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2010

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

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

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

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

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

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

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

Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

Hoeft B., Linseisen J., Beckmann L., Muller-Decker K., Canzian F., Husing A., Kaaks R., Vogel U., Jakobsen M.U., Overvad K., Hansen R.D., Knuppel S., Boeing H., Trichopoulou A., Koumantaki Y., Trichopoulos D., Berrino F., Palli D., Panico S., Tumino R., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Van Gils C.H., Peeters P.H., Dumeaux V., Lund E., Huerta Castano J.M., Munoz X., Rodriguez L., Barricarte A., Manjer J., Jirstrom K., Van Guelpen B., Hallmans G., Spencer E.A., Crowe F.L., Khaw K.T., Wareham N., Morois S., Boutron-Ruault M.C., Clavel-Chapelon F., Chajes V., Jenab M., Boffetta P., Vineis P., Mouw T., Norat T., Riboli E., Nieters A.

Carcinogenesis; 2010; 31(3): 466-472

Abstract as provided by PubMed

Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred and ninety two single-nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse association (P < 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P < 0.001 and P = 0.003, respectively) associated with higher risk of CRC. Based on these data, we present for the first time the association of HPGD variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk

Prospective study of physical activity and risk of primary adenocarcinomas of the oesophagus and stomach in the EPIC (European Prospective Investigation into Cancer and nutrition) cohort

Huerta J.M., Navarro C., Chirlaque M.D., Tormo M.J., Steindorf K., Buckland G., Carneiro F., Johnsen N.F., Overvad K., Stegger J., Tjonneland A., Boutron-Ruault M.C., Clavel-Chapelon F., Morois S., Boeing H., Kaaks R., Rohrmann S., Vigl M., Lagiou P., Trichopoulos D., Trichopoulou A., Bas Bueno-de-Mesquita H., Monninkhof E.M., Numans M.E., Peeters P.H., Mattiello A., Pala V., Palli D., Tumino R., Vineis P., Agudo A., Ardanaz E., Arriola L., Molina-Montes E., Rodriguez L., Lindkvist B., Manjer J., Stenling R., Lund E., Crowe F.L., Key T.J., Khaw K.T., Wareham N.J., Jenab M., Norat T., Romaguera D., Riboli E., Gonzalez C.A.

Cancer Causes Control; 2010; 21(5): 657-669

Abstract as provided by PubMed

OBJECTIVE: To analyse the association between types of physical activity (occupational, recreational and household, vigorous and overall) and risk of primary oesophageal (OAC) or gastric adenocarcinoma (GAC). METHODS: From nine European countries, 420,449 participants were recruited between 1991 and 2000 and followed-up for a mean of 8.8 years to register incident GAC and OAC. Information on physical activity (PA), diet, lifestyle and health-related variables was obtained at baseline. Helicobacter pylori infection status was considered in a subset of 1,211 participants. Analyses were repeated by tumour site (cardia/non-cardia) and histological type (intestinal/diffuse). RESULTS: During the follow-up, 410 GAC and 80 OAC occurred. A lower risk of overall and non-cardia GAC was found for increasing levels of a PA index which combined occupational PA with weekly time spent in sports and cycling. The hazard ratio (HR) of GAC was 0.69, 95% CI: 0.50-0.94, for the comparison between active and inactive participants according to the PA index (HR = 0.44, 95% CI:0.26-0.74, for non-cardia GAC). No effect was found for cardia tumours or histological subtypes of GAC. PA of any kind was not associated with OAC. CONCLUSIONS: Overall and distal (non-cardia) gastric tumours were inversely associated with time spent on cycling and sports and a total PA index. No association was found for any type of PA and risk of cardia cancers of the stomach

Serum B vitamin levels and risk of lung cancer

Johansson M., Relton C., Ueland P.M., Vollset S.E., Midttun O., Nygard O., Slimani N., Boffetta P., Jenab M., Clavel-Chapelon F., Boutron-Ruault M.C., Fagherazzi G., Kaaks R., Rohrmann S., Boeing H., Weikert C., Bueno-de-Mesquita H.B., Ros M.M., Van Gils C.H., Peeters P.H., Agudo A., Barricarte A., Navarro C., Rodriguez L., Sanchez M.J., 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., Riboli E., Vineis P., Brennan P.

JAMA; 2010; 303(23): 2377-2385

Abstract as provided by PubMed

CONTEXT: B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk. OBJECTIVE: To investigate if 1-carbon metabolism factors are associated with onset of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1770 control participants were individually matched by country, sex, date of birth, and date of blood collection. Serum levels were measured for 6 factors of 1-carbon metabolism and cotinine. MAIN OUTCOME MEASURE: Odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B(2), B(6), folate [B(9)], and B(12)), methionine, and homocysteine. RESULTS: Within the entire EPIC cohort, the age-standardized incidence rates of lung cancer (standardized to the world population, aged 35-79 years) were 6.6, 44.9, and 156.1 per 100,000 person-years among never, former, and current smokers for men, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9 per 100,000 person-years, respectively. After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B(6) (fourth vs first quartile OR, 0.44; 95% confidence interval [CI], 0.33-0.60; P for trend <.000001), as well as for serum methionine (fourth vs first quartile OR, 0.52; 95% CI, 0.39-0.69; P for trend <.000001). Similar and consistent decreases in risk were observed in never, former, and current smokers, indicating that results were not due to confounding by smoking. The magnitude of risk was also constant with increasing length of follow-up, indicating that the associations were not explained by preclinical disease. A lower risk was also seen for serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51-0.90; P for trend = .001), although this was apparent only for former and current smokers. When participants were classified by median levels of serum methionine and B(6), having above-median levels of both was associated with a lower lung cancer risk overall (OR, 0.41; 95% CI, 0.31-0.54), as well as separately among never (OR, 0.36; 95% CI, 0.18-0.72), former (OR, 0.51; 95% CI, 0.34-0.76), and current smokers (OR, 0.42; 95% CI, 0.27-0.65). CONCLUSION: Serum levels of vitamin B(6) and methionine were inversely associated with risk of lung cancer

Anthropometric measures and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition

Lahmann P.H., Cust A.E., Friedenreich C.M., Schulz M., Lukanova A., Kaaks R., Lundin E., Tjonneland A., Halkjaer J., Severinsen M.T., Overvad K., Fournier A., Chabbert-Buffet N., Clavel-Chapelon F., Dossus L., Pischon T., Boeing H., Trichopoulou A., Lagiou P., Naska A., Palli D., Grioni S., Mattiello A., Tumino R., Sacerdote C., Redondo M.L., Jakszyn P., Sanchez M.J., Tormo M.J., Ardanaz E., Arriola L., Manjer J., Jirstrom K., Bas Bueno-de-Mesquita H., May A.M., Peeters P.H., Onland-Moret N.C., Bingham S., Khaw K.T., Allen N.E., Spencer E., Rinaldi S., Slimani N., Chajes V., Michaud D., Norat T., Riboli E.

Int J Cancer; 2010; 126(10): 2404-2415

Abstract as provided by PubMed

We examined the associations of measured anthropometric factors, including general and central adiposity and height, with ovarian cancer risk. We also investigated these associations by menopausal status and for specific histological subtypes. Among 226,798 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, there were 611 incident cases of primary, malignant, epithelial ovarian cancer diagnosed during a mean 8.9 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. Compared to women with body mass index (BMI) < 25 kg/m2, obesity (BMI > or = 30 kg/m2) was associated with excess ovarian cancer risk for all women combined (HR = 1.33, 95% CI = 1.05-1.68; p(trend) = 0.02) and postmenopausal women (HR = 1.59, 95% CI = 1.20-2.10; p(trend) = 0.001), but the association was weaker for premenopausal women (HR = 1.16, 95% CI = 0.65-2.06; p(trend) = 0.65). Neither height or weight gain, nor BMI-adjusted measures of fat distribution assessed by waist circumference, waist-hip ratio (WHR) or hip circumference were associated with overall risk. WHR was related to increased risk of mucinous tumors (BMI-adjusted HR per 0.05 unit increment = 1.17, 95% CI = 1.00-1.38). For all women combined, no other significant associations with risk were observed for specific histological subtypes. This large, prospective study provides evidence that obesity is an important modifiable risk factor for epithelial ovarian cancer, particularly among postmenopausal women

Cigar and pipe smoking and cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

McCormack V.A., Agudo A., Dahm C.C., Overvad K., Olsen A., Tjonneland A., Kaaks R., Boeing H., Manjer J., Almquist M., Hallmans G., Johansson I., Chirlaque M.D., Barricarte A., Dorronsoro M., Rodriguez L., Redondo M.L., Khaw K.T., Wareham N., Allen N., Key T., Riboli E., Boffetta P.

Int J Cancer; 2010; 127(10): 2402-2411

Abstract as provided by PubMed

The carcinogenicity of cigar and pipe smoking is established but the effect of detailed smoking characteristics is less well defined. We examined the effects on cancer incidence of exclusive cigar and pipe smoking, and in combination with cigarettes, among 102,395 men from Denmark, Germany, Spain, Sweden and the United Kingdom in the EPIC cohort. Hazard ratios (HR) and their 95% confidence intervals (CI) for cancer during a median 9-year follow-up from ages 35 to 70 years were estimated using proportional hazards models. Compared to never smokers, HR of cancers of lung, upper aerodigestive tract and bladder combined was 2.2 (95% CI: 1.3, 3.8) for exclusive cigar smokers (16 cases), 3.0 (2.1, 4.5) for exclusive pipe smokers (33 cases) and 5.3 (4.4, 6.4) for exclusive cigarette smokers (1,069 cases). For each smoking type, effects were stronger in current smokers than in ex-smokers and in inhalers than in non-inhalers. Ever smokers of both cigarettes and cigars [HR 5.7 (4.4, 7.3), 120 cases] and cigarettes and pipes [5.1 (4.1, 6.4), 247 cases] had as high a raised risk as had exclusive cigarette smokers. In these smokers, the magnitude of the raised risk was smaller if they had switched to cigars or pipes only (i.e., quit cigarettes) and had not compensated with greater smoking intensity. Cigar and pipe smoking is not a safe alternative to cigarette smoking. The lower cancer risk of cigar and pipe smokers as compared to cigarette smokers is explained by lesser degree of inhalation and lower smoking intensity

Occupational exposures contribute to educational inequalities in lung cancer incidence among men: Evidence from the EPIC prospective cohort study

Menvielle G., Boshuizen H., Kunst A.E., Vineis P., Dalton S.O., Bergmann M.M., Hermann S., Veglia F., Ferrari P., Overvad K., Raaschou-Nielsen O., Tjonneland A., Kaaks R., Linseisen J., Palli D., Krogh V., Tumino R., Rodriguez L., Agudo A., Sanchez M.J., Arozena J.M., Cirera L., Ardanaz E., Bingham S., Khaw K.T., Boffetta P., Duell E., Slimani N., Gallo V., Riboli E., Bas Bueno-de-Mesquita H.

Int J Cancer; 2010; 126(8): 1928-1935

Abstract as provided by PubMed

The aim of this study is to investigate to what extent occupational exposures may explain socioeconomic inequalities in lung cancer incidence after adjusting for smoking and dietary factors. Analyses were based on a subsample of the European Prospective Investigation into Cancer and Nutrition (EPIC study), a prospective cohort. The analyses included 703 incident lung cancer cases among men in Denmark, the United Kingdom, Germany, Italy, Spain and Greece. The socioeconomic position was measured using the highest level of education. The estimates of relative indices of inequality (RII) were computed with Cox regression models. We first adjusted for smoking (with detailed information on duration and quantity) and dietary factors (fruits and vegetables consumption) and then for occupational exposures. The exposure to three carcinogens [asbestos, heavy metals and polycyclic aromatic hydrocarbons (PAH)] was analyzed. The occupational exposures explained 14% of the socioeconomic inequalities remaining after adjustment for smoking and fruits and vegetables consumption. The inequalities remained nevertheless statistically significant. The RII decreased from 1.87 (95% CI: 1.36-2.56) to 1.75 (1.27-2.41). The decrease was more pronounced when adjusting for asbestos than for heavy metals or PAH. Analyses by birth cohort suggested an effect of occupational exposures among older men, while due to small number of endpoints, no conclusion could be drawn about the role of occupational exposures in educational inequalities among younger men. Our study revealed that the impact of occupational exposures on socioeconomic inequalities in cancer incidence, rarely studied until now, exists while of modest magnitude

Coffee and tea intake and risk of brain tumors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study

Michaud D.S., Gallo V., Schlehofer B., Tjonneland A., Olsen A., Overvad K., Dahm C.C., Teucher B., Lukanova A., Boeing H., Schutze M., Trichopoulou A., Lagiou P., Kyrozis A., Sacerdote C., Krogh V., Masala G., Tumino R., Mattiello A., Bueno-de-Mesquita H.B., Ros M.M., Peeters P.H., Van Gils C.H., Skeie G., Engeset D., Parr C.L., Ardanaz E., Chirlaque M.D., Dorronsoro M., Sanchez M.J., Arguelles M., Jakszyn P., Nilsson L.M., Melin B.S., Manjer J., Wirfalt E., Khaw K.T., Wareham N., Allen N.E., Key T.J., Romieu I., Vineis P., Riboli E.

Am J Clin Nutr; 2010; 92(5): 1145-1150

Abstract as provided by PubMed

BACKGROUND: In a recent US cohort study, total coffee and tea consumption was inversely associated with risk of glioma, and experimental studies showed that caffeine can slow the invasive growth of glioblastoma. OBJECTIVE: The objective was to examine the relation between coffee and tea intake and the risk of glioma and meningioma in a large European cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Data on coffee and tea intake were collected from men and women recruited into the EPIC cohort study. Over an average of 8.5 y of follow-up, 343 cases of glioma and 245 cases of meningioma were newly diagnosed in 9 countries. We used Cox proportional hazards models to examine the relation between coffee and tea and brain tumors. RESULTS: We observed no associations between coffee, tea, or combined coffee and tea consumption and risk of either type of brain tumor when using quantiles based on country-specific distributions of intake. However, a significant inverse association was observed for glioma risk among those consuming >/=100 mL coffee and tea per day compared with those consuming <100 mL/d (hazard ratio: 0.66; 95% CI: 0.44, 0.97; P = 0.03). The association was slightly stronger in men (hazard ratio: 0.59; 95% CI: 0.34, 1.01) than in women (hazard ratio: 0.74; 95% CI: 0.42, 1.31), although neither was statistically significant. CONCLUSIONS: In this large cohort study, we observed an inverse association between total coffee and tea consumption and risk of glioma that was consistent with the findings of a recent study. These findings, if further replicated in other studies, may provide new avenues of research on gliomas

Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study

Michaud D.S., Gallo V., Schlehofer B., Tjonneland A., Olsen A., Overvad K., Dahm C.C., Kaaks R., Lukanova A., Boeing H., Schutze M., Trichopoulou A., Bamia C., Kyrozis A., Sacerdote C., Agnoli C., Palli D., Tumino R., Mattiello A., Bueno-de-Mesquita H.B., Ros M.M., Peeters P.H., Van Gils C.H., Lund E., Bakken K., Gram I.T., Barricarte A., Navarro C., Dorronsoro M., Sanchez M.J., Rodriguez L., Duell E.J., Hallmans G., Melin B.S., Manjer J., Borgquist S., Khaw K.T., Wareham N., Allen N.E., Tsilidis K.K., Romieu I., Rinaldi S., Vineis P., Riboli E.

Cancer Epidemiol Biomarkers Prev; 2010; 19(10): 2562-2569

Abstract as provided by PubMed

BACKGROUND: The etiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and the risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR, 3.61; 95% CI, 1.75-7.46). CONCLUSION: Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, seems to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation. IMPACT: Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements

Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Nagel G., Linseisen J., Van Gils C.H., Peeters P.H., Boutron-Ruault M.C., Clavel-Chapelon F., Romieu I., Tjonneland A., Olsen A., Roswall N., Witt P.M., Overvad K., Rohrmann S., Kaaks R., Drogan D., Boeing H., Trichopoulou A., Stratigakou V., Zylis D., Engeset D., Lund E., Skeie G., Berrino F., Grioni S., Mattiello A., Masala G., Tumino R., Zanetti R., Ros M.M., Bueno-de-Mesquita H.B., Ardanaz E., Sanchez M.J., Huerta J.M., Amiano P., Rodriguez L., Manjer J., Wirfalt E., Lenner P., Hallmans G., Spencer E.A., Key T.J., Bingham S., Khaw K.T., Rinaldi S., Slimani N., Boffetta P., Gallo V., Norat T., Riboli E.

Breast Cancer Res Treat; 2010; 119(3): 753-765

Abstract as provided by PubMed

So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded

Plasma phytanic acid concentration and risk of prostate cancer: results from the European Prospective Investigation into Cancer and Nutrition

Price A.J., Allen N.E., Appleby P.N., Crowe F.L., Jenab M., Rinaldi S., Slimani N., Kaaks R., Rohrmann S., Boeing H., Pischon T., Benetou V., Naska A., Trichopoulou A., Palli D., Sieri S., Tumino R., Vineis P., Bueno-de-Mesquita H.B., Donate I., Gonzalez C.A., Sanchez M.J., Chirlaque M.D., Ardanaz E., Larranaga N., Khaw K.T., Rodwell S., Gallo V., Michaud D.S., Riboli E., Key T.J.

Am J Clin Nutr; 2010; 91(6): 1769-1776

Abstract as provided by PubMed

BACKGROUND: Phytanic acid, a fatty acid predominantly obtained from foods high in ruminant fat, may have a biological role in the up-regulation of the protein alpha-methylacyl-coenzyme A racemase, which is overexpressed in prostate cancer tissue. OBJECTIVE: This study aimed to examine the association between plasma concentrations of phytanic acid and subsequent risk of prostate cancer. DESIGN: Within the European Prospective Investigation into Cancer and Nutrition cohort, 566 incident prostate cancer cases from Germany, Greece, Italy, the Netherlands, Spain, and the United Kingdom were individually matched to 566 controls by study center, age at recruitment, and time of day and duration of fasting at blood collection. Phytanic acid concentrations were measured by using a gas chromatography-mass spectrometry assay. RESULTS: In controls, plasma phytanic acid concentration was strongly correlated with dairy fat intake (r = 0.49, P < 0.0001), varied significantly by country (P for heterogeneity < 0.0001), and decreased with age (P for trend = 0.02) and duration of fasting at blood collection (P for trend = 0.002). There was no significant association of phytanic acid with prostate cancer risk overall (odds ratio for a doubling in concentration: 1.05; 95% CI: 0.91, 1.21; P for trend = 0.53) or by stage or grade of disease. However, in men who had fasted (>3 h) at blood collection, the odds ratio for prostate cancer was 1.27 (95% CI: 1.01, 1.60; P for trend = 0.04). CONCLUSION: Plasma phytanic acid concentration is significantly associated with intake of dairy fat but not with overall risk of prostate cancer in this European population

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