg M., Jansson J.H., Boutron-Ruault M.C., Dossus L., Dartois L., Li K., Barricarte A., Ward H., Riboli E., Agnoli C., Huerta J.M., Sanchez M.J., Tumino R., Altzibar J.M., Vineis P., Masala G., Ferrari P., Muller D.C., Johansson M., Luisa Redondo M., Tjonneland A., Olsen A., Olsen K.S., Brustad M., Skeie G., Lund E.

Eur. J Epidemiol; 2015; 30(1): 57-70

Abstract as provided by PubMed

Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046)

A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus

Fanidi A., Relton C., Ueland P.M., Midttun O., Vollset S.E., Travis R.C., Trichopoulou A., Lagiou P., Trichopoulos D., Bueno-de-Mesquita H.B., Ros M., Boeing H., Tumino R., Panico S., Palli D., Sieri S., Vineis P., Sanchez M.J., Huerta J.M., Barricarte Gurrea A., Lujan-Barroso L., Quiros J.R., Tjonneland A., Halkjaer J., Boutron-Ruault M.C., Clavel-Chapelon F., Cadeau C., Weiderpass E., Johansson M., Riboli E., Brennan P., Johansson M.

Int J Cancer; 2015; 136(4): 915-927

PMID:24975698

Abstract as provided by PubMed

Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4 vs. Q1 ] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4 vs. Q1 0.63, 95% CI 0.35-1.16, p for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 x 10(-4) ), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck

Body iron status and gastric cancer risk in the EURGAST study

Fonseca-Nunes A., Agudo A., Aranda N., Arija V., Cross A. J., Molina E., Sanchez M. J., Bueno-de-Mesquita H. B., Siersema P., Weiderpass E., Krogh V., Mattiello A., Tumino R., Saieva C., Naccarati A., Ohlsson B., Sjoberg K., Boutron-Ruault M. C., Cadeau C., Fagherazzi G., Boeing H., Steffen A., Kuhn T., Katzke V., Tjonneland A., Olsen A., Khaw K. T., Wareham N., Key T., Lu Y., Riboli E., Peeters P. H., Gavrila D., Dorronsoro M., Quiros J. R., Barricarte A., Jenab M., Zamora-Ros R., Freisling H., Trichopoulou A., Lagiou P., Bamia C., Jakszyn P.

Int J Cancer; 2015; 137(12): 2904-14

PMID:26135329

Abstract as provided by PubMed

Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2 = 0.80, 95% CI = 0.72-0.88; OR10%increment = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 microg/dl = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort

Fortner R. T., Ose J., Merritt M. A., Schock H., Tjonneland A., Hansen L., Overvad K., Dossus L., Clavel-Chapelon F., Baglietto L., Boeing H., Trichopoulou A., Benetou V., Lagiou P., Agnoli C., Mattiello A., Masala G., Tumino R., Sacerdote C., Bueno-de-Mesquita H. B., Onland-Moret N. C., Peeters P. H., Weiderpass E., Torhild Gram I., Duell E. J., Larranaga N., Ardanaz E., Sanchez M. J., Chirlaque M. D., Brandstedt J., Idahl A., Lundin E., Khaw K. T., Wareham N., Travis R. C., Rinaldi S., Romieu I., Gunter M. J., Riboli E., Kaaks R.

Int J Cancer; 2015; 137(5): 1196-208

PMID:25656413

Abstract as provided by PubMed

Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Hughes D.J., Fedirko V., Jenab M., Schomburg L., Meplan C., Freisling H., Bueno-de-Mesquita H.B., Hybsier S., Becker N.P., Czuban M., Tjonneland A., Outzen M., Boutron-Ruault M.C., Racine A., Bastide N., Kuhn T., Kaaks R., Trichopoulos D., Trichopoulou A., Lagiou P., Panico S., Peeters P.H., Weiderpass E., Skeie G., Dagrun E., Chirlaque M.D., Sanchez M.J., Ardanaz E., Ljuslinder I., Wennberg M., Bradbury K.E., Vineis P., Naccarati A., Palli D., Boeing H., Overvad K., Dorronsoro M., Jakszyn P., Cross A.J., Quiros J.R., Stepien M., Kong S.Y., Duarte-Salles T., Riboli E., Hesketh J.E.

Int J Cancer; 2015; 136(5): 1149-1161

Abstract as provided by PubMed

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 mug/L and 4.3 mg/L in cases and 85.6 mug/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 mug/L increase). However, sub-group analyses by sex showed a statistically significant association for women (ptrend = 0.032; per 25 mug/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (ptrend = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (ptrend = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women

Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk

Jeurnink S.M., Ros M.M., Leenders M., van Duijnhoven F.J., Siersema P.D., Jansen E.H., Van Gils C.H., Bakker M.F., Overvad K., Roswall N., Tjonneland A., Boutron-Ruault M.C., Racine A., Cadeau C., Grote V., Kaaks R., Aleksandrova K., Boeing H., Trichopoulou A., Benetou V., Valanou E., Palli D., Krogh V., Vineis P., Tumino R., Mattiello A., Weiderpass E., Skeie G., Castano J.M., Duell E.J., Barricarte A., Molina-Montes E., Arguelles M., Dorronsoro M., Johansen D., Lindkvist B., Sund M., Crowe F.L., Khaw K.T., Jenab M., Fedirko V., Riboli E., Bueno-de-Mesquita H.B.

Int. J Cancer; 2015; 136(6): E665-E676

Abstract as provided by PubMed

Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (alpha- and beta-carotene, lycopene, beta-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), alpha- and gamma-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma beta-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and alpha-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For alpha- and beta-carotene, lutein, sum of carotenoids and gamma-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of beta-carotene, zeaxanthin and alpha-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted

Lag times between lymphoproliferative disorder and clinical diagnosis of chronic lymphocytic leukemia: a prospective analysis using plasma soluble CD23

Kaaks R., Sookthai D., Luczynska A., Oakes C.C., Becker S., Johnson T., Johansson A., Melin B., Sjoberg K., Trichopoulos D., Trichopoulou A., Lagiou P., Mattiello A., Tumino R., Masala G., Agnoli C., Boeing H., Aleksandrova K., Brennan P., Franceschi S., Roulland S., Casabonne D., de Sanjose S., Sanchez M.J., Huerta J.M., Ardanaz E., Sala N., Overvad K., Tjonneland A., Halkjaer J., Weiderpass E., Bueno-de-Mesquita H.B., Vermeulen R., Peeters P.H., Vineis P., Kelly R.S., Khaw K.T., Travis R.C., Key T.J., Riboli E., Nieters A.

Cancer Epidemiol. Biomarkers Prev; 2015; 24(3): 538-545

PMID:25542829

Abstract as provided by PubMed

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time. METHODS: Within the European Prospective Investigation into Cancer cohort, we measured prediagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer. RESULTS: In a very large proportion of CLL patients' plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% confidence interval (CI), 0.90-1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86-0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 0.65-0.86) for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at >45% sensitivity. CONCLUSIONS: Our findings provide unique documentation for the very long latency times during which measurable B-cell lymphoproliferative disorder exists before the clinical manifestation of CLL. IMPACT: Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag times indicate a time frame within which an early detection of CLL would be theoretically possible. Cancer Epidemiol Biomarkers Prev; 24(3); 538-45. (c)2014 AACR

Determinants of the t(14;18) translocation and their role in t(14;18)-positive follicular lymphoma

Kelly R. S., Roulland S., Morgado E., Sungalee S., Jouve N., Tumino R., Krogh V., Panico S., Polidoro S., Masala G., Sanchez M. J., Chirlaque M. D., Sala N., Gurrea A. B., Dorronsoro M., Travis R. C., Riboli E., Gunter M., Murphy N., Vermeulen R., Bueno-de-Mesquita H. B., Peeters P. H., Trichopoulou A., Trichopoulos D., Lagiou P., Nieters A., Canzian F., Kaaks R., Boeing H., Weiderpass E., Stocks T., Melin B., Overvad K., Tjonneland A., Olsen A., Brennan P., Johansson M., Nadel B., Vineis P.

Cancer Causes Control; 2015; 26(12): 1845-55

PMID:26424368

Abstract as provided by PubMed

PURPOSE: The strong association between t(14;18) translocation and follicular lymphoma (FL) is well known. However, the determinants of this chromosomal aberration and their role in t(14;18) associated FL remain to be established. METHODS: t(14;18) frequency within the B cell lymphoma 2 major breakpoint region was determined for 135 incident FL cases and 251 healthy controls as part of a nested case-control study within the European Prospective Investigation into Cancer cohort. Quantitative real-time PCR was performed in DNA extracted from blood samples taken at recruitment. The relationship between prevalence and frequency of the translocation with baseline anthropometric, lifestyle, and dietary factors in cases and controls was determined. Unconditional logistic regression was used to explore whether the risk of FL associated with these factors differed in t(14;18)(+) as compared to t(14;18)(-) cases. RESULTS: Among incident FL cases, educational level (chi (2) p = 0.021) and height (chi (2) p = 0.025) were positively associated with t(14;18) prevalence, and cases with high frequencies [t(14;18)(HF)] were significantly taller (t test p value = 0.006). These findings were not replicated in the control population, although there were a number of significant associations with dietary variables. Further analyses revealed that height was a significant risk factor for t(14;18)(+) FL [OR 6.31 (95 % CI 2.11, 18.9) in the tallest versus the shortest quartile], but not t(14;18)(-) cases. CONCLUSIONS: These findings suggest a potential role for lifestyle factors in the prevalence and frequency of the t(14;18) translocation. The observation that the etiology of FL may differ by t(14;18) status, particularly with regard to height, supports the subdivision of FL by translocation status.

Human papillomavirus antibodies and future risk of anogenital cancer: a nested case-control study in the European prospective investigation into cancer and nutrition study

Kreimer A.R., Brennan P., Lang Kuhs K.A., Waterboer T., Clifford G., Franceschi S., Michel A., Willhauck-Fleckenstein M., Riboli E., Castellsague X., Hildesheim A., Fortner R.T., Kaaks R., Palli D., Ljuslinder I., Panico S., Clavel-Chapelon F., Boutron-Ruault M.C., Mesrine S., Trichopoulou A., Lagiou P., Trichopoulos D., Peeters P.H., Cross A.J., Bueno-de-Mesquita H.B., Vineis P., Larranaga N., Pala V., Sanchez M.J., Navarro C., Barricarte A., Tumino R., Khaw K.T., Wareham N., Boeing H., Steffen A., Travis R.C., Quiros J.R., Weiderpass E., Pawlita M., Johansson M.

J Clin. Oncol; 2015; 33(8): 877-884

PMID:25667279

Abstract as provided by PubMed

PURPOSE: Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. METHODS: Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. RESULTS: HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. CONCLUSION: HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers

Pre-diagnostic polyphenol intake and breast cancer survival: the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Kyro C., Zamora-Ros R., Scalbert A., Tjonneland A., Dossus L., Johansen C., Bidstrup P. E., Weiderpass E., Christensen J., Ward H., Aune D., Riboli E., His M., Clavel-Chapelon F., Baglietto L., Katzke V., Kuhn T., Boeing H., Floegel A., Overvad K., Lasheras C., Travier N., Sanchez M. J., Amiano P., Chirlaque M. D., Ardanaz E., Khaw K. T., Wareham N., Perez-Cornago A., Trichopoulou A., Lagiou P., Vasilopoulou E., Masala G., Grioni S., Berrino F., Tumino R., Sacerdote C., Mattiello A., Bueno-de-Mesquita H. B., Peeters P. H., van Gils C., Borgquist S., Butt S., Zeleniuch-Jacquotte A., Sund M., Hjartaker A., Skeie G., Olsen A., Romieu I.

Breast Cancer Res Treat; 2015; 154(2): 389-401

PMID:26531755

Abstract as provided by PubMed

The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.

Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

Leenders M., Siersema P.D., Overvad K., Tjonneland A., Olsen A., Boutron-Ruault M.C., Bastide N., Fagherazzi G., Katzke V., Kuhn T., Boeing H., Aleksandrova K., Trichopoulou A., Lagiou P., Klinaki E., Masala G., Grioni S., Santucci de Magistris M., Tumino R., Ricceri F., Peeters P.H., Lund E., Skeie G., Weiderpass E., Quiros J.R., Agudo A., Sanchez M.J., Dorronsoro M., Navarro C., Ardanaz E., Ohlsson B., Jirstrom K., Van Guelpen B., Wennberg M., Khaw K.T., Wareham N., Key T.J., Romieu I., Huybrechts I., Cross A.J., Murphy N., Riboli E., Bueno-de-Mesquita H.B.

Int J Cancer; 2015; 137(11): 2705-2714

PMID:26077137

Abstract as provided by PubMed

Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely

An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study

Li K., Husing A., Fortner R.T., Tjonneland A., Hansen L., Dossus L., Chang-Claude J., Bergmann M., Steffen A., Bamia C., Trichopoulos D., Trichopoulou A., Palli D., Mattiello A., Agnoli C., Tumino R., Onland-Moret N.C., Peeters P.H., Bueno-de-Mesquita H.B., Gram I.T., Weiderpass E., Sanchez-Cantalejo E., Chirlaque M.D., Duell E.J., Ardanaz E., Idahl A., Lundin E., Khaw K.T., Travis R.C., Merritt M.A., Gunter M.J., Riboli E., Ferrari P., Terry K., Cramer D., Kaaks R.

Br J Cancer; 2015; 1257-1265

PMID:25742479

Abstract as provided by PubMed

BACKGROUND: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. METHODS: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study. RESULTS: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. CONCLUSION: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model

Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study

McKenzie F., Ferrari P., Freisling H., Chajes V., Rinaldi S., de Batlle J., Dahm C.C., Overvad K., Baglietto L., Dartois L., Dossus L., Lagiou P., Trichopoulos D., Trichopoulou A., Krogh V., Panico S., Tumino R., Rosso S., Bueno-de-Mesquita H.B., May A., Peeters P.H., Weiderpass E., Buckland G., Sanchez M.J., Navarro C., Ardanaz E., Andersson A., Sund M., Ericson U., Wirfalt E., Key T.J., Travis R.C., Gunter M., Riboli E., Vergnaud A.C., Romieu I.

Int. J Cancer; 2015; 136(11): 2640-2648

PMID:25379993

Abstract as provided by PubMed

Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR = 0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR = 0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR = 0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported

Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study

Merritt M. A., Riboli E., Murphy N., Kadi M., Tjonneland A., Olsen A., Overvad K., Dossus L., Dartois L., Clavel-Chapelon F., Fortner R. T., Katzke V. A., Boeing H., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Sieri S., Tumino R., Sacerdote C., Panico S., Bueno-de-Mesquita H. B., Peeters P. H., Lund E., Nakamura A., Weiderpass E., Quiros J. R., Agudo A., Molina-Montes E., Larranaga N., Dorronsoro M., Cirera L., Barricarte A., Olsson A., Butt S., Idahl A., Lundin E., Wareham N. J., Key T. J., Brennan P., Ferrari P., Wark P. A., Norat T., Cross A. J., Gunter M. J.

BMC Med; 2015; 252

PMID:26515238

Abstract as provided by PubMed

BACKGROUND: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. METHODS: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. RESULTS: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (>/=15 years versus <12; 0.90; 0.85-0.96; P for trend = 0.038). CONCLUSIONS: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.

Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII

Merritt M.A., Tzoulaki I., Tworoger S.S., De Vivo I, Hankinson S.E., Fernandes J., Tsilidis K.K., Weiderpass E., Tjonneland A., Petersen K.E., Dahm C.C., Overvad K., Dossus L., Boutron-Ruault M.C., Fagherazzi G., Fortner R.T., Kaaks R., Aleksandrova K., Boeing H., Trichopoulou A., Bamia C., Trichopoulos D., Palli D., Grioni S., Tumino R., Sacerdote C., Mattiello A., Bueno-de-Mesquita H.B., Onland-Moret N.C., Peeters P.H., Gram I.T., Skeie G., Quiros J.R., Duell E.J., Sanchez M.J., Salmeron D., Barricarte A., Chamosa S., Ericson U., Sonestedt E., Nilsson L.M., Idahl A., Khaw K.T., Wareham N., Travis R.C., Rinaldi S., Romieu I., Patel C.J., Riboli E., Gunter M.J.

Cancer Epidemiol. Biomarkers Prev; 2015; 24(2): 466-471

PMID:25662427

Abstract as provided by PubMed

Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR </= 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68-0.97, Ptrend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70-0.96, Ptrend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies. Cancer Epidemiol Biomarkers Prev; 24(2); 466-71. (c)2015 AACR

Compilation of a standardised international folate database for EPIC

Nicolas G., Witthoft C. M., Vignat J., Knaze V., Huybrechts I., Roe M., Finglas P., Slimani N.

Food Chemistry; 2015; 134-140

PMID:26433299

Abstract as provided by PubMed

This paper describes the methodology applied for compiling an "international end-user'' folate database. This work benefits from the unique dataset offered by the European Prospective Investigation into Cancer and Nutrition (EPIC) (N = 520,000 subjects in 23 centres). Compilation was done in four steps: (1) identify folate-free foods then find folate values for (2) folate-rich foods common across EPIC countries, (3) the remaining "common'' foods, and (4) "country-specific'' foods. Compiled folate values were concurrently standardised in terms of unit, mode of expression and chemical analysis, using information in national food composition tables (FCT). 43-70% total folate values were documented as measured by microbiological assay. Foods reported in EPIC were either matched directly to FCT foods, treated as recipes or weighted averages. This work has produced the first standardised folate dataset in Europe, which was used to calculate folate intakes in EPIC; a prerequisite to study the relation between folate intake and diseases. (C) 2014 Published by Elsevier Ltd.

Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk

Nimptsch K., Aleksandrova K., Boeing H., Janke J., Lee Y.A., Jenab M., Bueno-de-Mesquita H.B., Jansen E.H., Tsilidis K.K., Trichopoulou A., Weiderpass E., Wu C., Overvad K., Tjonneland A., Boutron-Ruault M.C., Dossus L., Racine A., Kaaks R., Canzian F., Lagiou P., Trichopoulos D., Palli D., Agnoli C., Tumino R., Vineis P., Panico S., Johansson A., Van Guelpen B., Khaw K.T., Wareham N., Peeters P.H., Quiros J.R., Vencesla Garcia A., Molina-Montes E., Dorronsoro M., Chirlaque M.D., Barricarte Gurrea A., Key T.J., Duarte-Salles T., Stepien M., Gunter M.J., Riboli E., Pischon T.

Int J Cancer; 2015; 136(5): 1181-1192

Abstract as provided by PubMed

High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer

Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer

Nimptsch K., Aleksandrova K., Boeing H., Janke J., Lee Y.A., Jenab M., Kong S.Y., Tsilidis K.K., Weiderpass E., Bueno-de-Mesquita H.B., Siersema P.D., Jansen E.H., Trichopoulou A., Tjonneland A., Olsen A., Wu C., Overvad K., Boutron-Ruault M.C., Racine A., Freisling H., Katzke V., Kaaks R., Lagiou P., Trichopoulos D., Severi G., Naccarati A., Mattiello A., Palli D., Grioni S., Tumino R., Peeters P.H., Ljuslinder I., Nystrom H., Brandstedt J., Sanchez M.J., Gurrea A.B., Bonet C.B., Chirlaque M.D., Dorronsoro M., Quiros J.R., Travis R.C., Khaw K.T., Wareham N., Riboli E., Gunter M.J., Pischon T.

Int. J Cancer; 2015; 137(4): 911-920

PMID:25611809

Abstract as provided by PubMed

Fetuin-A, also referred to as alpha2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 microg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 microg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development

Dietary intake of acrylamide and epithelial ovarian cancer risk in the european prospective investigation into cancer and nutrition (EPIC) cohort

Obon-Santacana M., Peeters P.H., Freisling H., Dossus L., Clavel-Chapelon F., Baglietto L., Schock H., Fortner R.T., Boeing H., Tjonneland A., Olsen A., Overvad K., Menendez V., Sanchez M.J., Larranaga N., Huerta Castano J.M., Barricarte A., Khaw K.T., Wareham N., Travis R.C., Merritt M.A., Trichopoulou A., Trichopoulos D., Orfanos P., Masala G., Sieri S., Tumino R., Vineis P., Mattiello A., Bueno-de-Mesquita H.B., Onland-Moret N.C., Wirfalt E., Stocks T., Idahl A., Lundin E., Skeie G., Gram I.T., Weiderpass E., Riboli E., Duell E.J.

Cancer Epidemiol. Biomarkers Prev; 2015; 24(1): 291-297

PMID:25300475

Abstract as provided by PubMed

Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 mug/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 mug/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10mug/d,1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed

Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort

Ose J., Fortner R.T., Schock H., Peeters P.H., Onland-Moret N.C., Bueno-de-Mesquita H.B., Weiderpass E., Gram I.T., Overvad K., Tjonneland A., Dossus L., Fournier A., Baglietto L., Trichopoulou A., Benetou V., Trichopoulos D., Boeing H., Masala G., Krogh V., Matiello A., Tumino R., Popovic M., Obon-Santacana M., Larranaga N., Ardanaz E., Sanchez M., Menendez V., Chirlaque M., Travis R.C., Khaw K., Brandstedt J., Idahl A., Lundin E., Rinaldi S., Kuhn E., Romieu I., Gunter M.J., Merritt M.A., Riboli E., Kaaks R.

Br J Cancer; 2015; 112(1): 162-166

PMID:25349976

Abstract as provided by PubMed

Background:Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics.Methods:We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n=565 cases). Multivariable conditional logistic regression models were used to estimate associations.Results:We observed no association between IGF-I and EOC overall or by tumour characteristics.Conclusions:In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk

Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

Ose J., Fortner R.T., Rinaldi S., Schock H., Overvad K., Tjonneland A., Hansen L., Dossus L., Fournier A., Baglietto L., Romieu I., Kuhn E., Boeing H., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Masala G., Sieri S., Tumino R., Sacerdote C., Mattiello A., Ramon Quiros J., Obon-Santacana M., Larranaga N., Chirlaque M.D., Sanchez M.J., Barricarte A., Peeters P.H., Bueno-de-Mesquita H.B., Onland-Moret N.C., Brandstedt J., Lundin E., Idahl A., Weiderpass E., Gram I.T., Lund E., Kaw K.T., Travis R.C., Merritt M.A., Gunther M.J., Riboli E., Kaaks R.

Int. J Cancer; 2015; 136(2): 399-410

Abstract as provided by PubMed

The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet </= 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed

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