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2007

The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European prospective investigation into cancer and nutrition

Vollset S.E., Igland J., Jenab M., Fredriksen A., Meyer K., Eussen S., Gjessing H.K., Ueland P.M., Pera G., Sala N., Agudo A., Capella G., Del Giudice G., Palli D., Boeing H., Weikert C., Bueno-de-Mesquita H.B., Carneiro F., Pala V., Vineis P., Tumino R., Panico S., Berglund G., Manjer J., Stenling R., Hallmans G., Martinez C., Dorronsoro M., Barricarte A., Navarro C., Quiros J.R., Allen N., Key T.J., Bingham S., Linseisen J., Kaaks R., Overvad K., Tjonneland A., Buchner F.L., Peeters P.H., Numans M.E., Clavel-Chapelon F., Boutron-Ruault M.C., Trichopoulou A., Lund E., Slimani N., Ferrari P., Riboli E., Gonzalez C.A.

Cancer Epidemiol Biomarkers Prev; 2007; 16(11): 2416-2424

Abstract as provided by PubMed

Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospective study of blood folate levels and gastric cancer. Gastric cancer cases (n = 247) and controls (n = 631) were matched for study center, age, sex, and time of blood donation. Two common single nucleotide polymorphisms of the MTHFR gene were determined, as were plasma concentrations of folate, cobalamin (vitamin B12), total homocysteine, and methylmalonic acid (cobalamin deficiency marker) in prediagnostic plasma. Risk measures were calculated with conditional logistic regression. Although no relations were observed between plasma folate or total homocysteine concentrations and gastric cancer, we observed a trend toward lower risk of gastric cancer with increasing cobalamin concentrations (odds ratio, 0.79 per SD increase in cobalamin; P = 0.01). Further analyses showed that the inverse association between cobalamin and gastric cancer was confined to cancer cases with low pepsinogen A levels (marker of severe chronic atrophic gastritis) at the time of blood sampling. The 677 C-->T MTHFR polymorphism was not associated with gastric cancer, but we observed an increased risk with the variant genotype of the 1298 A-->C polymorphism (odds ratio, 1.47 for CC versus AA; P = 0.04). In conclusion, we found no evidence of a role of folate in gastric cancer etiology. However, we observed increased gastric cancer risk at low cobalamin levels that was most likely due to compromised cobalamin status in atrophic gastritis preceding gastric cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2416-24)

2006

No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition

Agudo A., Sala N., Pera G., Capella G., Berenguer A., Garcia N., Palli D., Boeing H., Del Giudice G., Saieva C., Carneiro F., Berrino F., Sacerdote C., Tumino R., Panico S., Berglund G., Siman H., Stenling R., Hallmans G., Martinez C., Amiano P., Barricarte A., Navarro C., Quiros J.R., Allen N., Key T., Bingham S., Khaw K.T., Linseisen J., Nagel G., Overvad K., Tjonneland A., Olsen A., Bueno-de-Mesquita H.B., Boshuizen H.C., Peeters P.H., Numans M.E., Clavel-Chapelon F., Boutron-Ruault M.C., Trichopoulou A., Lund E., Blaker H., Jenab M., Ferrari P., Norat T., Riboli E., Gonzalez C.A.

Cancer Epidemiol Biomarkers Prev; 2006; 15(5): 1043-1045
Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition

Agudo A., Sala N., Pera G., Capella G., Berenguer A., Garcia N., Palli D., Boeing H., Del Giudice G., Saieva C., Carneiro F., Berrino F., Sacerdote C., Tumino R., Panico S., Berglund G., Siman H., Stenling R., Hallmans G., Martinez C., Bilbao R., Barricarte A., Navarro C., Quiros J.R., Allen N., Key T., Bingham S., Khaw K.T., Linseisen J., Nagel G., Overvad K., Tjonneland A., Olsen A., Bueno-de-Mesquita H.B., Boshuizen H.C., Peeters P.H., Numans M.E., Clavel-Chapelon F., Boutron-Ruault M.C., Trichopoulou A., Lund E., Offerhaus J., Jenab M., Ferrari P., Norat T., Riboli E., Gonzalez C.A.

Cancer Epidemiol Biomarkers Prev; 2006; 15(12): 2427-2434

Abstract as provided by PubMed

Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C>A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus -3859G>A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis

Reliability of biomarkers of iron status, blood lipids, oxidative stress, vitamin D, C-reactive protein and fructosamine in two Dutch cohorts

Al-Delaimy W.K., Jansen E.H., Peeters P.H., van der Laan J.D., van Noord P.A., Boshuizen H.C., van der Schouw Y.T., Jenab M., Ferrari P., Bueno-de-Mesquita H.B.

Biomarkers; 2006; 11(4): 370-382

Abstract as provided by PubMed

Biomarkers are widely used in epidemiology, yet there are few reliability studies to assess the appropriateness of using these biomarkers for the assessment of exposure-disease relationships. The aim of the study was to assess the reliability of 20 biomarkers in serum collected from two Dutch centres (Utrecht and Bilthoven) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) at two points several years apart. Blood samples were collected from 30 men from Bilthoven and 35 women from Utrecht. Ferritin, total iron, total iron-binding capacity, transferrin saturation, transferrin, C-reactive protein, bilirubin, cholesterol, triglycerides, apo lipoprotein-A, apo lipoprotein-B, high-density lipoproteins, low-density lipoproteins, uric acid, creatinine, reactive oxygen metabolites, the ferric-reducing ability of plasma, protein thiol oxidation, fructosamine, and vitamin D biomarkers in serum were analysed from the blood samples at the two points of time. For all biomarkers, except C-reactive protein, there were no substantial changes in the mean levels over time. Uric acid, ferritin, creatinine, HDL, and apo lipoprotein-B levels consistently showed the highest reliability for men and women (intra-class correlation = 0.69-0.86). Among women, the ferric-reducing ability of plasma, and protein thiol oxidation had poor reliability; and among men iron-related biomarkers (except serum ferritin) had poor reliability. With the exception of a few gender-specific differences, most of the 20 biomarkers performed well and can be considered to have sufficient reliability to be used in future cohort studies

Anthropometry, physical activity, and the risk of pancreatic cancer in the European prospective investigation into cancer and nutrition

Berrington de Gonzalez A., Spencer E.A., Bueno-de-Mesquita H.B., Roddam A., Stolzenberg-Solomon R., Halkjaer J., Tjonneland A., Overvad K., Clavel-Chapelon F., Boutron-Ruault M.C., Boeing H., Pischon T., Linseisen J., Rohrmann S., Trichopoulou A., Benetou V., Papadimitriou A., Pala V., Palli D., Panico S., Tumino R., Vineis P., Boshuizen H.C., Ocke M.C., Peeters P.H., Lund E., Gonzalez C.A., Larranaga N., Martinez-Garcia C., Mendez M., Navarro C., Quiros J.R., Tormo M.J., Hallmans G., Ye W., Bingham S.A., Khaw K.T., Allen N., Key T.J., Jenab M., Norat T., Ferrari P., Riboli E.

Cancer Epidemiol Biomarkers Prev; 2006; 15(5): 879-885

Abstract as provided by PubMed

Tobacco smoking is the only established risk factor for pancreatic cancer. Results from several epidemiologic studies have suggested that increased body mass index and/or lack of physical activity may be associated with an increased risk of this disease. We examined the relationship between anthropometry and physical activity recorded at baseline and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (n = 438,405 males and females age 19-84 years and followed for a total of 2,826,070 person-years). Relative risks (RR) were calculated using Cox proportional hazards models stratified by age, sex, and country and adjusted for smoking and self-reported diabetes and, where appropriate, height. In total, there were 324 incident cases of pancreatic cancer diagnosed in the cohort over an average of 6 years of follow-up. There was evidence that the RR of pancreatic cancer was associated with increased height [RR, 1.74; 95% confidence interval (95% CI), 1.20-2.52] for highest quartile compared with lowest quartile (P(trend) = 0.001). However, this trend was primarily due to a low risk in the lowest quartile, as when this group was excluded, the trend was no longer statistically significant (P = 0.27). A larger waist-to-hip ratio and waist circumference were both associated with an increased risk of developing the disease (RR per 0.1, 1.24; 95% CI, 1.04-1.48; P(trend) = 0.02 and RR per 10 cm, 1.13; 95% CI, 1.01-1.26; P(trend) = 0.03, respectively). There was a nonsignificant increased risk of pancreatic cancer with increasing body mass index (RR, 1.09; 95% CI, 0.95-1.24 per 5 kg/m(2)), and a nonsignificant decreased risk with total physical activity (RR, 0.82; 95% CI, 0.50-1.35 for most active versus inactive). Future studies should consider including measurements of waist and hip circumference, to further investigate the relationship between central adiposity and the risk of pancreatic cancer

Tobacco smoke and bladder cancer--in the European Prospective Investigation into Cancer and Nutrition

Bjerregaard B.K., Raaschou-Nielsen O., Sorensen M., Frederiksen K., Christensen J., Tjonneland A., Overvad K., Chapelon F.C., Nagel G., Chang-Claude J., Bergmann M.M., Boeing H., Trichopoulos D., Trichopoulou A., Oikonomou E., Berrino F., Palli D., Tumino R., Vineis P., Panico S., Peeters P.H., Bueno-de-Mesquita H.B., Kiemeney L., Gram I.T., Braaten T., Lund E., Gonzalez C.A., Berglund G., Allen N., Roddam A., Bingham S., Riboli E.

Int J Cancer; 2006; 119(10): 2412-2416

Abstract as provided by PubMed

The purpose of the present study was to investigate the association between smoking and the development of bladder cancer. The study population consisted of 429,906 persons participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), 633 of whom developed bladder cancer during the follow-up period. An increased risk of bladder cancer was found for both current- (incidence rate ratio 3.96, 95% confidence interval: 3.07-5.09) and ex- (2.25, 1.74-2.91) smokers, compared to never-smokers. A positive association with intensity (per 5 cigarettes) was found among current-smokers (1.18, 1.09-1.28). Associations (per 5 years) were observed for duration (1.14, 1.08-1.21), later age at start (0.75, 0.66-0.85) and longer time since quitting (0.92, 0.86-0.98). Exposure to environmental tobacco smoke (ETS) during childhood increased the risk of bladder cancer (1.38, 1.00-1.90), whereas for ETS exposure as adult no effect was detected. The present study confirms the strong association between smoking and bladder cancer. The indication of a higher risk of bladder cancer for those who start smoking at a young age and for those exposed to ETS during childhood adds to the body of evidence suggesting that children are more sensitive to carcinogens than adults

The effect of occasional smoking on smoking-related cancers : In the European Prospective Investigation into Cancer and Nutrition (EPIC)

Bjerregaard B.K., Raaschou-Nielsen O., Sorensen M., Frederiksen K., Tjonneland A., Rohrmann S., Linseisen J., Bergman M.M., Boeing H., Sieri S., Palli D., Tumino R., Sacerdote C., Bueno-de-Mesquita H.B., Buchner F.L., Gram I.T., Braaten T., Lund E., Hallmans G., Agren A., Riboli E.

Cancer Causes Control; 2006; 17(10): 1305-1309

Abstract as provided by PubMed

OBJECTIVE: Most studies on tobacco smoking have focused on daily-smokers. Occasional smokers, who have never smoked daily, have often been included in the reference group of never-smokers. We have investigated the association between occasional smoking and cancer of the bladder, kidney, pancreas, upper aero-digestive tract and lung. METHODS: The study population consisted of 158,488 persons, who provided information on occasional smoking, within the European Prospective Investigation into Cancer and Nutrition (EPIC), 780 of whom developed a smoking-related cancer. We used Cox proportional hazard model, stratified by gender and country to estimate incidence rate ratios (IRR) for smoking-related cancers. RESULTS: The results suggest that occasional smokers have a higher risk of bladder cancer (IRR: 1.92, 95% confidence interval (CI) 0.93-3.98) and of the major smoking-related cancers combined (IRR: 1.24, 95% CI 0.80-1.94) than true never-smokers. Including occasional smokers in the reference group resulted in a lower risk estimate for former and current smokers. CONCLUSIONS: Occasional smoking should be discouraged

Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study

Canzian F., McKay J.D., Cleveland R.J., Dossus L., Biessy C., Rinaldi S., Landi S., Boillot C., Monnier S., Chajes V., Clavel-Chapelon F., Tehard B., Chang-Claude J., Linseisen J., Lahmann P.H., Pischon T., Trichopoulos D., Trichopoulou A., Zilis D., Palli D., Tumino R., Vineis P., Berrino F., Bueno-de-Mesquita H.B., Van Gils C.H., Peeters P.H.M., Pera G., Ardanaz E., Chirlaque M.D., Quiros J.R., Larranaga N., Martinez-Garcia C., Allen N.E., Key T.J., Bingham S.A., Khaw K.T., Slimani N., Norat T., Riboli E., Kaaks R.

Br J Cancer; 2006; 94(2): 299-307

Abstract as provided by PubMed

Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.British Journal of Cancer (2006) 94, 299-307. doi:10.1038/sj.bjc.6602936 www.bjcancer.com Published online 10 January 2006

A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

Cox D.G., Blanche H., Pearce C.L., Calle E.E., Colditz G.A., Pike M.C., Albanes D., Allen N.E., Amiano P., Berglund G., Boeing H., Buring J., Burtt N., Canzian F., Chanock S., Clavel-Chapelon F., Feigelson H.S., Freedman M., Haiman C.A., Hankinson S.E., Henderson B.E., Hoover R., Hunter D.J., Kaaks R., Kolonel L., Kraft P., Le Marchand L., Lund E., Palli D., Peeters P.H., Riboli E., Stram D.O., Thun M., Tjonneland A., Trichopoulos D., Yeager M.

Breast Cancer Res; 2006; 8(5): R54

Abstract as provided by PubMed

ABSTRACT: INTRODUCTION: Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/or androgen receptor (AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). METHODS: The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships (blocks) across the gene were then identified, and haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts (5,603 breast cancer cases and 7,480 controls). RESULTS: We found no association between any genetic variation (SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed. CONCLUSION: Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer

Fish consumption and breast cancer risk. The European Prospective Investigation into Cancer and Nutrition (EPIC)

Engeset D., Alsaker E., Lund E., Welch A., Khaw K.T., Clavel-Chapelon F., Thiebaut A., Chajes V., Key T.J., Allen N.E., Amiano P., Dorronsoro M., Tjonneland A., Stripp C., Peeters P.H., Van Gils C.H., Chirlaque M.D., Nagel G., Linseisen J., Ocke M.C., Bueno-de-Mesquita H.B., Sacerdote C., Tumino R., Ardanaz E., Sanchez M.J., Panico S., Palli D., Trichopoulou A., Kalapothaki V., Benetou V., Quiros J.R., Agudo A., Overvad K., Bjerregaard L., Wirfalt E., Schulz M., Boeing H., Slimani N., Riboli E.

Int J Cancer; 2006; 119(1): 175-182

Abstract as provided by PubMed

There is current interest in fish consumption and marine omega-3 (n-3) fatty acids and breast cancer risk. Some in vitro and animal studies have suggested an inhibitory effect of marine n-3 fatty acids on breast cancer growth, but the results from epidemiological studies that have examined the association between fish consumption and breast cancer risk in humans are inconsistent. We examined fish consumption and breast cancer risk in 310,671 women aged between 25 and 70 yr at recruitment into the European Prospective Investigation Into Cancer and Nutrition (EPIC). The participants completed a dietary questionnaire between 1992-98 and were followed up for incidence of breast cancer for a median of 6.4 yr. Hazard ratio for breast cancer by intake of total and lean and fatty fish were estimated, stratified by study centre and adjusted for established breast cancer risk factors. During follow-up, 4,776 invasive incident breast cancers were reported. No significant associations between intake of total fish and breast cancer risk were observed, hazard ratio (HR) 1.01 (95% confidence interval [CI] 0.99-1.02; p = 0.28 per 10 g fish/day). When examining lean and fatty fish separately, we found a positive significant association only in the highest quintile for fatty fish (HR 1.13, 95% CI 1.01-1.26), but test for trend was not significant (p = 0.10). No associations with breast cancer risk were observed when the study participants were subdivided by menopausal status. Although the period of follow-up is relatively short, the results provide no evidence for an association between fish intake and breast cancer risk

Physical activity and risk of colon and rectal cancers: the European prospective investigation into cancer and nutrition

Friedenreich C., Norat T., Steindorf K., Boutron-Ruault M.C., Pischon T., Mazuir M., Clavel-Chapelon F., Linseisen J., Boeing H., Bergman M., Johnsen N.F., Tjonneland A., Overvad K., Mendez M., Quiros J.R., Martinez C., Dorronsoro M., Navarro C., Gurrea A.B., Bingham S., Khaw K.T., Allen N., Key T., Trichopoulou A., Trichopoulos D., Orfanou N., Krogh V., Palli D., Tumino R., Panico S., Vineis P., Bueno-de-Mesquita H.B., Peeters P.H., Monninkhof E., Berglund G., Manjer J., Ferrari P., Slimani N., Kaaks R., Riboli E.

Cancer Epidemiol Biomarkers Prev; 2006; 15(12): 2398-2407

Abstract as provided by PubMed

We investigated several aspects of the role of physical activity in colon and rectal cancer etiology that remain unclear in the European Prospective Investigation into Nutrition and Cancer. This cohort of 413,044 men and women had 1,094 cases of colon and 599 cases of rectal cancer diagnosed during an average of 6.4 years of follow-up. We analyzed baseline data on occupational, household, and recreational activity to examine associations by type of activity, tumor subsite, body mass index (BMI), and energy intake. The multivariate hazard ratio for colon cancer was 0.78 [95% confidence interval (95% CI), 0.59-1.03] among the most active participants when compared with the inactive, with evidence of a dose-response effect (P(trend) = 0.04). For right-sided colon tumors, the risk was 0.65 (95% CI, 0.43-1.00) in the highest quartile of activity with evidence of a linear trend (P(trend) = 0.004). Active participants with a BMI under 25 had a risk of 0.63 (95% CI, 0.39-1.01) for colon cancer compared with the inactive. Finally, an interaction between BMI and activity (P(interaction) = 0.03) was observed for right-sided colon cancers; among moderately active and active participants with a BMI under 25, a risk of 0.38 (95% CI, 0.21-0.68) was found as compared with inactive participants with BMI >30. No comparable decreased risks were observed for rectal cancer for any type of physical activity for any subgroup analyses or interactions considered. We found that physical activity reduced colon cancer risk, specifically for right-sided tumors and for lean participants, but not rectal cancer

Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC)

Gonzalez Carlos A., Jakszyn Paula, Pera Guillem, Agudo Antonio, Bingham Sheila, Palli Domenico, Ferrari Pietro, Boeing Heiner, del Giudice Giuseppe, Plebani Mario, Carneiro Fatima, Nesi Gabriella, Berrino Franco, Sacerdote Carlotta, Tumino Rosario, Panico Salvatore, Berglund Goran, Siman Henrik, Nyren Olof, Hallmans Goran, Martinez Carmen, Dorronsoro Miren, Barricarte Aurelio, Navarro Carmen, Quiros Jose R., Allen Naomi, Key Timothy J., Day Nicholas E., Linseisen Jakob, Nagel Gabriele, Bergmann Manuela M., Overvad Kim, Jensen Majken K., Tjonneland Anne, Olsen Anja, Bueno-De-Mesquita H.Bas, Ocke Marga, Peeters Petra H.M., Numans Mattijs E., Clavel-Chapelon Francoise, Boutron-Ruault Marie Christine, Trichopoulou Antonia, Psaltopoulou Theodora, Roukos Dimitrios, Lund Eiliv, Hemon Bertrand, Kaaks Rudolf, Norat Teresa, Riboli Elio

J Natl Cancer Inst; 2006; 98(5): 345-354

Abstract as provided by PubMed

BACKGROUND: Dietary factors are thought to have an important role in gastric and esophageal carcinogenesis, but evidence from cohort studies for such a role is lacking. We examined the risks of gastric cancer and esophageal adenocarcinoma associated with meat consumption within the European Prospective Investigation Into Cancer and Nutrition (EPIC) cohort. METHODS: A total of 521,457 men and women aged 35-70 years in 10 European countries participated in the EPIC cohort. Dietary and lifestyle information was collected at recruitment. Cox proportional hazard models were used to examine associations between meat intake and risks of cardia and gastric non-cardia cancers and esophageal adenocarcinoma. Data from a calibration substudy were used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. In a nested case-control study, we examined interactions between Helicobacter pylori infection status (i.e., plasma H. pylori antibodies) and meat intakes. All statistical tests were two-sided. RESULTS: During a mean follow-up of 6.5 years, 330 gastric adenocarcinoma and 65 esophageal adenocarcinomas were diagnosed. Gastric non-cardia cancer risk was statistically significantly associated with intakes of total meat (calibrated HR per 100-g/day increase = 3.52; 95% CI = 1.96 to 6.34), red meat (calibrated HR per 50-g/day increase = 1.73; 95% CI = 1.03 to 2.88), and processed meat (calibrated HR per 50-g/day increase = 2.45; 95% CI = 1.43 to 4.21). The association between the risk of gastric non-cardia cancer and total meat intake was especially large in H. pylori-infected subjects (odds ratio per 100-g/day increase = 5.32; 95% CI = 2.10 to 13.4). Intakes of total, red, or processed meat were not associated with the risk of gastric cardia cancer. A positive but non-statistically significant association was observed between esophageal adenocarcinoma cancer risk and total and processed meat intake in the calibrated model. In this study population, the absolute risk of development of gastric adenocarcinoma within 10 years for a study subject aged 60 years was 0.26% for the lowest quartile of total meat intake and 0.33% for the highest quartile of total meat intake. CONCLUSION: Total, red, and processed meat intakes were associated with an increased risk of gastric non-cardia cancer, especially in H. pylori antibody-positive subjects, but not with cardia gastric cancer

Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Gonzalez C.A., Pera G., Agudo A., Bueno-de-Mesquita H.B., Ceroti M., Boeing H., Schulz M., Del Giudice G., Plebani M., Carneiro F., Berrino F., Sacerdote C., Tumino R., Panico S., Berglund G., Siman H., Hallmans G., Stenling R., Martinez C., Dorronsoro M., Barricarte A., Navarro C., Quiros J.R., Allen N., Key T.J., Bingham S., Day N.E., Linseisen J., Nagel G., Overvad K., Jensen M.K., Olsen A., Tjonneland A., Buchner F.L., Peeters P.H., Numans M.E., Clavel-Chapelon F., Boutron-Ruault M.C., Roukos D., Trichopoulou A., Psaltopoulou T., Lund E., Casagrande C., Slimani N., Jenab M., Riboli E.

Int J Cancer; 2006; 118(10): 2559-2566

Abstract as provided by PubMed

It is considered that fruit and vegetable (F&V) protect against oesophagus and gastric cancer (GC). However, 2 recent meta-analyses suggest that the strength of association on GC seems to be weaker for vegetables than for fruit and weaker in cohort than in case-control studies. No evidence exists from cohort studies about adenocarcinoma of oesophagus (ACO). In 521,457 men and women participating in the EPIC cohort in 10 European countries, information of diet and lifestyle was collected at baseline. After an average of 6.5 years of follow-up, a total of 330 GC and 65 ACO, confirmed and classified by a panel of pathologists, was used for the analysis. We examined the relation between F&V intake and GC and ACO. A calibration study in a sub-sample was used to control diet measurement errors. In a sub-sample of cases and a random sample of controls, antibodies against Helicobacter pylori (Hp) were measured and interactions with F&V were examined in a nested case-control study. We observed no association with total vegetable intake or specific groups of vegetables and GC risk, except for the intestinal type, where a negative association is possible regarding total vegetable (calibrated HR 0.66; 95% CI 0.35-1.22 per 100 g increase) and onion and garlic intake (calibrated HR 0.70; 95% CI 0.38-1.29 per 10 g increase). No evidence of association between fresh fruit intake and GC risk was observed. We found a negative but non significant association between citrus fruit intake and the cardia site (calibrated HR 0.77; 95% CI 0.47-1.22 per 100 g increase) while no association was observed with the non-cardia site. Regarding ACO, we found a non significant negative association for vegetable intake and for citrus intake (calibrated HRs 0.72; 95% CI 0.32-1.64 and 0.77; 95% CI 0.46-1.28 per 100 and 50 g increase, respectively). It seems that Hp infection does not modify the effect of F&V intake. Our study supports a possible protective role of vegetable intake in the intestinal type of GC and the ACO. Citrus fruit consumption may have a role in the protection against cardia GC and ACO

TP53 and KRAS2 mutations in plasma DNA of healthy subjects and subsequent cancer occurrence: a prospective study

Gormally E., Vineis P., Matullo G., Veglia F., Caboux E., Le Roux E., Peluso M., Garte S., Guarrera S., Munnia A., Airoldi L., Autrup H., Malaveille C., Dunning A., Overvad K., Tjonneland A., Lund E., Clavel-Chapelon F., Boeing H., Trichopoulou A., Palli D., Krogh V., Tumino R., Panico S., Bueno-de-Mesquita H.B., Peeters P.H., Pera G., Martinez C., Dorronsoro M., Barricarte A., Navarro C., Quiros J.R., Hallmans G., Day N.E., Key T.J., Saracci R., Kaaks R., Riboli E., Hainaut P.

Cancer Res; 2006; 66(13): 6871-6876

Abstract as provided by PubMed

In cancer patients, plasma often contains mutant DNA released by cancer cells. We have assessed the significance of plasma DNA mutations for subsequent cancer development in healthy subjects in a large longitudinal prospective study. The European Prospective Investigation into Cancer and Nutrition study was analyzed with a nested case-control design. Cases were nonsmokers or ex-smokers for >10 years and newly diagnosed with lung, bladder, or upper aerodigestive tract cancers or leukemia accrued after a median follow-up of 6.3 years. Controls were matched 2:1 for follow-up, age, sex, area of recruitment, and smoking status. KRAS2 mutations were detected by mutant-enriched PCR and sequencing (n = 1,098). TP53 mutations were detected by denaturing high-performance liquid chromatography, temporal temperature gradient electrophoresis, and sequencing (n = 550). KRAS2 or TP53 mutations were detected in 13 of 1,098 (1.2%) and 20 of 550 (3.6%) subjects, respectively, 16 of whom developed cancer on average after 18.3 months of follow-up. Among 137 subjects who developed bladder cancer, 5 had KRAS2 mutations [odds ratio (OR), 4.25; 95% confidence interval (95% CI), 1.27-14.15] and 7 had TP53 mutations (OR, 1.81; 95% CI, 0.66-4.97). There was a nonsignificant trend for association between TP53 mutations and bulky adducts in lymphocyte DNA (OR, 2.78; 95% CI, 0.64-12.17). This is the first report of TP53 or KRAS2 mutations in the plasma of healthy subjects in a prospective study, suggesting that KRAS2 mutation is detectable ahead of bladder cancer diagnosis. TP53 mutation may be associated with environmental exposures. These observations have implications for monitoring early steps of carcinogenesis

Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study

Jakszyn P., Bingham S., Pera G., Agudo A., Luben R., Welch A., Boeing H., Del Giudice G., Palli D., Saieva C., Krogh V., Sacerdote C., Tumino R., Panico S., Berglund G., Siman H., Hallmans G., Sanchez M.J., Larranaga N., Barricarte A., Chirlaque M.D., Quiros J.R., Key T.J., Allen N., Lund E., Carneiro F., Linseisen J., Nagel G., Overvad K., Tjonneland A., Olsen A., Bueno-de-Mesquita H.B., Ocke M.O., Peeters P.H., Numans M.E., Clavel-Chapelon F., Trichopoulou A., Fenger C., Stenling R., Ferrari P., Jenab M., Norat T., Riboli E., Gonzalez C.A.

Carcinogenesis; 2006; 27(7): 1497-1501

Abstract as provided by PubMed

The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521 457 individuals and 314 incident cases of GC that had occurred after 6.6 average years of follow-up. An index of endogenous NOC (ENOC) formation was estimated using data of the iron content from meat intake and faecal apparent total NOC formation according to previous published studies. Antibodies to Helicobacter pylori and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. Exposure to NDMA was <1 mug on average compared with 93 mug on average from ENOC. There was no association between NDMA intake and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40 mug/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although the number of not infected cases is low, our data suggest a possible interaction between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC formation may account for our previously reported association between red and processed meat consumption and gastric cancer risk

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

Jenab M., Riboli E., Ferrari P., Friesen M., Sabate J., Norat T., Slimani N., Tjonneland A., Olsen A., Overvad K., Boutron-Ruault M.C., Clavel-Chapelon F., Boeing H., Schulz M., Linseisen J., Nagel G., Trichopoulou A., Naska A., Oikonomou E., Berrino F., Panico S., Palli D., Sacerdote C., Tumino R., Peeters P.H., Numans M.E., Bueno-de-Mesquita H.B., Buchner F.L., Lund E., Pera G., Chirlaque M.D., Sanchez M.J., Arriola L., Barricarte A., Quiros J.R., Johansson I., Johansson A., Berglund G., Bingham S., Khaw K.T., Allen N., Key T., Carneiro F., Save V., Giudice G.D., Plebani M., Kaaks R., Gonzalez C.A.

Br J Cancer; 2006; 95(3): 406-415

Abstract as provided by PubMed

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30-0.94, P(trend)=0.006), zeaxanthin (OR=0.39, 95% CI=0.22-0.69, P(trend)=0.005), retinol (OR=0.55, 95% CI=0.33-0.93, P(trend)=0.005) and lipid-unadjusted alpha-tocopherol (OR=0.59, 95% CI=0.37-0.94, P(trend)=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR=0.26, 95% CI=0.11-0.65, P(trend)=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.British Journal of Cancer (2006) 95, 406-415. doi:10.1038/sj.bjc.6603266 www.bjcancer.com Published online 11 July 2006

Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Jenab M., Riboli E., Ferrari P., Sabate J., Slimani N., Norat T., Friesen M., Tjonneland A., Olsen A., Overvad K., Boutron-Ruault M.C., Clavel-Chapelon F., Touvier M., Boeing H., Schulz M., Linseisen J., Nagel G., Trichopoulou A., Naska A., Oikonomou E., Krogh V., Panico S., Masala G., Sacerdote C., Tumino R., Peeters P.H., Numans M.E., Bueno-de-Mesquita H.B., Buchner F.L., Lund E., Pera G., Sanchez C.N., Sanchez M.J., Arriola L., Barricarte A., Quiros J.R., Hallmans G., Stenling R., Berglund G., Bingham S., Khaw K.T., Key T., Allen N., Carneiro F., Mahlke U., Del Giudice G., Palli D., Kaaks R., Gonzalez C.A.

Carcinogenesis; 2006; 27(11): 2250-2257

Abstract as provided by PubMed

Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies but data from prospective studies is limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls=416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori (Hp) infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C (OR=0.55, 95%CI=0.31-0.97, Ptrend=0.043) which was maintained after exclusion of cases with </=2yrs follow-up (OR=0.40, 95%CI=0.19-0.83, Ptrend=0.064). The inverse association was more pronounced in subjects consuming higher levels of red and processed meats, a factor that may increase endogenous N-nitroso compound production. The effect of plasma vitamin C was not different by GC anatomical sub-site (cardia/non-cardia) or histological sub-type (diffuse/intestinal) and there was no significant interaction of effect with Hp. The results of this study show, in a prospective setting, an inverse association of GC risk with high levels of plasma vitamin C and suggest an interaction with the intake of red and processed meats, whose consumption may elevate endogenous N-nitroso compound production

Consumption and portion sizes of tree nuts, peanuts and seeds in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries

Jenab M., Sabate J., Slimani N., Ferrari P., Mazuir M., Casagrande C., Deharveng G., Tjonneland A., Olsen A., Overvad K., Boutron-Ruault M.C., Clavel-Chapelon F., Boeing H., Weikert C., Linseisen J., Rohrmann S., Trichopoulou A., Naska A., Palli D., Sacerdote C., Tumino R., Mattiello A., Pala V., Bueno-de-Mesquita H.B., Ocke M.C., Peeters P.H., Engeset D., Skeie G., Jakszyn P., Ardanaz E., Quiros J.R., Chirlaque M.D., Martinez C., Amiano P., Berglund G., Palmqvist R., Guelpen B., Bingham S., Key T., Riboli E.

Br J Nutr; 2006; S12-S23

Abstract as provided by PubMed

Tree nuts, peanuts and seeds are nutrient dense foods whose intake has been shown to be associated with reduced risk of some chronic diseases. They are regularly consumed in European diets either as whole, in spreads or from hidden sources (e.g. commercial products). However, little is known about their intake profiles or differences in consumption between European countries or geographic regions. The objective of this study was to analyse the population mean intake and average portion sizes in subjects reporting intake of nuts and seeds consumed as whole, derived from hidden sources or from spreads. Data was obtained from standardised 24-hour dietary recalls collected from 36 994 subjects in 10 different countries that are part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Overall, for nuts and seeds consumed as whole, the percentage of subjects reporting intake on the day of the recall was: tree nuts=4. 4%, peanuts=2.3 % and seeds=1.3 %. The data show a clear northern (Sweden: mean intake=0.15 g/d, average portion size=15.1 g/d) to southern (Spain: mean intake=2.99 g/d, average portion size=34.7 g/d) European gradient of whole tree nut intake. The three most popular tree nuts were walnuts, almonds and hazelnuts, respectively. In general, tree nuts were more widely consumed than peanuts or seeds. In subjects reporting intake, men consumed a significantly higher average portion size of tree nuts (28.5 v. 23.1 g/d, P<0.01) and peanuts (46.1 v. 35.1 g/d, P<0.01) per day than women. These data may be useful in devising research initiatives and health policy strategies based on the intake of this food group

Dietary intake of different types and characteristics of processed meat which might be associated with cancer risk--results from the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Linseisen J., Rohrmann S., Norat T., Gonzalez C.A., Dorronsoro Iraeta M., Morote Gomez P., Chirlaque M.D., Pozo B.G., Ardanaz E., Mattisson I., Pettersson U., Palmqvist R., Van Guelpen B., Bingham S.A., McTaggart A., Spencer E.A., Overvad K., Tjonneland A., Stripp C., Clavel-Chapelon F., Kesse E., Boeing H., Klipstein-Grobusch K., Trichopoulou A., Vasilopoulou E., Bellos G., Pala V., Masala G., Tumino R., Sacerdote C., Del Pezzo M., Bueno-de-Mesquita H.B., Ocke M.C., Peeters P.H., Engeset D., Skeie G., Slimani N., Riboli E.

Public Health Nutr; 2006; 9(4): 449-464

Abstract as provided by PubMed

OBJECTIVE: There is increasing evidence for a significant effect of processed meat (PM) intake on cancer risk. However, refined knowledge on how components of this heterogeneous food group are associated with cancer risk is still missing. Here, actual data on the intake of PM subcategories is given; within a food-based approach we considered preservation methods, cooking methods and nutrient content for stratification, in order to address most of the aetiologically relevant hypotheses. DESIGN AND SETTING: Standardised computerised 24-hour diet recall interviews were collected within the framework of the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study in 27 centres across 10 European countries. SUBJECTS: Subjects were 22,924 women and 13,031 men aged 35-74 years. RESULTS: Except for the so-called 'health-conscious' cohort in the UK, energy-adjusted total PM intake ranged between 11.1 and 47.9 g day(-1) in women and 18.8 and 88.5 g day(-1) in men. Ham, salami-type sausages and heated sausages contributed most to the overall PM intake. The intake of cured (addition of nitrate/nitrite) PM was highest in the German, Dutch and northern European EPIC centres, with up to 68.8 g day(-1) in men. The same was true for smoked PM (up to 51.8 g day(-1)). However, due to the different manufacturing practice, the highest average intake of NaNO2 through PM consumption was found for the Spanish centres (5.4 mg day(-1) in men) as compared with German and British centres. Spanish centres also showed the highest intake of NaCl-rich types of PM; most cholesterol- and iron-rich PM was consumed in central and northern European centres. Possibly hazardous cooking methods were more often used for PM preparation in central and northern European centres. CONCLUSIONS: We applied a food-based categorisation of PM that addresses aetiologically relevant mechanisms for cancer development and found distinct differences in dietary intake of these categories of PM across European cohorts. This predisposes EPIC to further investigate the role of PM in cancer aetiology

Associations between dietary pattern and lifestyle, anthropometry and other health indicators in the elderly participants of the EPIC-Italy cohort

Pala Valeria, Sieri Sabina, Masala Giovanna, Palli Domenico, Panico Salvatore, Vineis Paolo, Sacerdote Carlotta, Mattiello Amalia, Galasso Rocco, Salvini Simonetta, Ceroti Marco, Berrino Franco, Fusconi Elisabetta, Tumino Rosario, Frasca Graziella, Riboli Elio, Trichopoulou Antonia, Baibas Nikolaos, Krogh Vittorio

Nutr Metab Cardiovasc Dis; 2006; 16(3): 186-201

Abstract as provided by PubMed

INTRODUCTION: Epidemiological studies have shown that dietary behaviour is an important aetiological factor in various chronic diseases. We used principal component factor analysis to identify dietary patterns and to examine the associations of these patterns with health-related variables in a sample of elderly (>/=60years) Italians participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS AND RESULTS: Exploratory factor analysis was applied to the intake of food groups as estimated by semi-quantitative food questionnaires. Individual participants were assigned factor scores, indicating the extent to which their diet conformed to each of the four dietary patterns identified: prudent (cooked vegetables, pulses, cabbage, seed oil and fish); pasta & meat (pasta, tomato sauce, red meat, processed meat, bread and wine); olive oil & salad (raw vegetables, olive oil, soup and chicken); and sweet & dairy (sugar, cakes, ice cream, coffee and dairy). Highly educated people had high scores on prudent and low scores on pasta & meat. The pasta & meat and prudent patterns were strongly positively associated with body mass index (BMI) and waist-to-hip ratio (WHR) in men and women. Hyperlipidaemic men and women consumed more of the prudent and olive oil & salad patterns and less of the sweet & dairy pattern than those with normal lipids. The olive oil & salad was significantly higher and the pasta & meat and sweet & dairy patterns significantly lower in men and women who had dieted over the previous year, suggesting awareness of the health consequences of these patterns. CONCLUSIONS: Dietary pattern analysis provides a characterization of recurrent dietary behaviour in elderly people, and can be used to provide tangible dietary advice to elderly people

Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Pischon T., Lahmann P.H., Boeing H., Tjonneland A., Halkjaer J., Overvad K., Klipstein-Grobusch K., Linseisen J., Becker N., Trichopoulou A., Benetou V., Trichopoulos D., Sieri S., Palli D., Tumino R., Vineis P., Panico S., Monninkhof E., Peeters P.H., Bueno-de-Mesquita H.B., Buchner F.L., Ljungberg B., Hallmans G., Berglund G., Gonzalez C.A., Dorronsoro M., Gurrea A.B., Navarro C., Martinez C., Quiros J.R., Roddam A., Allen N., Bingham S., Khaw K.T., Kaaks R., Norat T., Slimani N., Riboli E.

Int J Cancer; 2006; 118(3): 728-738

Abstract as provided by PubMed

Previous studies suggest that obesity is related to increased risk of renal cell carcinoma (RCC); however, only a few studies report on measures of central vs. peripheral adiposity. We examined the association between anthropometric measures, including waist and hip circumference and RCC risk among 348,550 men and women free of cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 6.0 years of follow-up we identified 287 incident cases of RCC. Relative risks were calculated using Cox regression, stratified by age and study center and adjusted for smoking status, education, alcohol consumption, physical activity, menopausal status, and hormone replacement therapy use. Among women, an increased risk of RCC was conferred by body weight (relative risk [RR] in highest vs. lowest quintile = 2.13; 95% confidence interval [CI] = 1.16-3.90; p-trend = 0.003), body mass index (BMI) (RR = 2.25; 95% CI = 1.14-4.44; p-trend = 0.009), and waist (RR = 1.67; 95% CI = 0.94-2.98; p-trend = 0.003) and hip circumference (RR = 2.30; 95% CI = 1.22-4.34; p-trend = 0.01); however, waist and hip circumference were no longer significant after controlling for body weight. Among men, hip circumference (RR = 0.44; 95% CI = 0.20-0.98; p-trend = 0.03) was related significantly to decreased RCC risk only after accounting for body weight. Height was not related significantly to RCC risk. Our findings suggest that obesity is related to increased risk of RCC irrespective of fat distribution among women, whereas low hip circumference is related to increased RCC risk among men. Our data give further credence to public health efforts aiming to reduce the prevalence of obesity to prevent RCC, in addition to other chronic diseases. (c) 2005 Wiley-Liss, Inc

Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC)

Pischon T., Lahmann P.H., Boeing H., Friedenreich C., Norat T., Tjonneland A., Halkjaer J., Overvad K., Clavel-Chapelon F., Boutron-Ruault M.C., Guernec G., Bergmann M.M., Linseisen J., Becker N., Trichopoulou A., Trichopoulos D., Sieri S., Palli D., Tumino R., Vineis P., Panico S., Peeters P.H., Bueno-de-Mesquita H.B., Boshuizen H.C., Van Guelpen B., Palmqvist R., Berglund G., Gonzalez C.A., Dorronsoro M., Barricarte A., Navarro C., Martinez C., Quiros J.R., Roddam A., Allen N., Bingham S., Khaw K.T., Ferrari P., Kaaks R., Slimani N., Riboli E.

J Natl Cancer Inst; 2006; 98(13): 920-931

Abstract as provided by PubMed

BACKGROUND: Body weight and body mass index (BMI) are positively related to risk of colon cancer in men, whereas weak or no associations exist in women. This discrepancy may be related to differences in fat distribution between sexes or to the use of hormone replacement therapy (HRT) in women. METHODS: We used multivariable adjusted Cox proportional hazards models to examine the association between anthropometric measures and risks of colon and rectal cancer among 368 277 men and women who were free of cancer at baseline from nine countries of the European Prospective Investigation Into Cancer and Nutrition. All statistical tests were two-sided. RESULTS: During 6.1 years of follow-up, we identified 984 and 586 patients with colon and rectal cancer, respectively. Body weight and BMI were statistically significantly associated with colon cancer risk in men (highest versus lowest quintile of BMI, relative risk [RR] = 1.55, 95% confidence interval [CI] = 1.12 to 2.15; P(trend) = .006) but not in women. In contrast, comparisons of the highest to the lowest quintile showed that several anthropometric measures, including waist circumference (men, RR = 1.39, 95% CI = 1.01 to 1.93; P(trend) = .001; women, RR = 1.48, 95% CI = 1.08 to 2.03; P(trend) = .008), waist-to-hip ratio (WHR; men, RR = 1.51, 95% CI = 1.06 to 2.15; P(trend) = .006; women, RR = 1.52, 95% CI = 1.12 to 2.05; P(trend) = .002), and height (men, RR = 1.40, 95% CI = 0.99 to 1.98; P(trend) = .04; women, RR = 1.79, 95% CI = 1.30 to 2.46; P(trend)<.001) were related to colon cancer risk in both sexes. The estimated absolute risk of developing colon cancer within 5 years was 203 and 131 cases per 100,000 men and 129 and 86 cases per 100,000 women in the highest and lowest quintiles of WHR, respectively. Upon further stratification, no association of waist circumference and WHR with risk of colon cancer was observed among postmenopausal women who used HRT. None of the anthropometric measures was statistically significantly related to rectal cancer. CONCLUSIONS: Waist circumference and WHR, indicators of abdominal obesity, were strongly associated with colon cancer risk in men and women in this population. The association of abdominal obesity with colon cancer risk may vary depending on HRT use in postmenopausal women; however, these findings require confirmation in future studies

Breast cancer risk in relation to abortion: Results from the EPIC study

Reeves G.K., Kan S.W., Key T., Tjonneland A., Olsen A., Overvad K., Peeters P.H., Clavel-Chapelon F., Paoletti X., Berrino F., Krogh V., Palli D., Tumino R., Panico S., Vineis P., Gonzalez C.A., Ardanaz E., Martinez C., Amiano P., Quiros J.R., Tormo M.R., Khaw K.T., Trichopoulou A., Psaltopoulou T., Kalapothaki V., Nagel G., Chang-Claude J., Boeing H., Lahmann P.H., Wirfalt E., Kaaks R., Riboli E.

Int J Cancer; 2006; 119(7): 1741-1745

Abstract as provided by PubMed

The role of spontaneous and induced abortion on breast cancer risk is examined among 267,361 women recruited into the European Prospective Investigation into Cancer and nutrition between 1992 and 2000. The data were collected from 20 centers, across 9 countries, and included information on a total of 4,805 women with breast cancer, of whom 1,657 reported having ever had any type of abortion. Overall, the relative risk of breast cancer in women who reported ever having had a spontaneous abortion was not significantly elevated when compared with women who reported never having had such an abortion (RR = 1.07, 95% CI = 0.99-1.14). However, there was some evidence of a slight increase in the risk of breast cancer among women who reported having had 2 or more spontaneous abortions (1.20, 1.07-1.35). The relative risk of breast cancer among women who reported ever having had an induced abortion when compared to women who reported never having had an induced abortion was 0.95 (0.87-1.03). Overall, the findings provide further unbiased evidence of the lack of an adverse effect of induced abortion on breast cancer risk

IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC)

Rinaldi S., Peeters P.H., Berrino F., Dossus L., Biessy C., Olsen A., Tjonneland A., Overvad K., Clavel-Chapelon F., Boutron-Ruault M.C., Tehard B., Nagel G., Linseisen J., Boeing H., Lahmann P.H., Trichopoulou A., Trichopoulos D., Koliva M., Palli D., Panico S., Tumino R., Sacerdote C., Van Gils C.H., van Noord P., Grobbee D.E., Bueno-de-Mesquita H.B., Gonzalez C.A., Agudo A., Chirlaque M.D., Barricarte A., Larranaga N., Quiros J.R., Bingham S., Khaw K.T., Key T., Allen N.E., Lukanova A., Slimani N., Saracci R., Riboli E., Kaaks R.

Endocr Relat Cancer; 2006; 13(2): 593-605

Abstract as provided by PubMed

Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02-1.86), P = 0.01, and 1.44 (95% CI 1.04-1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60-1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50-1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57-1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19-1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women

Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition

Rinaldi S., Peeters P.H., Bezemer I.D., Dossus L., Biessy C., Sacerdote C., Berrino F., Panico S., Palli D., Tumino R., Khaw K.T., Bingham S., Allen N.E., Key T., Jensen M.K., Overvad K., Olsen A., Tjonneland A., Amiano P., Ardanaz E., Agudo A., Martinez-Garcia C., Quiros J.R., Tormo M.J., Nagel G., Linseisen J., Boeing H., Schulz M., Grobbee D.E., Bueno-de-Mesquita H.B., Koliva M., Kyriazi G., Thrichopoulou A., Boutron-Ruault M.C., Clavel-Chapelon F., Ferrari P., Slimani N., Saracci R., Riboli E., Kaaks R.

Cancer Causes Control; 2006; 17(8): 1033-1043

Abstract as provided by PubMed

OBJECTIVE: Women with a moderate intake of alcohol have higher concentrations of sex steroids in serum, and higher risk of developing breast cancer, compared to non-drinkers. In the present study, we investigate the relationships between alcohol consumption and serum levels of sex steroids and sex-hormone binding globulin (SHBG) in 790 pre- and 1,291 post-menopausal women, who were part of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Serum levels of testosterone (T), androstenedione (Delta(4)), dehydroepiandrosterone sulphate (DHEAS), estrone (E(1)), estradiol (E(2)) and SHBG were measured by direct immunoassays. Free T (fT) and free E(2) (fE(2)) were calculated according to mass action laws. Current alcohol intake exposure to alcohol was assessed from dietary questionnaires. RESULTS: Pre-menopausal women who consumed more than 25 g/day of alcohol had about 30% higher DHEAS, T and fT, 20% higher Delta(4) and about 40% higher E(1), concentrations compared to women who were non-consumers. E(2), fE(2) and SHBG concentrations showed no association with current alcohol intake. In post-menopausal women, DHEAS, fT, T, Delta(4), and E(1) concentrations were between 10% and 20% higher in women who consumed more than 25 g/day of alcohol compared to non-consumers. E(2) or fE(2) were not associated with alcohol intake at all. SHBG levels were about 15% lower in alcohol consumers compared to non-consumers. CONCLUSION: This study supports the hypothesis of an influence of alcohol intake on sex hormone concentrations in blood

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