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2011

Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Tsilidis K.K., Allen N.E., Key T.J., Dossus L., Lukanova A., Bakken K., Lund E., Fournier A., Overvad K., Hansen L., Tjonneland A., Fedirko V., Rinaldi S., Romieu I., Clavel-Chapelon F., Engel P., Kaaks R., Schutze M., Steffen A., Bamia C., Trichopoulou A., Zylis D., Masala G., Pala V., Galasso R., Tumino R., Sacerdote C., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Braem M.G., Onland-Moret N.C., Gram I.T., Rodriguez L., Travier N., Sanchez M.J., Huerta J.M., Ardanaz E., Larranaga N., Jirstrom K., Manjer J., Idahl A., Ohlson N., Khaw K.T., Wareham N., Mouw T., Norat T., Riboli E.

Br J Cancer; 2011; 105(9): 1436-1442

Abstract as provided by PubMed

Background:It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear.Methods:We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use.Results:Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59-0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs </=45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk.Conclusion:This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition

Tsilidis K.K., Allen N.E., Key T.J., Dossus L., Kaaks R., Bakken K., Lund E., Fournier A., Dahm C.C., Overvad K., Hansen L., Tjonneland A., Rinaldi S., Romieu I., Boutron-Ruault M.C., Clavel-Chapelon F., Lukanova A., Boeing H., Schutze M., Benetou V., Palli D., Berrino F., Galasso R., Tumino R., Sacerdote C., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Braem M.G., Onland-Moret N.C., Gram I.T., Rodriguez L., Duell E.J., Sanchez M.J., Huerta J.M., Ardanaz E., Amiano P., Khaw K.T., Wareham N., Riboli E.

Cancer Causes Control; 2011; 22(8): 1075-1084

Abstract as provided by PubMed

The association between menopausal hormone therapy (HT) and risk of ovarian cancer was assessed among 126,920 post-menopausal women recruited into the European Prospective Investigation into Cancer and Nutrition. After an average of 9-year follow-up, 424 incident ovarian cancers were diagnosed. Cox models adjusted for body mass index, smoking status, unilateral ovariectomy, simple hysterectomy, age at menarche, number of full-term pregnancies, and duration of oral contraceptives were used. Compared with baseline never use, current use of any HT was positively associated with risk (HR [hazard ratio], 1.29; 95% CI [confidence interval], 1.01-1.65), while former use was not (HR, 0.96; 95% CI, 0.70-1.30). Current estrogen-only HT was associated with a 63% higher risk (HR, 1.63; 95% CI, 1.08-2.47), while current estrogen plus progestin was associated with a smaller and non-significant higher risk (HR, 1.20; 95% CI, 0.89-1.62). Use of tibolone was associated with a twofold greater risk (HR, 2.19; 95% CI, 1.06-4.50), but was based on small numbers. In conclusion, women who currently use HT have a moderate increased risk of ovarian cancer, and which may be stronger for estrogen-only than estrogen plus progestin preparations

Menopausal hormone therapy and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

Tsilidis K.K., Allen N.E., Key T.J., Sanjoaquin M.A., Bakken K., Berrino F., Fournier A., Lund E., Overvad K., Olsen A., Tjonneland A., Byrnes G., Chajes V., Rinaldi S., Boutron-Ruault M.C., Clavel-Chapelon F., Chang-Claude J., Kaaks R., Bergmann M., Boeing H., Koumantaki Y., Palli D., Pala V., Panico S., Tumino R., Vineis P., Bas Bueno-de-Mesquita H., van Duijnhoven F.J., Van Gils C.H., Peeters P.H., Rodriguez L., Gonzalez C.A., Sanchez M.J., Chirlaque M.D., Barricarte A., Dorronsoro M., Khaw K.T., Rodwell S.A., Norat T., Romaguera D., Riboli E.

Int J Cancer; 2011; 128(8): 1881-1889

Abstract as provided by PubMed

Menopausal hormone therapy (HT) may influence colorectal cancer risk. A total of 136,275 postmenopausal women from the European Prospective Investigation into Cancer and Nutrition were followed for an average of 9 years, during which time 1,186 colorectal cancers were diagnosed. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by center and age, and adjusted for body mass index, smoking, diabetes, physical activity and alcohol consumption. Compared to never use of HT at study enrolment, current use of estrogen-only (HR, 1.02; 95% CI, 0.79-1.31) or estrogen plus progestin (HR, 0.94; 95% CI, 0.77-1.14) was not significantly associated with the risk of colorectal cancer, and these associations did not vary by recency, duration, route of administration, regimen or specific constituent of HT. Our results show no significant association of estrogen-only or estrogen plus progestin therapy with colorectal cancer risk

Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition

van Duijnhoven F.J., Bueno-de-Mesquita H.B., Calligaro M., Jenab M., Pischon T., Jansen E.H., Frohlich J., Ayyobi A., Overvad K., Toft-Petersen A.P., Tjonneland A., Hansen L., Boutron-Ruault M.C., Clavel-Chapelon F., Cottet V., Palli D., Tagliabue G., Panico S., Tumino R., Vineis P., Kaaks R., Teucher B., Boeing H., Drogan D., Trichopoulou A., Lagiou P., Dilis V., Peeters P.H., Siersema P.D., Rodriguez L., Gonzalez C.A., Molina-Montes E., Dorronsoro M., Tormo M.J., Barricarte A., Palmqvist R., Hallmans G., Khaw K.T., Tsilidis K.K., Crowe F.L., Chajes V., Fedirko V., Rinaldi S., Norat T., Riboli E.

Gut; 2011; 60(8): 1094-1102

Abstract as provided by PubMed

Objective To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). Design Nested case-control study. Setting The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries. Participants 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. Main outcome measures Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. Results After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. Conclusions These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation

Physical activity and lymphoid neoplasms in the European Prospective Investigation into Cancer and nutrition (EPIC)

van Veldhoven C.M., Khan A.E., Teucher B., Rohrmann S., Raaschou-Nielsen O., Tjonneland A., Overvad K., Vigl M., Boeing H., Benetou V., Trichopoulou A., Trichopoulos D., Masala G., Mattiello A., Krogh V., Tumino R., Vermeulen R., Monninkhof E., May A.M., Bueno-de-Mesquita B., Lund E., Ardanaz E., Huerta J.M., Jakszyn P., Dorronsoro M., Arguelles M., Sanchez M.J., Hallmans G., Manjer J., Borgquist S., Allen N.E., Travis R.C., Khaw K.T., Wareham N., Boffetta P., Vineis P., Riboli E.

Eur J Cancer; 2011; 47(5): 748-760

Abstract as provided by PubMed

BACKGROUND: Lymphoid neoplasms are a heterogeneous group of cancers that originate in the lymphatic cells of the immune system. Several risk factors have been identified or suggested, but they all account for only a small proportion of the lymphoid neoplasm incidence. It has been hypothesised that regular exercise may modulate the immune system and thereby reduce the risk of developing the disease. DESIGN AND METHODS: The European Investigation into Cancer and Nutrition (EPIC) cohort consists of 521,457 adults, recruited by 23 centres in 10 European countries. The analytical cohort included 343,756 participants, with 778 non-Hodgkin lymphoma (NHL) cases (376 men and 402 women) and 690 B-cell non-Hodgkin lymphoma (B-NHL) cases (326 men and 364 women). Multivariate Cox regression models were used to calculate hazard ratios (HR) for the association between total, recreational, occupational, and household physical activity and NHL and B-NHL risk, as well as the risk for several B-NHL subtypes. Models were stratified by study centre and age at recruitment and adjusted for various potential confounding factors. RESULTS: We found no evidence of any effect of total physical activity on NHL (adjusted p-trend=0.76 and 0.30 for men and women, respectively) and B-NHL risk (adjusted p-trend=0.99 and 0.21 for men and women, respectively) for either men or women. Also no robust results were found for B-NHL subtype analyses among men or women. CONCLUSIONS: This study provided no consistent evidence for an association between various physical activity measures and the risk of lymphoid neoplasms or any of the B-NHL subtypes

Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Xun W.W., Brennan P., Tjonneland A., Vogel U., Overvad K., Kaaks R., Canzian F., Boeing H., Trichopoulou A., Oustoglou E., Giotaki Z., Johansson M., Palli D., Agnoli C., Tumino R., Sacerdote C., Panico S., Bueno-de-Mesquita H.B., Peeters P.H., Lund E., Kumle M., Rodriguez L., Agudo A., Sanchez M.J., Arriola L., Chirlaque M.D., Barricarte A., Hallmans G., Rasmuson T., Khaw K.T., Wareham N., Key T., Riboli E., Vineis P.

Mutagenesis; 2011; 26(5): 657-666

Abstract as provided by PubMed

The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample

Estimated dietary intakes of flavonols, flavanones and flavones in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24 hour dietary recall cohort

Zamora-Ros R., Knaze V., Lujan-Barroso L., Slimani N., Romieu I., Fedirko V., Santucci de Magistris M., Ericson U., Amiano P., Trichopoulou A., Dilis V., Naska A., Engeset D., Skeie G., Cassidy A., Overvad K., Peeters P.H., Maria Huerta J., Sanchez M.J., Quiros J.R., Sacerdote C., Grioni S., Tumino R., Johansson G., Johansson I., Drake I., Crowe F.L., Barricarte A., Kaaks R., Teucher B., Bas Bueno-de-Mesquita H., van Rossum C.T., Norat T., Romaguera D., Vergnaud A.C., Tjonneland A., Halkjaer J., Clavel-Chapelon F., Boutron-Ruault M.C., Touillaud M., Salvini S., Khaw K.T., Wareham N., Boeing H., Forster J., Riboli E., Gonzalez C.A.

Br J Nutr; 2011; 106(12): 1915-1925

Abstract as provided by PubMed

Flavonols, flavanones and flavones (FLAV) are sub-classes of flavonoids that exert cardioprotective and anti-carcinogenic properties in vitro and in vivo. We aimed to estimate the FLAV dietary intake, their food sources and associated lifestyle factors in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. FLAV intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven study centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on FLAV was compiled using data from US Department of Agriculture and Phenol-Explorer databases and was expanded using recipes, estimations and flavonoid retention factors in order to increase its correspondence with the 24 h dietary recall. Our results showed that the highest FLAV-consuming centre was the UK health-conscious group, with 130.9 and 97.0 mg/d for men and women, respectively. The lowest FLAV intakes were 36.8 mg/d in men from Umea and 37.2 mg/d in women from Malmo (Sweden). The flavanone sub-class was the main contributor to the total FLAV intake ranging from 46.6 to 52.9 % depending on the region. Flavonols ranged from 38.5 to 47.3 % and flavones from 5.8 to 8.6 %. FLAV intake was higher in women, non-smokers, increased with level of education and physical activity. The major food sources were citrus fruits and citrus-based juices (especially for flavanones), tea, wine, other fruits and some vegetables. We concluded that the present study shows heterogeneity in intake of these three sub-classes of flavonoids across European regions and highlights differences by sex and other sociodemographic and lifestyle factors

Estimation of the intake of anthocyanidins and their food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Zamora-Ros R., Knaze V., Lujan-Barroso L., Slimani N., Romieu I., Touillaud M., Kaaks R., Teucher B., Mattiello A., Grioni S., Crowe F., Boeing H., Forster J., Quiros J.R., Molina E., Huerta J.M., Engeset D., Skeie G., Trichopoulou A., Dilis V., Tsiotas K., Peeters P.H., Khaw K.T., Wareham N., Bueno-de-Mesquita B., Ocke M.C., Olsen A., Tjonneland A., Tumino R., Johansson G., Johansson I., Ardanaz E., Sacerdote C., Sonestedt E., Ericson U., Clavel-Chapelon F., Boutron-Ruault M.C., Fagherazzi G., Salvini S., Amiano P., Riboli E., Gonzalez C.A.

Br J Nutr; 2011; 106(7): 1090-1099

Abstract as provided by PubMed

Anthocyanidins are bioactive flavonoids with potential health-promoting effects. These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved. The aim of the present study was to estimate the dietary intake of anthocyanidins, their food sources and the lifestyle factors (sex, age, BMI, smoking status, educational level and physisical activity) involved among twenty-seven centres in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthocyanidin intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven redefined centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) was compiled using data from the US Department of Agriculture and Phenol-Explorer databases and was expanded by adding recipes, estimated values and cooking factors. For men, the total anthocyanidin mean intake ranged from 19.83 (se 1.53) mg/d (Bilthoven, The Netherlands) to 64.88 (se 1.86) mg/d (Turin, Italy), whereas for women the range was 18.73 (se 2.80) mg/d (Granada, Spain) to 44.08 (se 2.45) mg/d (Turin, Italy). A clear south to north gradient intake was observed. Cyanidins and malvidins were the main anthocynidin contributors depending on the region and sex. Anthocyanidin intake was higher in non-obese older females, non-smokers, and increased with educational level and physical activity. The major food sources were fruits, wine, non-alcoholic beverages and some vegetables. The present study shows differences in both total and individual anthocyanidin intakes and various lifestyle factors throughout Europe, with some geographical variability in their food sources

2010

Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European prospective investigation into cancer and nutrition

Aleksandrova K., Jenab M., Boeing H., Jansen E., Bueno-de-Mesquita H.B., Rinaldi S., Riboli E., Overvad K., Dahm C.C., Olsen A., Tjonneland A., Boutron-Ruault M.C., Clavel-Chapelon F., Morois S., Palli D., Krogh V., Tumino R., Vineis P., Panico S., Kaaks R., Rohrmann S., Trichopoulou A., Lagiou P., Trichopoulos D., van Duijnhoven F.J., Leufkens A.M., Peeters P.H., Rodriguez L., Bonet C., Sanchez M.J., Dorronsoro M., Navarro C., Barricarte A., Palmqvist R., Hallmans G., Khaw K.T., Wareham N., Allen N.E., Spencer E., Romaguera D., Norat T., Pischon T.

Am J Epidemiol; 2010; 172(4): 407-418

Abstract as provided by PubMed

The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992-2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of >/=3.0 mg/L versus <1.0 mg/L were 1.36 (95% confidence interval (CI): 1.00, 1.85; P-trend = 0.01) for colon cancer and 1.02 (95% CI: 0.67, 1.57; P-trend = 0.65) for rectal cancer. Colon cancer risk was significantly increased in men (relative risk = 1.74, 95% CI: 1.11, 2.73; P-trend = 0.01) but not in women (relative risk = 1.06, 95% CI: 0.67, 1.68; P-trend = 0.13). Additional adjustment for C-peptide, glycated hemoglobin, and high density lipoprotein cholesterol did not attenuate these results. These data provide evidence that elevated CRP concentrations are related to a higher risk of colon cancer but not rectal cancer, predominantly among men and independently of obesity, insulin resistance, and dyslipidemia

Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition

Allen N.E., Tsilidis K.K., Key T.J., Dossus L., Kaaks R., Lund E., Bakken K., Gavrilyuk O., Overvad K., Tjonneland A., Olsen A., Fournier A., Fabre A., Clavel-Chapelon F., Chabbert-Buffet N., Sacerdote C., Krogh V., Bendinelli B., Tumino R., Panico S., Bergmann M., Schuetze M., van Duijnhoven F.J., Bueno-de-Mesquita H.B., Onland-Moret N.C., Van Gils C.H., Amiano P., Barricarte A., Chirlaque M.D., Molina-Montes M.E., Redondo M.L., Duell E.J., Khaw K.T., Wareham N., Rinaldi S., Fedirko V., Mouw T., Michaud D.S., Riboli E.

Am J Epidemiol; 2010; 172(12): 1394-1403

Abstract as provided by PubMed

Estrogen-only menopausal hormone therapy (HT) increases the risk of endometrial cancer, but less is known about the association with other types of HT. Using Cox proportional hazards regression, the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospective Investigation into Cancer and Nutrition between 1992 and 2000. After a mean follow-up period of 9 years, 601 incident cases of endometrial cancer were identified. In comparison with never users of HT, risk of endometrial cancer was increased among current users of estrogen-only HT (hazard ratio (HR) = 2.52, 95% confidence interval (CI): 1.77, 3.57), tibolone (HR = 2.96, 95% CI: 1.67, 5.26), and, to a lesser extent, estrogen-plus-progestin HT (HR = 1.41, 95% CI: 1.08, 1.83), although risks differed according to regimen and type of progestin constituent. The association of HT use with risk was stronger among women who were older, leaner, or had ever smoked cigarettes. The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk. The increased risk associated with tibolone use requires further investigation

Weight change in later life and risk of death amongst the elderly: the European Prospective Investigation into Cancer and Nutrition-Elderly Network on Ageing and Health study

Bamia C., Halkjaer J., Lagiou P., Trichopoulos D., Tjonneland A., Berentzen T.L., Overvad K., Clavel-Chapelon F., Boutron-Ruault M.C., Rohrmann S., Linseisen J., Steffen A., Boeing H., May A.M., Peeters P.H., Bas Bueno-de-Mesquita H., van den Berg S.W., Dorronsoro M., Barricarte A., Rodriguez Suarez L., Navarro C., Gonzalez C.A., Boffetta P., Pala V., Hallmans G., Trichopoulou A.

J Intern Med; 2010; 268(2): 133-144

Abstract as provided by PubMed

Objective. Later life weight change and mortality amongst elders. Design. Nested case-control study. Setting. Six countries from the European Investigation into Cancer and nutrition - Elderly, Network on Ageing and Health. Subjects. A total of 1712 deceased (cases) and 4942 alive (controls) were selected from 34 239 participants, >/= 60 years at enrolment (1992-2000) who were followed-up until March 2007. Annual weight change was estimated as the weight difference from recruitment to the most distant from-date-of-death re-assessment, divided by the respective time. Outcome measures. Mortality in relation to weight change was examined using conditional logistic regression. Results. Weight loss >1 kg year(-1) was associated with statistically significant increased death risk (OR = 1.65; 95% CI: 1.41-1.92) compared to minimal weight change (+/-1 kg year(-1)). Weight gain >1 kg year(-1) was also associated with increased risk of death (OR = 1.15; 95% CI: 0.98-1.37), but this was evident and statistically significant only amongst overweight/obese (OR = 1.55; 95% CI: 1.17-2.05). In analyses by time interval since weight re-assessment, the association of mortality with weight loss was stronger for the interval proximal (<1 year) to death (OR = 3.10; 95% CI: 2.03-4.72). The association of mortality with weight gain was stronger at the interval of more than 3 years and statistically significant only amongst overweight/obese (OR = 1.58; 95% CI: 1.07-2.33). Similar patterns were observed regarding death from circulatory diseases and cancer. Conclusions. In elderly, stable body weight is a predictor of lower subsequent mortality. Weight loss is associated with increased mortality, particularly short-term, probably reflecting underlying nosology. Weight gain, especially amongst overweight/obese elders, is also associated with increased mortality, particularly longer term

Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Boffetta P., Couto E., Wichmann J., Ferrari P., Trichopoulos D., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Buchner F.L., Key T., Boeing H., Nothlings U., Linseisen J., Gonzalez C.A., Overvad K., Nielsen M.R., Tjonneland A., Olsen A., Clavel-Chapelon F., Boutron-Ruault M.C., Morois S., Lagiou P., Naska A., Benetou V., Kaaks R., Rohrmann S., Panico S., Sieri S., Vineis P., Palli D., Van Gils C.H., Peeters P.H., Lund E., Brustad M., Engeset D., Huerta J.M., Rodriguez L., Sanchez M.J., Dorronsoro M., Barricarte A., Hallmans G., Johansson I., Manjer J., Sonestedt E., Allen N.E., Bingham S., Khaw K.T., Slimani N., Jenab M., Mouw T., Norat T., Riboli E., Trichopoulou A.

J Natl Cancer Inst; 2010; 102(8): 529-537

Abstract as provided by PubMed

BACKGROUND: It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk. METHODS: We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking. RESULTS: Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol. CONCLUSIONS: A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation

Fruits and vegetables consumption and the risk of histological subtypes of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Buchner F.L., Bueno-de-Mesquita H.B., Linseisen J., Boshuizen H.C., Kiemeney L.A., Ros M.M., Overvad K., Hansen L., Tjonneland A., Raaschou-Nielsen O., Clavel-Chapelon F., Boutron-Ruault M.C., Touillaud M., Kaaks R., Rohrmann S., Boeing H., Nothlings U., Trichopoulou A., Zylis D., Dilis V., Palli D., Sieri S., Vineis P., Tumino R., Panico S., Peeters P.H., Van Gils C.H., Lund E., Gram I.T., Braaten T., Martinez C., Agudo A., Arriola L., Ardanaz E., Navarro C., Rodriguez L., Manjer J., Wirfalt E., Hallmans G., Rasmuson T., Key T.J., Roddam A.W., Bingham S., Khaw K.T., Slimani N., Bofetta P., Byrnes G., Norat T., Michaud D., Riboli E.

Cancer Causes Control; 2010; 21(3): 357-371

Abstract as provided by PubMed

OBJECTIVE: To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation into Cancer and Nutrition study. METHODS: Multivariable Cox proportional hazard models were used to analyze the data. A calibration study in a subsample was used to reduce dietary measurement errors. RESULTS: During a mean follow-up of 8.7 years, 1,830 incident cases of lung cancer (574 adenocarcinoma, 286 small cell, 137 large cell, 363 squamous cell, 470 other histologies) were identified. In line with our previous conclusions, we found that after calibration a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk (HR 0.94; 95% CI 0.89-0.99). This was also seen among current smokers (HR 0.93; 95% CI 0.90-0.97). Risks of squamous cell carcinomas in current smokers were reduced for an increase of 100 g/day of fruit and vegetables combined (HR 0.85; 95% CI 0.76-0.94), while no clear effects were seen for the other histological subtypes. CONCLUSION: We observed inverse associations between the consumption of vegetables and fruits and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer. In current smokers, consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas

Variety in fruit and vegetable consumption and the risk of lung cancer in the European prospective investigation into cancer and nutrition

Buchner F.L., Bueno-de-Mesquita H.B., Ros M.M., Overvad K., Dahm C.C., Hansen L., Tjonneland A., Clavel-Chapelon F., Boutron-Ruault M.C., Touillaud M., Kaaks R., Rohrmann S., Boeing H., Nothlings U., Trichopoulou A., Zylis D., Dilis V., Palli D., Sieri S., Vineis P., Tumino R., Panico S., Peeters P.H., Van Gils C.H., Lund E., Gram I.T., Braaten T., Sanchez M.J., Agudo A., Larranaga N., Ardanaz E., Navarro C., Arguelles M.V., Manjer J., Wirfalt E., Hallmans G., Rasmuson T., Key T.J., Khaw K.T., Wareham N., Slimani N., Vergnaud A.C., Xun W.W., Kiemeney L.A., Riboli E.

Cancer Epidemiol Biomarkers Prev; 2010; 19(9): 2278-2286

Abstract as provided by PubMed

BACKGROUND: We investigated whether a varied consumption of vegetables and fruits is associated with lower lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study. METHODS: After a mean follow-up of 8.7 years, 1,613 of 452,187 participants with complete information were diagnosed with lung cancer. Diet diversity scores (DDS) were used to quantify the variety in fruit and vegetable consumption. Multivariable proportional hazards models were used to assess the associations between DDS and lung cancer risk. All models were adjusted for smoking behavior and the total consumption of fruit and vegetables. RESULTS: With increasing variety in vegetable subgroups, risk of lung cancer decreases [hazard ratios (HR), 0.77; 95% confidence interval (CI), 0.64-0.94 highest versus lowest quartile; P trend = 0.02]. This inverse association is restricted to current smokers (HR, 0.73; 95% CI, 0.57-0.93 highest versus lowest quartile; P trend = 0.03). In continuous analyses, in current smokers, lower risks were observed for squamous cell carcinomas with more variety in fruit and vegetable products combined (HR/two products, 0.88; 95% CI, 0.82-0.95), vegetable subgroups (HR/subgroup, 0.88; 95% CI, 0.79-0.97), vegetable products (HR/two products, 0.87; 95% CI, 0.79-0.96), and fruit products (HR/two products, 0.84; 95% CI, 0.72-0.97). CONCLUSION: Variety in vegetable consumption was inversely associated with lung cancer risk among current smokers. Risk of squamous cell carcinomas was reduced with increasing variety in fruit and/or vegetable consumption, which was mainly driven by the effect in current smokers. Impact: Independent from quantity of consumption, variety in fruit and vegetable consumption may decrease lung cancer risk. Cancer Epidemiol Biomarkers Prev; 19(9); 2278-86. (c)2010 AACR

Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study

Buckland G., Agudo A., Lujan L., Jakszyn P., Bueno-de-Mesquita H.B., Palli D., Boeing H., Carneiro F., Krogh V., Sacerdote C., Tumino R., Panico S., Nesi G., Manjer J., Regner S., Johansson I., Stenling R., Sanchez M.J., Dorronsoro M., Barricarte A., Navarro C., Quiros J.R., Allen N.E., Key T.J., Bingham S., Kaaks R., Overvad K., Jensen M., Olsen A., Tjonneland A., Peeters P.H., Numans M.E., Ocke M.C., Clavel-Chapelon F., Morois S., Boutron-Ruault M.C., Trichopoulou A., Lagiou P., Trichopoulos D., Lund E., Couto E., Boffetta P., Jenab M., Riboli E., Romaguera D., Mouw T., Gonzalez C.A.

Am J Clin Nutr; 2010; 91(2): 381-390

Abstract as provided by PubMed

BACKGROUND: The Mediterranean dietary pattern is believed to protect against cancer, although evidence from cohort studies that have examined particular cancer sites is limited. OBJECTIVE: We aimed to explore the association between adherence to a relative Mediterranean diet (rMED) and incident gastric adenocarcinoma (GC) within the European Prospective Investigation into Cancer and Nutrition study. DESIGN: The study included 485,044 subjects (144,577 men) aged 35-70 y from 10 European countries. At recruitment, dietary and lifestyle information was collected. An 18-unit rMED score, incorporating 9 key components of the Mediterranean diet, was used to estimate rMED adherence. The association between rMED and GC with respect to anatomic location (cardia and noncardia) and histologic types (diffuse and intestinal) was investigated. A calibration study in a subsample was used to control for dietary measurement error. RESULTS: After a mean follow-up of 8.9 y, 449 validated incident GC cases were identified and used in the analysis. After stratification by center and age and adjustment for recognized cancer risk factors, high compared with low rMED adherence was associated with a significant reduction in GC risk (hazard ratio: 0.67; 95% CI: 0.47, 0.94). A 1-unit increase in the rMED score was associated with a decreased risk of GC of 5% (95% CI: 0.91, 0.99). There was no evidence of heterogeneity between different anatomic locations or histologic types. The calibrated results showed similar trends (overall hazard ratio for GC: 0.93; 95% CI: 0.89, 0.99). CONCLUSION: Greater adherence to an rMED is associated with a significant reduction in the risk of incident GC

Obesity, inflammatory markers, and endometrial cancer risk: a prospective case-control study

Dossus L., Rinaldi S., Becker S., Lukanova A., Tjonneland A., Olsen A., Stegger J., Overvad K., Chabbert-Buffet N., Jimenez-Corona A., Clavel-Chapelon F., Rohrmann S., Teucher B., Boeing H., Schutze M., Trichopoulou A., Benetou V., Lagiou P., Palli D., Berrino F., Panico S., Tumino R., Sacerdote C., Redondo M.L., Travier N., Sanchez M.J., Altzibar J.M., Chirlaque M.D., Ardanaz E., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Onland-Moret N.C., Peeters P.H., Hallmans G., Lundin E., Khaw K.T., Wareham N., Allen N., Key T.J., Slimani N., Hainaut P., Romaguera D., Norat T., Riboli E., Kaaks R.

Endocr Relat Cancer; 2010; 17(4): 1007-1019

Abstract as provided by PubMed

Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case-control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03-2.41, P(trend)=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, P(trend)=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, P(trend)=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated ( approximately 10-20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu

Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

Dossus L., Allen N., Kaaks R., Bakken K., Lund E., Tjonneland A., Olsen A., Overvad K., Clavel-Chapelon F., Fournier A., Chabbert-Buffet N., Boeing H., Schutze M., Trichopoulou A., Trichopoulos D., Lagiou P., Palli D., Krogh V., Tumino R., Vineis P., Mattiello A., Bueno-de-Mesquita H.B., Onland-Moret N.C., Peeters P.H., Dumeaux V., Redondo M.L., Duell E., Sanchez-Cantalejo E., Arriola L., Chirlaque M.D., Ardanaz E., Manjer J., Borgquist S., Lukanova A., Lundin E., Khaw K.T., Wareham N., Key T., Chajes V., Rinaldi S., Slimani N., Mouw T., Gallo V., Riboli E.

Int J Cancer; 2010; 127(2): 442-451

Abstract as provided by PubMed

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis

Tumor necrosis factor (TNF)-alpha, soluble TNF receptors and endometrial cancer risk: The EPIC study

Dossus L., Becker S., Rinaldi S., Lukanova A., Tjonneland A., Olsen A., Overvad K., Chabbert-Buffet N., Boutron-Ruault M.C., Clavel-Chapelon F., Teucher B., Chang-Claude J., Pischon T., Boeing H., Trichopoulou A., Benetou V., Valanou E., Palli D., Sieri S., Tumino R., Sacerdote C., Galasso R., Redondo M.L., Bonet Bonet C., Molina-Montes E., Altzibar J.M., Chirlaque M.D., Ardanaz E., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Peeters P.H., Onland-Moret N.C., Lundin E., Idahl A., Khaw K.T., Wareham N., Allen N., Romieu I., Fedirko V., Hainaut P., Romaguera D., Norat T., Riboli E., Kaaks R.

Int J Cancer; 2010; 8(2032): 2037

Abstract as provided by PubMed

Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-alpha (TNF-alpha), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology.We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) to examine the association of TNF-alpha and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided.We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-alpha (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, P(trend)=0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, P(trend)=0.07), and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, P(trend)=0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates.Our data show that elevated pre-diagnostic concentrations of TNF-alpha and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies

Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition

Duell E.J., Travier N., Lujan-Barroso L., Boutron-Ruault M.C., Clavel-Chapelon F., Palli D., Krogh V., Mattiello A., Tumino R., Sacerdote C., Rodriguez L., Sanchez-Cantalejo E., Navarro C., Barricarte A., Dorronsoro M., Khaw K.T., Wareham N., Allen N.E., Tsilidis K.K., Bueno-de-Mesquita H.B., Jeurnink S.M., Numans M.E., Peeters P.H., Lagiou P., Valanou E., Trichopoulou A., Kaaks R., Lukanova-McGregor A., Bergman M.M., Boeing H., Manjer J., Lindkvist B., Stenling R., Hallmans G., Dahm C.C., Overvad K., Olsen A., Tjonneland A., Bakken K., Lund E., Jenab M., McCormack V., Rinaldi S., Michaud D., Mouw T., Nesi G., Carneiro F., Riboli E., Gonzalez C.A.

Am J Epidemiol; 2010; 172(12): 1384-1393

Abstract as provided by PubMed

The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women

Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk

Eussen S.J., Vollset S.E., Hustad S., Midttun O., Meyer K., Fredriksen A., Ueland P.M., Jenab M., Slimani N., Boffetta P., Overvad K., Thorlacius-Ussing O., Tjonneland A., Olsen A., Clavel-Chapelon F., Boutron-Ruault M.C., Morois S., Weikert C., Pischon T., Linseisen J., Kaaks R., Trichopoulou A., Zilis D., Katsoulis M., Palli D., Pala V., Vineis P., Tumino R., Panico S., Peeters P.H., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Skeie G., Munoz X., Martinez C., Dorronsoro M., Ardanaz E., Navarro C., Rodriguez L., Van Guelpen B., Palmqvist R., Manjer J., Ericson U., Bingham S., Khaw K.T., Norat T., Riboli E.

Cancer Epidemiol Biomarkers Prev; 2010; 19(10): 2549-2561

Abstract as provided by PubMed

BACKGROUND: B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive. METHODS: We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, including 1,365 incident colorectal cancer cases and 2,319 controls matched for study center, age, and sex. We measured the sum of B2 species riboflavin and flavin mononucleotide, and the sum of B6 species pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as well as vitamin B12 in plasma samples collected at baseline. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for colorectal cancer were estimated using conditional logistic regression, adjusted for smoking, education, physical activity, body mass index, alcohol consumption, and intakes of fiber and red and processed meat. RESULTS: The relative risks comparing highest to lowest quintile were 0.71 [95% confidence interval (95% CI), 0.56-0.91; P(trend) = 0.02] for vitamin B2, 0.68 (95% CI, 0.53-0.87; P(trend) <0.001) for vitamin B6, and 1.02 (95% CI, 0.80-1.29; P(trend) = 0.19) for vitamin B12. The associations for vitamin B6 were stronger in males who consumed >/=30 g alcohol/day. The polymorphisms were not associated with colorectal cancer. CONCLUSIONS: Higher plasma concentrations of vitamins B2 and B6 are associated with a lower colorectal cancer risk. IMPACT: This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer

Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition

Eussen S.J., Vollset S.E., Hustad S., Midttun O., Meyer K., Fredriksen A., Ueland P.M., Jenab M., Slimani N., Ferrari P., Agudo A., Sala N., Capella G., Del Giudice G., Palli D., Boeing H., Weikert C., Bueno-de-Mesquita H.B., Buchner F.L., Carneiro F., Berrino F., Vineis P., Tumino R., Panico S., Berglund G., Manjer J., Stenling R., Hallmans G., Martinez C., Arrizola L., Barricarte A., Navarro C., Rodriguez L., Bingham S., Linseisen J., Kaaks R., Overvad K., Tjonneland A., Peeters P.H., Numans M.E., Clavel-Chapelon F., Boutron-Ruault M.C., Morois S., Trichopoulou A., Lund E., Plebani M., Riboli E., Gonzalez C.A.

Cancer Epidemiol Biomarkers Prev; 2010; 19(1): 28-38

Abstract as provided by PubMed

B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk

Plasma folate, related genetic variants, and colorectal cancer risk in EPIC

Eussen S.J., Vollset S.E., Igland J., Meyer K., Fredriksen A., Ueland P.M., Jenab M., Slimani N., Boffetta P., Overvad K., Tjonneland A., Olsen A., Clavel-Chapelon F., Boutron-Ruault M.C., Morois S., Weikert C., Pischon T., Linseisen J., Kaaks R., Trichopoulou A., Zilis D., Katsoulis M., Palli D., Berrino F., Vineis P., Tumino R., Panico S., Peeters P.H., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Gram I.T., Skeie G., Lund E., Gonzalez C.A., Martinez C., Dorronsoro M., Ardanaz E., Navarro C., Rodriguez L., Van Guelpen B., Palmqvist R., Manjer J., Ericson U., Bingham S., Khaw K.T., Norat T., Riboli E.

Cancer Epidemiol Biomarkers Prev; 2010; 19(5): 1328-1340

Abstract as provided by PubMed

BACKGROUND: A potential dual role of folate in colorectal cancer (CRC) is currently subject to debate. We investigate the associations between plasma folate, several relevant folate-related polymorphisms, and CRC risk within the large European Prospective Investigation into Cancer and Nutrition cohort. METHODS: In this nested case-control study, 1,367 incident CRC cases were matched to 2,325 controls for study center, age, and sex. Risk ratios (RR) were estimated with conditional logistic regression and adjusted for smoking, education, physical activity, and intake of alcohol and fiber. RESULTS: Overall analyses did not reveal associations of plasma folate with CRC. The RR (95% confidence interval; Ptrend) for the fifth versus the first quintile of folate status was 0.94 (0.74-1.20; 0.44). The polymorphisms MTHFR677C-->T, MTHFR1298A-->C, MTR2756A-->G, MTRR66A-->G, and MTHFD11958G-->A were not associated with CRC risk. However, in individuals with the lowest plasma folate concentrations, the MTHFR 677TT genotype showed a statistically nonsignificant increased CRC risk [RR (95% CI; Ptrend) TT versus CC=1.39 (0.87-2.21); 0.12], whereas those with the highest folate concentrations showed a nonsignificant decreased CRC risk [RR TT versus CC=0.74 (0.39-1.37); 0.34]. The SLC19A180G-->A showed a positive association with CRC risk [RR AA versus GG 1.30 (1.06-1.59); <0.01]. CONCLUSIONS: This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms. IMPACT: Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions

Region-specific nutrient intake patterns exhibit a geographical gradient within and between European countries

Freisling H., Fahey M.T., Moskal A., Ocke M.C., Ferrari P., Jenab M., Norat T., Naska A., Welch A.A., Navarro C., Schulz M., Wirfalt E., Casagrande C., Amiano P., Ardanaz E., Parr C., Engeset D., Grioni S., Sera F., Bueno-de-Mesquita B., van der Schouw Y.T., Touvier M., Boutron-Ruault M.C., Halkjaer J., Dahm C.C., Khaw K.T., Crowe F., Linseisen J., Kroger J., Huybrechts I., Deharveng G., Manjer J., Agren A., Trichopoulou A., Tsiotas K., Riboli E., Bingham S., Slimani N.

J Nutr; 2010; 140(7): 1280-1286

Abstract as provided by PubMed

Until recently, the study of nutrient patterns was hampered at an international level by a lack of standardization of both dietary methods and nutrient databases. We aimed to describe the diversity of nutrient patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) study at population level as a starting point for future nutrient pattern analyses and their associations with chronic diseases in multi-center studies. In this cross-sectional study, 36,034 persons aged 35-74 y were administered a single, standardized 24-h dietary recall. Intake of 25 nutrients (excluding intake from dietary supplements) was estimated using a standardized nutrient database. We used a graphic presentation of mean nutrient intakes by region and sex relative to the overall EPIC means to contrast patterns within and between 10 European countries. In Mediterranean regions, including Greece, Italy, and the southern centers of Spain, the nutrient pattern was dominated by relatively high intakes of vitamin E and monounsaturated fatty acids (MUFA), whereas intakes of retinol and vitamin D were relatively low. In contrast, in Nordic countries, including Norway, Sweden, and Denmark, reported intake of these same nutrients resulted in almost the opposite pattern. Population groups in Germany, The Netherlands, and the UK shared a fatty acid pattern of relatively high intakes of PUFA and SFA and relatively low intakes of MUFA, in combination with a relatively high intake of sugar. We confirmed large variability in nutrient intakes across the EPIC study populations and identified 3 main region-specific patterns with a geographical gradient within and between European countries

Second-hand Smoke, Cotinine Levels, and Risk of Circulatory Mortality in a Large Cohort Study of Never-Smokers

Gallo V., Neasham D., Airoldi L., Ferrari P., Jenab M., Boffetta P., Overvad K., Tjonneland A., Clavel-Chapelon F., Boeing H., Pala V., Palli D., Panico S., Tumino R., Arriola L., Lund E., Bueno-de-Mesquita B., Peeters P.H., Melander O., Hallmans G., Riboli E., Saracci R., Vineis P.

Epidemiology; 2010; 21(2): 207-214

Abstract as provided by PubMed

BACKGROUND:: Exposure to second-hand smoke has been shown to be associated with increased cardiovascular mortality in several, but not all, epidemiologic studies. Our aim was to investigate the risk of circulatory death associated with exposure to second-hand smoke in never-smokers in a very large prospective study, the European Prospective Investigation into Cancer and Nutrition. A secondary aim was to use cotinine levels for cross-validating self-reported second-hand smoke exposure. METHODS:: Cox proportional hazard models were used to investigate the risk of death due to circulatory causes associated with second-hand smoke exposure in 135,233 never-smokers. Exposure to second-hand smoke was assessed through a questionnaire at enrollment and then validated against plasma cotinine measurements in a subsample. RESULTS:: Study participants who reported second-hand smoke exposure at home had higher cotinine levels (median plasma cotinine concentration in exposed = 0.82 mug/L; in those unexposed 0.02 mug/L). Second-hand smoke exposure at home was associated with an increased risk of dying from cardiovascular diseases (hazard ratio [HR] = 1.38 [95% confidence interval = 1.01-1.90]), all circulatory diseases (1.28 [0.98-1.69]), and coronary heart disease (1.31 [0.83-2.08]) after adjustment for age, sex, education, physical activity, and body mass index. Dose-response relationships were observed between exposure to second-hand smoke at home and risk of circulatory death (HR per each additional hour/d = 1.25 [1.04-1.50]). Having a partner who smokes more than 30 cigarettes per day considerably increased the risk of a circulatory death (2.94 [1.11-7.78]). Second-hand smoke exposure at home was not associated with total mortality (1.03 [0.93-1.13]). DISCUSSION:: Exposure to second-hand smoke at home (as confirmed by plasma cotinine levels) increases the risk of cardiovascular mortality

Level of education and the risk of lymphoma in the European prospective investigation into cancer and nutrition

Hermann S., Rohrmann S., Linseisen J., Nieters A., Khan A., Gallo V., Overvad K., Tjonneland A., Raaschou-Nielsen O., Bergmann M.M., Boeing H., Becker N., Kaaks R., Bueno-de-Mesquita H.B., May A.M., Vermeulen R.C., Bingham S., Khaw K.T., Key T.J., Travis R.C., Trichopoulou A., Georgila C., Triantafylou D., Celentano E., Krogh V., Masala G., Tumino R., Agudo A., Altzibar J.M., Ardanaz E., Martinez-Garcia C., Suarez M.V., Tormo M.J., Braaten T., Lund E., Manjer J., Zackrisson S., Hallmans G., Malmer B., Boffetta P., Brennan P., Slimani N., Vineis P., Riboli E.

J Cancer Res Clin Oncol; 2010; 136(1): 71-77

Abstract as provided by PubMed

INTRODUCTION: Lymphomas belong to the few cancer sites with increasing incidence over past decades, and only a few risk factors have been established. We explored the association between education and the incidence of lymphoma in the prospective EPIC study. MATERIALS AND METHODS: Within 3,567,410 person-years of follow-up, 1,319 lymphoma cases [1,253 non-Hodgkin lymphomas (NHL) and 66 Hodgkin lymphomas (HL)] were identified. Cox proportional hazard regression was used to examine the association between highest educational level (primary school or less, technical/professional school, secondary school, university) and lymphoma risk. RESULTS: Overall, no consistent associations between educational level and lymphoma risk were observed; however, associations were found for sub-groups of the cohort. We observed a higher risk of B-NHL (HR = 1.31, 95% CI = 1.02-1.68; n = 583) in women with the highest education level (university) but not in men. Concerning sub-classes of B-NHL, a positive association between education and risk of B cell chronic lymphatic leukaemia (BCLL) was observed only in women. In both genders, the risk of diffuse large B cell lymphoma (DLBCL) was significantly lower for subjects with university degree (HR = 0.46, 95% CI = 0.27-0.79) versus lowest educational level. No association was found for HL. CONCLUSION: We could not confirm an overall consistent association of education and risk of HL or NHL in this large prospective study; although, education was positively related to the incidence of BCLL and B-NHL (in women) but inversely to incidence of DLBCL. Due to limited number of cases in sub-classes and the large number of comparisons, the possibility of chance findings can not be excluded

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