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2014

Prediagnostic immunoglobulin E levels and risk of chronic lymphocytic leukemia, other lymphomas and multiple myeloma-results of the European Prospective Investigation into Cancer and Nutrition

Nieters A., Luczynska A., Becker S., Becker N., Vermeulen R., Overvad K., Aleksandrova K., Boeing H., Lagiou P., Trichopoulos D., Trichopoulou A., Krogh V., Masala G., Panico S., Tumino R., Sacerdote C., Bueno-de-Mesquita B., Jeurnink S.M., Weiderpass E., Ardanaz E., Chirlaque M.D., Sanchez M.J., Sanchez S., Borgquist S., Butt S., Melin B., Spath F., Rinaldi S., Brennan P., Kelly R.S., Riboli E., Vineis P., Kaaks R.

Carcinogenesis; 2014; 35(12): 2716-2722

PMID:25269801

Abstract as provided by PubMed

Previous epidemiological studies suggest an inverse association between allergies, marked by elevated immunoglobulin (Ig) E levels, and non-Hodgkin lymphoma (NHL) risk. The evidence, however, is inconsistent and prospective data are sparse. We examined the association between prediagnostic total (low: <20; intermediate: 20-100; high >100 kU/l) and specific IgE (negative: <0.35; positive >/=0.35 kU/I) concentrations against inhalant antigens and lymphoma risk in a study nested within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 1021 incident cases and matched controls of NHL, multiple myeloma (MM) and Hodgkin lymphoma with a mean follow-up time of 7 years were investigated. Multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CI) were calculated by conditional logistic regression. Specific IgE was not associated with the risk of MM, B-cell NHL and B-cell NHL subtypes. In contrast, total IgE levels were inversely associated with the risk of MM [high level: OR = 0.40 (95% CI = 0.21-0.79)] and B-cell NHL [intermediate level: OR = 0.68 (95% CI = 0.53-0.88); high level: OR = 0.62 (95% CI = 0.44-0.86)], largely on the basis of a strong inverse association with chronic lymphocytic leukemia [CLL; intermediate level: OR = 0.49 (95% CI = 0.30-0.80); high level: OR = 0.13 (95% CI = 0.05-0.35)] risk. The inverse relationship for CLL remained significant for those diagnosed 5 years after baseline. The findings of this large prospective study demonstrated significantly lower prediagnostic total IgE levels among CLL and MM cases compared with matched controls. This corresponds to the clinical immunodeficiency state often observed in CLL patients prior to diagnosis. No support for an inverse association between prediagnostic levels of specific IgE and NHL risk was found

Plasma methionine, choline, betaine, and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Nitter M., Norgard B., de Vogel S., Eussen S.J., Meyer K., Ulvik A., Ueland P.M., Nygard O., Vollset S.E., Bjorge T., Tjonneland A., Hansen L., Boutron-Ruault M., Racine A., Cottet V., Kaaks R., Kuhn T., Trichopoulou A., Bamia C., Naska A., Grioni S., Palli D., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita H.B., van Kranen H., Peeters P.H., Weiderpass E., Dorronsoro M., Jakszyn P., Sanchez M., Arguelles M., Huerta J.M., Barricarte A., Johansson M., Ljuslinder I., Khaw K., Wareham N., Freisling H., Duarte-Salles T., Stepien M., Gunter M.J., Riboli E.

Ann Oncol; 2014; 25(8): 1609-1615

PMID:24827130

Abstract as provided by PubMed

BACKGROUND: Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low. PATIENTS AND METHODS: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations. RESULTS: Overall, methionine (OR: 0.79, 95% CI: 0.63-0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60-0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66-1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50-1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43-0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk. CONCLUSIONS: Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Obon-Santacana M., Kaaks R., Slimani N., Lujan-Barroso L., Freisling H., Ferrari P., Dossus L., Chabbert-Buffet N., Baglietto L., Fortner R.T., Boeing H., Tjonneland A., Olsen A., Overvad K., Menendez V., Molina-Montes E., Larranaga N., Chirlaque M.D., Ardanaz E., Khaw K.T., Wareham N., Travis R.C., Lu Y., Merritt M.A., Trichopoulou A., Benetou V., Trichopoulos D., Saieva C., Sieri S., Tumino R., Sacerdote C., Galasso R., Bueno-de-Mesquita H.B., Wirfalt E., Ericson U., Idahl A., Ohlson N., Skeie G., Gram I.T., Weiderpass E., Onland-Moret N.C., Riboli E., Duell E.J.

Br J Cancer; 2014; 111(5): 987-997

PMID:24937665

Abstract as provided by PubMed

BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort

Rinaldi S., Kaaks R., Friedenreich C.M., Key T.J., Travis R., Biessy C., Slimani N., Overvad K., Ostergaard J.N., Tjonneland A., Olsen A., Mesrine S., Fournier A., Dossus L., Lukanova A., Johnson T., Boeing H., Vigl M., Trichopoulou A., Benetou V., Trichopoulos D., Masala G., Krogh V., Tumino R., Ricceri F., Panico S., Bueno-de-Mesquita H.B., Monninkhof E.M., May A.M., Weiderpass E., Quiros J.R., Travier N., Molina-Montes E., Amiano P., Huerta J.M., Ardanaz E., Sund M., Johansson M., Khaw K.T., Wareham N., Scalbert A., Gunter M.J., Riboli E., Romieu I.

Cancer Causes Control; 2014; 25(1): 111-124

PMID:24173534

Abstract as provided by PubMed

PURPOSE: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. METHODS: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. RESULTS: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was <2 %. CONCLUSIONS: Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size

Anthropometric measures and bladder cancer risk: A prospective study in the EPIC cohort

Roswall N., Freisling H., Bueno-de-Mesquita H.B., Ros M., Christensen J., Overvad K., Boutron-Ruault M.C., Severi G., Fagherazzi G., Chang-Claude J., Kaaks R., Steffen A., Boeing H., Arguelles M., Agudo A., Sanchez M.J., Chirlaque M.D., Barricarte Gurrea A., Amiano P., Wareham N., Khaw K.T., Bradbury K.E., Trichopoulou A., Papatesta H.M., Trichopoulos D., Palli D., Pala V., Tumino R., Sacerdote C., Mattiello A., Peeters P.H., Ehrnstrom R., Brennan P., Ferrari P., Ljungberg B., Norat T., Gunter M., Riboli E., Weiderpass E., Halkjaer J.

Int J Cancer; 2014; 135(12): 2918-2929

PMID:24771290

Abstract as provided by PubMed

Anthropometric measures have been related to risk of several cancers. For bladder cancer, however, evidence is sparse. Comparability of existing studies is hampered by use of different obesity-measures, inadequate control for smoking, and few female cases. This study examined associations between height, weight, waist and hip circumference, waist-hip ratio, waist-height ratio, body mass index (BMI), recalled weight at age 20 and bladder cancer, and investigated effect modification by age, tumor aggressiveness and smoking. The study was conducted in the European Prospective Investigation into Cancer and Nutrition cohort, in 390,878 participants. Associations were calculated using Cox Proportional Hazards Models. During follow-up, 1,391 bladder cancers (1,018 male; 373 female) occurred. Height was unrelated to bladder cancer in both genders. We found a small but significant positive association with weight [1.04 (1.01-1.07) per 5 kilo], BMI [1.05 (1.02-1.08) per 2 units], waist circumference [1.04 (1.01-1.08) per 5 cm], waist-hip ratio (1.07 (1.02-1.13) per 0.05 unit] and waist-height ratio [1.07 (1.01-1.13) per 0.05 unit] in men. Stratification by smoking status confined associations in men to former smokers. In never smokers, we found no significant associations, suggesting residual confounding by smoking. Results did not differ with tumor aggressiveness and age. Residual analyses on BMI/waist circumference showed a significantly higher disease risk with BMI in men (p = 0.01), but no association with waist circumference. In conclusion, in this large study, height was unrelated to bladder cancer, whereas overweight was associated with a slightly higher bladder cancer risk in men. This association may, however, be distorted by residual confounding by smoking

t(14;18) Translocation: A Predictive Blood Biomarker for Follicular Lymphoma

Roulland S., Kelly R.S., Morgado E., Sungalee S., Solal-Celigny P., Colombat P., Jouve N., Palli D., Pala V., Tumino R., Panico S., Sacerdote C., Quiros J.R., Gonzales C.A., Sanchez M.J., Dorronsoro M., Navarro C., Barricarte A., Tjonneland A., Olsen A., Overvad K., Canzian F., Kaaks R., Boeing H., Drogan D., Nieters A., Clavel-Chapelon F., Trichopoulou A., Trichopoulos D., Lagiou P., Bueno-de-Mesquita H.B., Peeters P.H., Vermeulen R., Hallmans G., Melin B., Borgquist S., Carlson J., Lund E., Weiderpass E., Khaw K.T., Wareham N., Key T.J., Travis R.C., Ferrari P., Romieu I., Riboli E., Salles G., Vineis P., Nadel B.

J Clin Oncol; 2014; 32(13): 1347-1355

PMID:24687831

Abstract as provided by PubMed

PURPOSE: The (14;18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t(14;18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t(14;18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL. PARTICIPANTS AND METHODS: Among 520,000 healthy participants enrolled onto the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort, we identified 100 who developed FL 2 to 161 months after enrollment. Prediagnostic blood from these and 218 controls were screened for t(14;18) using sensitive polymerase chain reaction-based assays. Results were subsequently validated in an independent cohort (65 case participants; 128 controls). Clonal relationships between t(14;18) cells and FL were also assessed by molecular backtracking of paired prediagnostic blood and tumor samples. RESULTS: Clonal analysis of t(14;18) junctions in paired prediagnostic blood versus tumor samples demonstrated that progression to FL occurred from t(14;18)-positive committed precursors. Furthermore, healthy participants at enrollment who developed FL up to 15 years later showed a markedly higher t(14;18) prevalence and frequency than controls (P < .001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency > 10(-4) (odds ratio, 23.17; 95% CI, 9.98 to 67.31; P < .001). Remarkably, risk estimates remained high and significant up to 15 years before diagnosis. CONCLUSION: High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for FL, effective years before diagnosis

Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort

Roura E., Castellsague X., Pawlita M., Travier N., Waterboer T., Margall N., Bosch F.X., de Sanjose S., Dillner J., Gram I.T., Tjonneland A., Munk C., Pala V., Palli D., Khaw K.T., Barnabas R.V., Overvad K., Clavel-Chapelon F., Boutron-Ruault M.C., Fagherazzi G., Kaaks R., Lukanova A., Steffen A., Trichopoulou A., Trichopoulos D., Klinaki E., Tumino R., Sacerdote C., Panico S., Bueno-de-Mesquita H.B., Peeters P.H., Lund E., Weiderpass E., Redondo M.L., Sanchez M.J., Tormo M.J., Barricarte A., Larranaga N., Ekstrom J., Hortlund M., Lindquist D., Wareham N., Travis R.C., Rinaldi S., Tommasino M., Franceschi S., Riboli E.

Int J Cancer; 2014; 135(2): 453-466

PMID:24338632

Abstract as provided by PubMed

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation

Dietary Intakes and Risk of Lymphoid and Myeloid Leukemia in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Saberi Hosnijeh F., Peeters P., Romieu I., Kelly R., Riboli E., Olsen A., Tjonneland A., Fagherazzi G., Clavel-Chapelon F., Dossus L., Nieters A., Teucher B., Trichopoulou A., Naska A., Valanou E., Mattiello A., Sieri S., Parr C.L., Engeset D., Skeie G., Dorronsoro M., Barricarte A., Sanchez M.J., Ericson U., Sonestedt E., Bueno-de-Mesquita H.B., Ros M.M., Travis R.C., Key T.J., Vineis P., Vermeulen R.

Nutr. Cancer; 2014; 66(1): 14-28

PMID:24279598

Abstract as provided by PubMed

The etiology of leukemias cannot entirely be explained by known risk factors, including ionizing radiation, benzene exposure, and infection with human T cell leukemia virus. A number of studies suggested that diet influences the risk of adult leukemias. However, results have been largely inconsistent. We examined the potential association between dietary factors and risk of leukemias among participants of the European Prospective Investigation into Cancer and Nutrition study. Among the 477,325 participants with mean follow-up of 11.34 yr (SD = 2.47), 773 leukemias (373 and 342 cases of lymphoid and myeloid leukemia, respectively) were identified. Diet over the previous 12 mo was assessed at baseline using a validated country-specific dietary questionnaire. Cox proportional hazards regression was used to explore the association between dietary factors that have previously been associated with leukemia risk, including red and processed meat, poultry, offal, fish, dairy products, vegetables, fruits, and seeds/nuts, and risk of both lymphoid and myeloid leukemias. No significant associations were observed between dietary measures and total, lymphoid, and myeloid leukemias. Additional subtype analyses showed no dietary association with risk of major subtypes of leukemias. In summary, this study did not support a possible link between selected dietary factors and risk of leukemias

Insulin-like growth factor-i and risk of differentiated thyroid carcinoma in the European prospective investigation into cancer and nutrition

Schmidt J.A., Allen N.E., Almquist M., Franceschi S., Rinaldi S., Tipper S.J., Tsilidis K.K., Weiderpass E., Overvad K., Tjonneland A., Boutron-Ruault M.C., Dossus L., Mesrine S., Kaaks R., Lukanova A., Boeing H., Lagiou P., Trichopoulos D., Trichopoulou A., Palli D., Krogh V., Panico S., Tumino R., Zanetti R., Bueno-de-Mesquita H.B., Peeters P.H., Lund E., Menendez V., Agudo A., Sanchez M.J., Chirlaque M.D., Ardanaz E., Larranaga N., Hennings J., Sandstrom M., Khaw K.T., Wareham N., Romieu I., Gunter M.J., Riboli E., Key T.J., Travis R.C.

Cancer Epidemiol Biomarkers Prev; 2014; 23(6): 976-985

PMID:24646451

Abstract as provided by PubMed

BACKGROUND: Little is known about the causes of thyroid cancer, but insulin-like growth factor-I (IGF-I) might play an important role in its development due to its mitogenic and antiapoptotic properties. METHODS: This study prospectively investigated the association between serum IGF-I concentrations and risk of differentiated thyroid carcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. The 345 incident cases of differentiated thyroid carcinoma were individually matched to 735 controls by study center, sex and age, date, time, and fasting status at blood collection, follow-up duration, and for women menopausal status, use of exogenous hormones, and phase of menstrual cycle at blood collection. Serum IGF-I concentrations were measured by immunoassay, and risk of differentiated thyroid cancer in relation to IGF-I concentration was estimated using conditional logistic regression. RESULTS: There was a positive association between IGF-I concentrations and risk of differentiated thyroid carcinoma: the OR for a doubling in IGF-I concentration was 1.48 (95% confidence interval, 1.06-2.08; Ptrend = 0.02). The positive association with IGF-I was stable over time between blood collection and cancer diagnosis. CONCLUSION: These findings suggest that IGF-I concentrations may be positively associated with risk of differentiated thyroid carcinoma. IMPACT: This study provides the first prospective evidence of a potential association between circulating IGF-I concentrations and risk of differentiated thyroid carcinoma and may prompt the further investigations needed to confirm the association

Smoking and Long-Term Risk of Type 2 Diabetes: The EPIC-InterAct Study in European Populations

Spijkerman A.M., van der A.DL, Nilsson P.M., Ardanaz E., Gavrila D., Agudo A., Arriola L., Balkau B., Beulens J.W., Boeing H., de Lauzon-Guillain B., Fagherazzi G., Feskens E.J., Franks P.W., Grioni S., Huerta J.M., Kaaks R., Key T.J., Overvad K., Palli D., Panico S., Redondo M.L., Rolandsson O., Roswall N., Sacerdote C., Sanchez M.J., Schulze M.B., Slimani N., Teucher B., Tjonneland A., Tumino R., van der Schouw Y.T., Langenberg C., Sharp S.J., Forouhi N.G., Riboli E., Wareham N.J.

Diabetes Care; 2014; 37(12): 3164-3171

PMID:25336749

Abstract as provided by PubMed

OBJECTIVE: The aims of this study were to investigate the association between smoking and incident type 2 diabetes, accounting for a large number of potential confounding factors, and to explore potential effect modifiers and intermediate factors. RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct is a prospective case-cohort study within eight European countries, including 12,403 cases of incident type 2 diabetes and a random subcohort of 16,835 individuals. After exclusion of individuals with missing data, the analyses included 10,327 cases and 13,863 subcohort individuals. Smoking status was used (never, former, current), with never smokers as the reference. Country-specific Prentice-weighted Cox regression models and random-effects meta-analysis were used to estimate hazard ratios (HRs) for type 2 diabetes. RESULTS: In men, the HRs (95% CI) of type 2 diabetes were 1.40 (1.26, 1.55) for former smokers and 1.43 (1.27, 1.61) for current smokers, independent of age, education, center, physical activity, and alcohol, coffee, and meat consumption. In women, associations were weaker, with HRs (95% CI) of 1.18 (1.07, 1.30) and 1.13 (1.03, 1.25) for former and current smokers, respectively. There was some evidence of effect modification by BMI. The association tended to be slightly stronger in normal weight men compared with those with overall adiposity. CONCLUSIONS: Former and current smoking was associated with a higher risk of incident type 2 diabetes compared with never smoking in men and women, independent of educational level, physical activity, alcohol consumption, and diet. Smoking may be regarded as a modifiable risk factor for type 2 diabetes, and smoking cessation should be encouraged for diabetes prevention

Weight change later in life and colon and rectal cancer risk in participants in the EPIC-PANACEA study

Steins Bisschop C.N., Van Gils C.H., Emaus M.J., Bueno-de-Mesquita H.B., Monninkhof E.M., Boeing H., Aleksandrova K., Jenab M., Norat T., Riboli E., Boutron-Rualt M.C., Fagherazzi G., Racine A., Palli D., Krogh V., Tumino R., Naccarati A., Mattiello A., Arguelles M.V., Sanchez M.J., Tormo M.J., Ardanaz E., Dorronsoro M., Bonet C., Khaw K.T., Key T., Trichopoulou A., Orfanos P., Naska A., Kaaks R.R., Lukanova A., Pischon T., Ljuslinder I., Jirstrom K., Ohlsson B., Overvad K., Landsvig Berentzen T., Halkjaer J., Tjonneland A., Weiderpass E., Skeie G., Braaten T., Siersema P.D., Freisling H., Ferrari P., Peeters P.H., May A.M.

Am. J Clin Nutr; 2014; 99(1): 139-147

PMID:24225355

Abstract as provided by PubMed

BACKGROUND: A moderate association exists between body mass index (BMI) and colorectal cancer. Less is known about the effect of weight change. OBJECTIVE: We investigated the relation between BMI and weight change and subsequent colon and rectal cancer risk. DESIGN: This was studied among 328,781 participants in the prospective European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating study (mean age: 50 y). Body weight was assessed at recruitment and on average 5 y later. Self-reported weight change (kg/y) was categorized in sex-specific quintiles, with quintiles 2 and 3 combined as the reference category (men: -0.6 to 0.3 kg/y; women: -0.4 to 0.4 kg/y). In the subsequent years, participants were followed for the occurrence of colon and rectal cancer (median period: 6.8 y). Multivariable Cox proportional hazards regression analyses were used to study the association. RESULTS: A total of 1261 incident colon cancer and 747 rectal cancer cases were identified. BMI at recruitment was statistically significantly associated with colon cancer risk in men (HR: 1.04; 95% CI: 1.02, 1.07). Moderate weight gain (quintile 4) in men increased risk further (HR: 1.32; 95% CI: 1.04, 1.68), but this relation did not show a clear trend. In women, BMI or weight gain was not related to subsequent risk of colon cancer. No statistically significant associations for weight loss and colon cancer or for BMI and weight changes and rectal cancer were found. CONCLUSIONS: BMI attained at adulthood was associated with colon cancer risk. Subsequent weight gain or loss was not related to colon or rectal cancer risk in men or women

Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The EPIC-InterAct Case-Cohort Study

van Nielen M., Feskens E.J., Mensink M., Sluijs I., Molina E., Amiano P., Ardanaz E., Balkau B., Beulens J.W., Boeing H., Clavel-Chapelon F., Fagherazzi G., Franks P.W., Halkjaer J., Huerta J.M., Katzke V., Key T.J., Khaw K.T., Krogh V., Kuhn T., Menendez V.V., Nilsson P., Overvad K., Palli D., Panico S., Rolandsson O., Romieu I., Sacerdote C., Sanchez M.J., Schulze M.B., Spijkerman A.M., Tjonneland A., Tumino R., van der A.DL, Wurtz A.M., Zamora-Ros R., Langenberg C., Sharp S.J., Forouhi N.G., Riboli E., Wareham N.J.

Diabetes Care; 2014; 37(7): 1854-1862

PMID:24722499

Abstract as provided by PubMed

OBJECTIVE: The long-term association between dietary protein and type 2 diabetes incidence is uncertain. We aimed to investigate the association between total, animal, and plant protein intake and the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from eight European countries, with an average follow-up time of 12.0 years. Pooled country-specific hazard ratios (HRs) and 95% CI of prentice-weighted Cox regression analyses were used to estimate type 2 diabetes incidence according to protein intake. RESULTS: After adjustment for important diabetes risk factors and dietary factors, the incidence of type 2 diabetes was higher in those with high intake of total protein (per 10 g: HR 1.06 [95% CI 1.02-1.09], Ptrend < 0.001) and animal protein (per 10 g: 1.05 [1.02-1.08], Ptrend = 0.001). Effect modification by sex (P < 0.001) and BMI among women (P < 0.001) was observed. Compared with the overall analyses, associations were stronger in women, more specifically obese women with a BMI >30 kg/m(2) (per 10 g animal protein: 1.19 [1.09-1.32]), and nonsignificant in men. Plant protein intake was not associated with type 2 diabetes (per 10 g: 1.04 [0.93-1.16], Ptrend = 0.098). CONCLUSIONS: High total and animal protein intake was associated with a modest elevated risk of type 2 diabetes in a large cohort of European adults. In view of the rapidly increasing prevalence of type 2 diabetes, limiting iso-energetic diets high in dietary proteins, particularly from animal sources, should be considered

Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations

Zamora-Ros R., Forouhi N.G., Sharp S.J., Gonzalez C.A., Buijsse B., Guevara M., van der Schouw Y.T., Amiano P., Boeing H., Bredsdorff L., Fagherazzi G., Feskens E.J., Franks P.W., Grioni S., Katzke V., Key T.J., Khaw K.T., Kuhn T., Masala G., Mattiello A., Molina-Montes E., Nilsson P.M., Overvad K., Perquier F., Redondo M.L., Ricceri F., Rolandsson O., Romieu I., Roswall N., Scalbert A., Schulze M., Slimani N., Spijkerman A.M., Tjonneland A., Tormo M.J., Touillaud M., Tumino R., van der A.DL, van Woudenbergh G.J., Langenberg C., Riboli E., Wareham N.J.

J Nutr; 2014; 144(3): 335-343

PMID:24368432

Abstract as provided by PubMed

Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile: 0.81; 95% CI: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% CI: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% CI: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D

Tea and coffee consumption and risk of esophageal cancer: The European prospective investigation into cancer and nutrition study

Zamora-Ros R., Lujan-Barroso L., Bueno-de-Mesquita H.B., Dik V.K., Boeing H., Steffen A., Tjonneland A., Olsen A., Bech B.H., Overvad K., Boutron-Ruault M.C., Racine A., Fagherazzi G., Kuhn T., Katzke V., Trichopoulou A., Lagiou P., Trichopoulos D., Tumino R., Panico S., Vineis P., Grioni S., Palli D., Weiderpass E., Skeie G., Huerta J.M., Sanchez M.J., Arguelles M., Amiano P., Ardanaz E., Nilsson L., Wallner B., Lindkvist B., Wallstrom P., Peeters P.H., Key T.J., Khaw K.T., Wareham N.J., Freisling H., Stepien M., Ferrari P., Gunter M.J., Murphy N., Riboli E., Gonzalez C.A.

Int J Cancer; 2014; 135(6): 1470-1479

PMID:24535727

Abstract as provided by PubMed

Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition. Tea and coffee intakes were recorded using country-specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow-up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20-0.88; p-trend = 0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23-0.93; p-trend = 0.053) and coffee consumption (HR 0.37, 95% CI 0.19-0.73; p-trend = 0.011). However, no statistically significant findings were observed using the continuous variable (per 100 mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases

Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Zamora-Ros R., Sacerdote C., Ricceri F., Weiderpass E., Roswall N., Buckland G., St-Jules D.E., Overvad K., Kyro C., Fagherazzi G., Kvaskoff M., Severi G., Chang-Claude J., Kaaks R., Nothlings U., Trichopoulou A., Naska A., Trichopoulos D., Palli D., Grioni S., Mattiello A., Tumino R., Gram I.T., Engeset D., Huerta J.M., Molina-Montes E., Arguelles M., Amiano P., Ardanaz E., Ericson U., Lindkvist B., Nilsson L.M., Kiemeney L.A., Ros M., Bueno-de-Mesquita H.B., Peeters P.H., Khaw K.T., Wareham N.J., Knaze V., Romieu I., Scalbert A., Brennan P., Wark P., Vineis P., Riboli E., Gonzalez C.A.

Br J Cancer; 2014; 111(9): 1870-1880

PMID:25121955

Abstract as provided by PubMed

BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC

2013

Dietary intake of vitamin D and calcium and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition

Abbas S., Linseisen J., Rohrmann S., Chang-Claude J., Peeters P.H., Engel P., Brustad M., Lund E., Skeie G., Olsen A., Tjonneland A., Overvad K., Boutron-Ruault M.C., Clavel-Chapelon F., Fagherazzi G., Kaaks R., Boeing H., Buijsse B., Adarakis G., Ouranos V., Trichopoulou A., Masala G., Krogh V., Mattiello A., Tumino R., Sacerdote C., Buckland G., Suarez M.V., Sanchez M.J., Chirlaque M.D., Barricarte A., Amiano P., Manjer J., Wirfalt E., Lenner P., Sund M., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Khaw K.T., Wareham N., Key T.J., Fedirko V., Romieu I., Gallo V., Norat T., Wark P.A., Riboli E.

Nutr. Cancer; 2013; 65(2): 178-187

PMID:23441605

Abstract as provided by PubMed

Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. During a mean follow-up of 8.8 yr, 7760 incident invasive breast cancer cases were identified among 319,985 women. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for pre- and postmenopausal breast cancer risk. Comparing the highest with the lowest quintile of vitamin D intake, HR and 95% CI were 1.07 (0.87-1.32) and 1.02 (0.90-1.16) for pre- and postmenopausal women, respectively. The corresponding HR and 95% CIs for calcium intake were 0.98 (0.80-1.19) and 0.90 (0.79-1.02), respectively. For calcium intake in postmenopausal women, the test for trend was borderline statistically significant (P(trend) = 0.05). There was no significant interaction between vitamin D and calcium intake and cancer risk (P(interaction) = 0.57 and 0.22 in pre- and postmenopausal women, respectively). In this large prospective cohort, we found no evidence for an association between dietary vitamin D or calcium intake and breast cancer risk

Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Agudo A., Bonet C., Sala N., Munoz X., Aranda N., Fonseca-Nunes A., Clavel-Chapelon F., Boutron-Ruault M.C., Vineis P., Panico S., Palli D., Tumino R., Grioni S., Quiros J.R., Molina E., Navarro C., Barricarte A., Chamosa S., Allen N.E., Khaw K.T., Bueno-de-Mesquita H.B., Siersema P.D., Numans M.E., Trichopoulou A., Lagiou P., Trichopoulos D., Kaaks R., Canzian F., Boeing H., Meidtner K., Johansson M., Sund M., Manjer J., Overvad K., Tjonneland A., Lund E., Weiderpass E., Jenab M., Fedirko V., Offerhaus G.J., Riboli E., Gonzalez C.A., Jakszyn P.

Carcinogenesis; 2013; 34(6): 1244-1250

PMID:23389292

Abstract as provided by PubMed

Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out

Adult weight change and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

Aleksandrova K., Pischon T., Buijsse B., May A.M., Peeters P.H., Bueno-de-Mesquita H.B., Jenab M., Fedirko V., Dahm C.C., Siersema P.D., Freisling H., Ferrari P., Overvad K., Tjonneland A., Trichopoulou A., Lagiou P., Naska A., Pala V., Mattiello A., Ohlsson B., Jirstrom K., Key T.J., Khaw K.T., Riboli E., Boeing H.

Eur. J Cancer; 2013; 49(16): 3526-3536

PMID:23867126

Abstract as provided by PubMed

AIM: Weight change during adult life may reflect metabolic changes and influence colorectal cancer (CRC) development, but such role is not well established. We aimed to explore the association between adult weight change (from age 20 to 50) and CRC risk. In particular, we investigated differences according to colon and rectal cancer, sex and measures of attained adiposity. METHODS: We included 201,696 participants from six participating countries in the European Prospective Investigation into Cancer and Nutrition (1992-2010). During a mean follow-up of 11.2 years 2384 (1194 in men and 1190 in women) incident CRC cases occurred. Cox proportional hazard models adjusted for body mass index at age 20 and lifestyle factors at study recruitment were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After multivariable adjustment, each kg of weight gained annually from age 20 to 50 was associated with a 60% higher risk of colon cancer (95% CI 1.20-2.09), but not rectal cancer (HR 1.13, 95% CI 0.79-1.62, P(interaction)=0.04). The higher risk of colon cancer was restricted to people with high attained waist circumference at age 50 (HR 1.82, 95%CI 1.14-2.91, P(interaction)=0.02). Results were not different in men and women (P(interaction)=0.81). CONCLUSION(S): Adult weight gain, as reflected by attained abdominal obesity at age 50, increases colon cancer risk in both men and women. These data underline the importance of weight management and metabolic health maintenance in early adult life years for colon cancer prevention

Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition

Allen N.E., Appleby P.N., Key T.J., Bueno-de-Mesquita H.B., Ros M.M., Kiemeney L.A., Tjonneland A., Roswall N., Overvad K., Weikert S., Boeing H., Chang-Claude J., Teucher B., Panico S., Sacerdote C., Tumino R., Palli D., Sieri S., Peeters P., Quiros J.R., Jakszyn P., Molina-Montes E., Chirlaque M.D., Ardanaz E., Dorronsoro M., Khaw K.T., Wareham N., Ljungberg B., Hallmans G., Ehrnstrom R., Ericson U., Gram I.T., Parr C.L., Trichopoulou A., Karapetyan T., Dilis V., Clavel-Chapelon F., Boutron-Ruault M.C., Fagherrazzi G., Romieu I., Gunter M.J., Riboli E.

Int J Cancer; 2013; 132(3): 635-644

PMID:22618737

Abstract as provided by PubMed

Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed

A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk

Baltar V.T., Xun W.W., Johansson M., Ferrari P., Chuang S.C., Relton C., Ueland P.M., Midttun O., Slimani N., Jenab M., Clavel-Chapelon F., Boutron-Ruault M.C., Fagherazzi G., Kaaks R., Rohrmann S., Boeing H., Weikert C., Bueno-de-Mesquita B., Boshuizen H., Van Gils C.H., Onland-Moret N.C., Agudo A., Barricarte A., Navarro C., Rodriguez L., Castano J.M., Larranaga N., Khaw K.T., Wareham N., Allen N.E., Crowe F., Gallo V., Norat T., Krogh V., Masala G., Panico S., Sacerdote C., Tumino R., Trichopoulou A., Lagiou P., Trichopoulos D., Rasmuson T., Hallmans G., Roswall N., Tjonneland A., Riboli E., Brennan P., Vineis P.

Eur. J Epidemiol; 2013; 28(8): 677-688

PMID:23532743

Abstract as provided by PubMed

The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms

Mediterranean diet and colorectal cancer risk: results from a European cohort

Bamia C., Lagiou P., Buckland G., Grioni S., Agnoli C., Taylor A.J., Dahm C.C., Overvad K., Olsen A., Tjonneland A., Cottet V., Boutron-Ruault M.C., Morois S., Grote V., Teucher B., Boeing H., Buijsse B., Trichopoulos D., Adarakis G., Tumino R., Naccarati A., Panico S., Palli D., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Peeters P.H., Engeset D., Skeie G., Lund E., Sanchez M.J., Barricarte A., Huerta J.M., Quiros J.R., Dorronsoro M., Ljuslinder I., Palmqvist R., Drake I., Key T.J., Khaw K.T., Wareham N., Romieu I., Fedirko V., Jenab M., Romaguera D., Norat T., Trichopoulou A.

Eur. J Epidemiol; 2013; 28(4): 317-328

PMID:23579425

Abstract as provided by PubMed

The authors investigated the association of adherence to Mediterranean diet with colorectal cancer (CRC) risk in the European Prospective Investigation into Cancer and nutrition study. Adherence to Mediterranean diet was expressed through two 10-unit scales, the Modified Mediterranean diet score (MMDS) and the Centre-Specific MMDS (CSMMDS). Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales. Adjusted hazard ratios (HR) for the associations of these scales with CRC incidence were estimated. After 5,296,617 person-years of follow-up, 4,355 incident CRC cases were identified. A decreased risk of CRC, of 8 and 11 % was estimated when comparing the highest (scores 6-9) with the lowest (scores 0-3) adherence to CSMMDS and MMDS respectively. For MMDS the HR was 0.89 (95 % confidence interval (CI): 0.80, 0.99). A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk (HR for MMDS: 0.96; 95 % CI: 0.92, 1.00). These associations were somewhat more evident, among women, were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS. These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk

The association of pattern of lifetime alcohol use and cause of death in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Bergmann M.M., Rehm J., Klipstein-Grobusch K., Boeing H., Schutze M., Drogan D., Overvad K., Tjonneland A., Halkjaer J., Fagherazzi G., Boutron-Ruault M.C., Clavel-Chapelon F., Teucher B., Kaaks R., Trichopoulou A., Benetou V., Trichopoulos D., Palli D., Pala V., Tumino R., Vineis P., Beulens J.W., Redondo M.L., Duell E.J., Molina-Montes E., Navarro C., Barricarte A., Arriola L., Allen N.E., Crowe F.L., Khaw K.T., Wareham N., Romaguera D., Wark P.A., Romieu I., Nunes L., Riboli E., Ferrari P.

Int. J Epidemiol; 2013; 42(6): 1772-1790

PMID:24415611

Abstract as provided by PubMed

BACKGROUND: There is limited evidence for an association between the pattern of lifetime alcohol use and cause-specific risk of death. METHODS: Multivariable hazard ratios were estimated for different causes of death according to patterns of lifetime alcohol consumption using a competing risks approach: 111 953 men and 268 442 women from eight countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study were included. Self-reported alcohol consumption at ages 20, 30, 40 or 50 years and at enrolment were used for the analysis; 26 411 deaths were observed during an average of 12.6 years of follow-up. RESULTS: The association between lifetime alcohol use and death from cardiovascular diseases was different from the association seen for alcohol-related cancers, digestive, respiratory, external and other causes. Heavy users (>5 drinks/day for men and >2.5 drinks/day for women), regardless of time of cessation, had a 2- to 5-times higher risk of dying due to alcohol-related cancers, compared with subjects with lifetime light use (</=1 and </=0.5 drink/week for men and women, respectively). Compared with lifetime light users, men who used <5 drinks/day throughout their lifetime had a 24% lower cardiovascular disease mortality (95% confidence interval 2-41). The risk of death from coronary heart disease was also found to be 34-46% lower among women who were moderate to occasionally heavy alcohol users compared with light users. However, this relationship was only evident among men and women who had no chronic disease at enrolment. CONCLUSIONS: Limiting alcohol use throughout life is associated with a lower risk of death, largely due to cardiovascular disease but also other causes. However, the potential health benefits of alcohol use are difficult to establish due to the possibility of selection bias and competing risks related to diseases occurring later in life

Age at menopause, reproductive life span, and type 2 diabetes risk: results from the EPIC-InterAct study

Brand J.S., van der Schouw Y.T., Onland-Moret N.C., Sharp S.J., Ong K.K., Khaw K.T., Ardanaz E., Amiano P., Boeing H., Chirlaque M.D., Clavel-Chapelon F., Crowe F.L., de Lauzon-Guillain B., Duell E.J., Fagherazzi G., Franks P.W., Grioni S., Groop L.C., Kaaks R., Key T.J., Nilsson P.M., Overvad K., Palli D., Panico S., Quiros J.R., Rolandsson O., Sacerdote C., Sanchez M.J., Slimani N., Teucher B., Tjonneland A., Tumino R., van der A.DL, Feskens E.J., Langenberg C., Forouhi N.G., Riboli E., Wareham N.J.

Diabetes Care; 2013; 36(4): 1012-1019

PMID:23230098

Abstract as provided by PubMed

OBJECTIVE: Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS: Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied. RESULTS: Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and >/=55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05). CONCLUSIONS: Early menopause is associated with a greater risk of type 2 diabetes

Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study

Buckland G., Travier N., Cottet V., Gonzalez C.A., Lujan-Barroso L., Agudo A., Trichopoulou A., Lagiou P., Trichopoulos D., Peeters P.H., May A., Bueno-de-Mesquita H.B., Bvan Duijnhoven F.J., Key T.J., Allen N., Khaw K.T., Wareham N., Romieu I., McCormack V., Boutron-Ruault M., Clavel-Chapelon F., Panico S., Agnoli C., Palli D., Tumino R., Vineis P., Amiano P., Barricarte A., Rodriguez L., Sanchez M.J., Chirlaque M.D., Kaaks R., Teucher B., Boeing H., Bergmann M.M., Overvad K., Dahm C.C., Tjonneland A., Olsen A., Manjer J., Wirfalt E., Hallmans G., Johansson I., Lund E., Hjartaker A., Skeie G., Vergnaud A.C., Norat T., Romaguera D., Riboli E.

Int J Cancer; 2013; 132(12): 2918-2927

PMID:23180513

Abstract as provided by PubMed

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

Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis

Dossus L., Lukanova A., Rinaldi S., Allen N., Cust A.E., Becker S., Tjonneland A., Hansen L., Overvad K., Chabbert-Buffet N., Mesrine S., Clavel-Chapelon F., Teucher B., Chang-Claude J., Boeing H., Drogan D., Trichopoulou A., Benetou V., Bamia C., Palli D., Agnoli C., Galasso R., Tumino R., Sacerdote C., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Peeters P.H., Onland-Moret N.C., Redondo M.L., Travier N., Sanchez M.J., Altzibar J.M., Chirlaque M.D., Barricarte A., Lundin E., Khaw K.T., Wareham N., Fedirko V., Romieu I., Romaguera D., Norat T., Riboli E., Kaaks R.

Am J Epidemiol; 2013; 177(8): 787-799

PMID:23492765

Abstract as provided by PubMed

A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) alpha, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome,""steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis

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