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2015

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

PMID:25042282

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

PMID:25175624

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

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

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

PMID:25043606

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

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

Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort

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

Cancer Epidemiol. Biomarkers Prev; 2015; 24(6): 951-961

PMID:25855626

Abstract as provided by PubMed

BACKGROUND: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. RESULTS: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP </=1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist </=80: ORlog2, 0.97 (0.81-1.16); waist >88: ORlog2, 1.78 (1.28-2.48), Pheterogeneity </= 0.01]. CONCLUSIONS: Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity. IMPACT: Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. Cancer Epidemiol Biomarkers Prev; 24(6); 951-61. (c)2015 AACR

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

PMID:24890047

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

Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC)

Ricceri F., Fasanelli F., Giraudo M.T., Sieri S., Tumino R., Mattiello A., Vagliano L., Masala G., Quiros J.R., Travier N., Sanchez M.J., Larranaga N., Chirlaque M.D., Ardanaz E., Tjonneland A., Olsen A., Overvad K., Chang-Claude J., Kaaks R., Boeing H., Clavel-Chapelon F., Kvaskoff M., Dossus L., Trichopoulou A., Benetou V., Adarakis G., Bueno-de-Mesquita H.B., Peeters P.H., Sund M., Andersson A., Borgquist S., Butt S., Weiderpass E., Skeie G., Khaw K.T., Travis R.C., Rinaldi S., Romieu I., Gunter M., Kadi M., Riboli E., Vineis P., Sacerdote C.

Int. J Cancer; 2015; 137(4): 940-948

PMID:25650288

Abstract as provided by PubMed

Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer

Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition

Rohrmann S., Linseisen J., Overvad K., Lund Wurtz A.M., Roswall N., Tjonneland A., Boutron-Ruault M.C., Racine A., Bastide N., Palli D., Agnoli C., Panico S., Tumino R., Sacerdote C., Weikert S., Steffen A., Kuhn T., Li K., Khaw K.T., Wareham N.J., Bradbury K.E., Peppa E., Trichopoulou A., Trichopoulos D., Bueno-de-Mesquita H.B., Peeters P.H., Hjartaker A., Skeie G., Weiderpass E., Jakszyn P., Dorronsoro M., Barricarte A., Santiuste de Pablos C., Molina-Montes E., de la Torre R.A., Ericson U., Sonestedt E., Johansson M., Ljungberg B., Freisling H., Romieu I., Cross A.J., Vergnaud A.C., Riboli E., Boeing H.

Int J Cancer; 2015; 136(5): E423-E431

PMID:25258006

Abstract as provided by PubMed

Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 and 2000. Until December 2008, 691 RCC cases have been identified. Meat and fish consumption was assessed at baseline using country-specific dietary assessment instruments; 24-hour recalls were applied in an 8% subsample for calibration purposes. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Women with a high consumption of red meat (HR = 1.36, 95% CI 1.14-1.62; calibrated, per 50 g/day) and processed meat (HR = 1.78, 95% CI 1.05-3.03; calibrated, per 50 g/day) had a higher risk of RCC, while no association existed in men. For processed meat, the association with RCC incidence was prominent in premenopausal women and was lacking in postmenopausal women (p interaction = 0.02). Neither poultry nor fish consumption were statistically significantly associated with the risk of RCC. The results show a distinct association of red and processed meat consumption with incident RCC in women but not in men. A biological explanation for these findings remains unclear

Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study

Romaguera D., Ward H., Wark P.A., Vergnaud A.C., Peeters P.H., Van Gils C.H., Ferrari P., Fedirko V., Jenab M., Boutron-Ruault M.C., Dossus L., Dartois L., Hansen C.P., Dahm C.C., Buckland G., Sanchez M.J., Dorronsoro M., Navarro C., Barricarte A., Key T.J., Trichopoulou A., Tsironis C., Lagiou P., Masala G., Pala V., Tumino R., Vineis P., Panico S., Bueno-de-Mesquita H.B., Siersema P.D., Ohlsson B., Jirstrom K., Wennberg M., Nilsson L.M., Weiderpass E., Kuhn T., Katzke V., Khaw K.T., Wareham N.J., Tjonneland A., Boeing H., Quiros J.R., Gunter M.J., Riboli E., Norat T.

BMC Med; 2015; 13(1): 107

PMID:25948112

Abstract as provided by PubMed

BACKGROUND: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. METHODS: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models. CONCLUSIONS: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients

Alcohol intake and breast cancer in the European prospective investigation into cancer and nutrition

Romieu I., Scoccianti C., Chajes V., de Batlle J., Biessy C., Dossus L., Baglietto L., Clavel-Chapelon F., Overvad K., Olsen A., Tjonneland A., Kaaks R., Lukanova A., Boeing H., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Sieri S., Tumino R., Vineis P., Panico S., Bueno-de-Mesquita H.B., Van Gils C.H., Peeters P.H., Lund E., Skeie G., Weiderpass E., Quiros Garcia J.R., Chirlaque M.D., Ardanaz E., Sanchez M.J., Duell E.J., Amiano P., Borgquist S., Wirfalt E., Hallmans G., Johansson I., Nilsson L.M., Khaw K.T., Wareham N., Key T.J., Travis R.C., Murphy N., Wark P.A., Ferrari P., Riboli E.

Int. J Cancer; 2015; 137(8): 1921-1930

PMID:25677034

Abstract as provided by PubMed

Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7-5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-,

Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: results from the EPIC cohort study

Sanikini H., Dik V.K., Siersema P.D., Bhoo-Pathy N., Uiterwaal C.S., Peeters P.H., Gonzalez C.A., Zamora-Ros R., Overvad K., Tjonneland A., Roswall N., Boutron-Ruault M.C., Fagherazzi G., Racine A., Kuhn T., Katzke V., Boeing H., Trichopoulou A., Trichopoulos D., Lagiou P., Palli D., Grioni S., Vineis P., Tumino R., Panico S., Weiderpass E., Skeie G., Braaten T., Huerta J.M., Sanchez-Cantalejo E., Barricarte A., Sonestedt E., Wallstrom P., Nilsson L.M., Johansson I., Bradbury K.E., Khaw K.T., Wareham N., Huybrechts I., Freisling H., Cross A.J., Riboli E., Bueno-de-Mesquita H.B.

Int. J. Cancer; 2015; 136(6): E720-E730

PMID:25236393

Abstract as provided by PubMed

Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-confidence intervals [CI]: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, p-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding

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