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Search Result (484 REFERENCES)

2015

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

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

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

PMID:25855626

Abstract as provided by PubMed

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

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

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

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

PMID:25650288

Abstract as provided by PubMed

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

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

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

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

Abstract as provided by PubMed

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

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

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

BMC Med; 2015; 13(1): 107

Abstract as provided by PubMed

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

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

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

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

PMID:25677034

Abstract as provided by PubMed

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

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

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

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

Abstract as provided by PubMed

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

Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort

Schmidt J. A., Rinaldi S., Ferrari P., Carayol M., Achaintre D., Scalbert A., Cross A. J., Gunter M. J., Fensom G. K., Appleby P. N., Key T. J., Travis R. C.

Am J Clin Nutr; 2015; 102(6): 1518-26

PMID:26511225

Abstract as provided by PubMed

BACKGROUND: Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. OBJECTIVE: We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. DESIGN: In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate-controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. RESULTS: Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. CONCLUSIONS: Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans.

Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study

Sen A., Tsilidis K.K., Allen N.E., Rinaldi S., Appleby P.N., Almquist M., Schmidt J.A., Dahm C.C., Overvad K., Tjonneland A., Rostgaard-Hansen A.L., Clavel-Chapelon F., Baglietto L., Boutron-Ruault M.C., Kuhn T., Katze V.A., Boeing H., Trichopoulou A., Tsironis C., Lagiou P., Palli D., Pala V., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita H.A., Peeters P.H., Hjartaker A., Lund E., Weiderpass E., Quiros J.R., Agudo A., Sanchez M.J., Arriola L., Gavrila D., Gurrea A.B., Tosovic A., Hennings J., Sandstrom M., Romieu I., Ferrari P., Zamora-Ros R., Khaw K.T., Wareham N.J., Riboli E., Gunter M., Franceschi S.

Br J Cancer; 2015; 113(5): 840-847

Abstract as provided by PubMed

BACKGROUND: Results from several cohort and case-control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. METHODS: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. RESULTS: Compared with participants consuming 0.1-4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1-1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR=0.77; 95% CI=0.60-0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes. CONCLUSIONS: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas

A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes

Sluijs I., Holmes M.V., van der Schouw Y.T., Beulens J.W., Asselbergs F.W., Huerta J.M., Palmer T.M., Arriola L., Balkau B., Barricarte A., Boeing H., Clavel-Chapelon F., Fagherazzi G., Franks P.W., Gavrila D., Kaaks R., Khaw K.T., Kuhn T., Molina-Montes E., Mortensen L.M., Nilsson P.M., Overvad K., Palli D., Panico S., Quiros J.R., Rolandsson O., Sacerdote C., Sala N., Schmidt J.A., Scott R.A., Sieri S., Slimani N., Spijkerman A.M., Tjonneland A., Travis R.C., Tumino R., van der A.DL, Sharp S.J., Forouhi N.G., Langenberg C., Riboli E., Wareham N.J.

Diabetes; 2015; 64(8): 3028-3036

Abstract as provided by PubMed

We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident case subjects with type 2 diabetes were ascertained. Higher uric acid was associated with a higher diabetes risk after adjustment for confounders, with a hazard ratio (HR) of 1.20 (95% CI 1.11, 1.30) per 59.48 micromol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 micromol/L (95% CI 15, 18) per SD increase and explained 4% of uric acid variation. By using the genetic score to estimate the unconfounded effect, we found that a 59.48 micromol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01 [95% CI 0.87, 1.16]). Including data from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, increasing our dataset to 41,508 case subjects with diabetes, the summary odds ratio estimate was 0.99 (95% CI 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid-lowering therapies may therefore not be beneficial in reducing diabetes risk

General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

Steffen A., Huerta J.M., Weiderpass E., Bueno-de-Mesquita H.B., May A.M., Siersema P.D., Kaaks R., Neamat-Allah J., Pala V., Panico S., Saieva C., Tumino R., Naccarati A., Dorronsoro M., Sanchez-Cantalejo E., Ardanaz E., Quiros J.R., Ohlsson B., Johansson M., Wallner B., Overvad K., Halkjaer J., Tjonneland A., Fagherazzi G., Racine A., Clavel-Chapelon F., Key T.J., Khaw K.T., Wareham N., Lagiou P., Bamia C., Trichopoulou A., Ferrari P., Freisling H., Lu Y., Riboli E., Cross A.J., Gonzalez C.A., Boeing H.

Int. J Cancer; 2015; 137(3): 646-657

PMID:25598323

Abstract as provided by PubMed

General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation

Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

Tikk K., Sookthai D., Fortner R.T., Johnson T., Rinaldi S., Romieu I., Tjonneland A., Olsen A., Overvad K., Clavel-Chapelon F., Baglietto L., Boeing H., Trichopoulou A., Lagiou P., Trichopoulos D., Masala G., Krogh V., Tumino R., Ricceri F., Mattiello A., Agudo A., Menendez V., Sanchez M.J., Amiano P., Chirlaque M.D., Barricarte A., Bueno-de-Mesquita H.B., Monninkhof E.M., Onland-Moret N.C., Andresson A., Sund M., Weiderpass E., Khaw K.T., Key T.J., Travis R.C., Merritt M.A., Riboli E., Dossus L., Kaaks R.

Breast Cancer Res; 2015; 49

PMID:25887963

Abstract as provided by PubMed

INTRODUCTION: The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. METHODS: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. RESULTS: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2=1.35 (95% CI 1.04-1.76), Ptrend=0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet=0.98) or baseline HT use (Phet=0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend=0.06 vs Ptrend=0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors<4 years compared to >/=4 years after blood donation (Ptrend=0.01 vs Ptrend=0.63; Phet=0.04) and among nulliparous women compared to parous women (Ptrend=0.03 vs Ptrend=0.15; Phet=0.07). CONCLUSIONS: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer

Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition

Tsilidis K.K., Allen N.E., Appleby P.N., Rohrmann S., Nothlings U., Arriola L., Gunter M.J., Chajes V., Rinaldi S., Romieu I., Murphy N., Riboli E., Tzoulaki I., Kaaks R., Lukanova A., Boeing H., Pischon T., Dahm C.C., Overvad K., Quiros J.R., Fonseca-Nunes A., Molina-Montes E., Gavrila Chervase D., Ardanaz E., Khaw K.T., Wareham N.J., Roswall N., Tjonneland A., Lagiou P., Trichopoulos D., Trichopoulou A., Palli D., Pala V., Tumino R., Vineis P., Bueno-de-Mesquita H.B., Malm J., Orho-Melander M., Johansson M., Stattin P., Travis R.C., Key T.J.

Int J Cancer; 2015; 136(2): 372-381

PMID:24862312

Abstract as provided by PubMed

The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade of the disease. The association between self-reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow-up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC-participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross-sectional association between circulating concentrations of androgens and insulin-like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63-0.86). There was no evidence that the association differed by stage (p-heterogeneity, 0.19) or grade (p-heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self-reported diabetes mellitus and subsequent risk of prostate cancer

Alcohol consumption and the risk of renal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Wozniak M.B., Brennan P., Brenner D.R., Overvad K., Olsen A., Tjonneland A., Boutron-Ruault M.C., Clavel-Chapelon F., Fagherazzi G., Katzke V., Kuhn T., Boeing H., Bergmann M.M., Steffen A., Naska A., Trichopoulou A., Trichopoulos D., Saieva C., Grioni S., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita H.B., Peeters P.H., Hjartaker A., Weiderpass E., Arriola L., Molina-Montes E., Duell E.J., Santiuste C., Alonso de la Torre, Barricarte Gurrea A., Stocks T., Johansson M., Ljungberg B., Wareham N., Khaw K.T., Travis R.C., Cross A.J., Murphy N., Riboli E., Scelo G.

Int. J Cancer; 2015; 137(8): 1953-1966

PMID:25866035

Abstract as provided by PubMed

Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), 0.91 (0.63-1.30), respectively, (ptrend = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer

Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study

Zamora-Ros R., Rinaldi S., Biessy C., Tjonneland A., Halkjaer J., Fournier A., Boutron-Ruault M.C., Mesrine S., Tikk K., Fortner R.T., Boeing H., Forster J., Trichopoulou A., Trichopoulos D., Papatesta E.M., Masala G., Tagliabue G., Panico S., Tumino R., Polidoro S., Peeters P.H., Bueno-de-Mesquita H.B., Weiderpass E., Lund E., Arguelles M., Agudo A., Molina-Montes E., Navarro C., Barricarte A., Larranaga N., Manjer J., Almquist M., Sandstrom M., Hennings J., Tsilidis K.K., Schmidt J.A., Khaw K.T., Wareham N.J., Romieu I., Byrnes G., Gunter M.J., Riboli E., Franceschi S.

Int J Cancer; 2015; 136(5): 1218-1227

PMID:25041790

Abstract as provided by PubMed

Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for </=5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for >/=9 vs. </=1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR = 1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR = 1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause

2014

Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study

Abbas S., Linseisen J., Rohrmann S., Beulens J.W., Buijsse B., Amiano P., Ardanaz E., Balkau B., Boeing H., Clavel-Chapelon F., Fagherazzi G., Franks P.W., Gavrila D., Grioni S., Kaaks R., Key T.J., Khaw K.T., Kuhn T., Mattiello A., Molina-Montes E., Nilsson P.M., Overvad K., Quiros J.R., Rolandsson O., Sacerdote C., Saieva C., Slimani N., Sluijs I., Spijkerman A.M., Tjonneland A., Tumino R., van der A.DL, Zamora-Ros R., Sharp S.J., Langenberg C., Forouhi N.G., Riboli E., Wareham N.J.

Eur J Clin Nutr; 2014; 68(2): 196-202

Abstract as provided by PubMed

Background/Objectives:Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation.Subjects/Methods:Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N=15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N=2347) were used to calibrate habitual intake data derived from dietary questionnaires.Results:Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (Ptrend=0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mug/day dietary vitamin D.Conclusions:This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person

Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer

Aleksandrova K., Boeing H., Nothlings U., Jenab M., Fedirko V., Kaaks R., Lukanova A., Trichopoulou A., Trichopoulos D., Boffetta P., Trepo E., Westhpal S., Duarte-Salles T., Stepien M., Overvad K., Tjonneland A., Halkjaer J., Boutron-Ruault M.C., Dossus L., Racine A., Lagiou P., Bamia C., Benetou V., Agnoli C., Palli D., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita B., Peeters P.H., Gram I.T., Lund E., Weiderpass E., Quiros J.R., Agudo A., Sanchez M.J., Gavrila D., Barricarte A., Dorronsoro M., Ohlsson B., Lindkvist B., Johansson A., Sund M., Khaw K.T., Wareham N., Travis R.C., Riboli E., Pischon T.

Hepatology; 2014; 60(3): 858-871

Abstract as provided by PubMed

Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n = 125), GBTC (n = 137), or IBD (n = 34). Using risk-set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide, and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95% CI = 1.02-1.46; P = 0.03; 1.90; 95% CI = 1.30-2.77; P = 0.001; 2.25; 95% CI = 1.43-3.54; P = 0.0005; and 2.09; 95% CI = 1.19-3.67; P = 0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95% CI = 1.05-1.42; P = 0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95% CI = 1.25-2.11; P = 0.0003) and IBD (IRR = 10.5; 95% CI = 2.20-50.90; P = 0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. CONCLUSION: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors. (Hepatology 2014;60:858-871)

Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

Aleksandrova K., Jenab M., Bueno-de-Mesquita H.B., Fedirko V., Kaaks R., Lukanova A., van Duijnhoven F.J., Jansen E., Rinaldi S., Romieu I., Ferrari P., Murphy N., Gunter M.J., Riboli E., Westhpal S., Overvad K., Tjonneland A., Halkjaer J., Boutron-Ruault M.C., Dossus L., Racine A., Trichopoulou A., Bamia C., Orfanos P., Agnoli C., Palli D., Panico S., Tumino R., Vineis P., Peeters P.H., Duell E.J., Molina-Montes E., Quiros J.R., Dorronsoro M., Chirlaque M.D., Barricarte A., Ljuslinder I., Palmqvist R., Travis R.C., Khaw K.T., Wareham N., Pischon T., Boeing H.

Eur J Epidemiol; 2014; 29(4): 261-275

Abstract as provided by PubMed

A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development

Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study

Aleksandrova K., Drogan D., Boeing H., Jenab M., Bas Bueno-de-Mesquita H., Jansen E., van Duijnhoven F.J., Rinaldi S., Fedirko V., Romieu I., Kaaks R., Riboli E., Gunter M.J., Romaguera D., Westhpal S., Overvad K., Tjonneland A., Halkjaer J., Boutron-Ruault M.C., Clavel-Chapelon F., Lukanova A., Trichopoulou A., Trichopoulos D., Vidalis P., Panico S., Agnoli C., Palli D., Tumino R., Vineis P., Buckland G., Sanchez-Cruz J.J., Dorronsoro M., Diaz M.J., Barricarte A., Ramon Quiros J., Peeters P.H., May A.M., Hallmans G., Palmqvist R., Crowe F.L., Khaw K.T., Wareham N., Pischon T.

Int J Cancer; 2014; 134(3): 612-621

Abstract as provided by PubMed

Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study

Aleksandrova K., Pischon T., Jenab M., Bueno-De-Mesquita H., Fedirko V., Norat T., Romaguera D., Knuppel S., Boutron-Ruault M.C., Dossus L., Dartois L., Kaaks R., Li K., Tjonneland A., Overvad K., Quiros J., Buckland G., Sanchez M., Dorronsoro M., Chirlaque M.D., Barricarte A., Khaw K.T., Wareham N.J., Bradbury K.E., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Krogh V., Tumino R., Naccarati A., Panico S., Siersema P.D., Peeters P., Ljuslinder I., Johansson I., Ericson U., Ohlsson B., Weiderpass E., Skeie G., Borch K., Rinaldi S., Romieu I., Kong J., Gunter M.J., Ward H.A., Riboli E., Boeing H.

BMC Med; 2014; 12(1): 168

Abstract as provided by PubMed

BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention

Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study

Buckland G., Ros M.M., Roswall N., Bueno-de-Mesquita H.B., Travier N., Tjonneland A., Kiemeney L.A., Sacerdote C., Tumino R., Ljungberg B., Gram I.T., Weiderpass E., Skeie G., Malm J., Ehrnstrom R., Chang-Claude J., Mattiello A., Agnoli C., Peeters P.H., Boutron-Ruault M.C., Fagherazzi G., Clavel-Chapelon F., Nilsson L.M., Amiano P., Trichopoulou A., Oikonomou E., Tsiotas K., Sanchez M.J., Overvad K., Quiros J.R., Chirlaque M.D., Barricarte A., Key T.J., Allen N.E., Khaw K.T., Wareham N., Riboli E., Kaaks R., Boeing H., Palli D., Romieu I., Romaguera D., Gonzalez C.A.

Int J Cancer; 2014; 134(10): 2504-2511

Abstract as provided by PubMed

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers

Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study

Campa D., Mergarten B., De Vivo I, Boutron-Ruault M.C., Racine A., Severi G., Nieters A., Katzke V.A., Trichopoulou A., Yiannakouris N., Trichopoulos D., Boeing H., Quiros J.R., Duell E.J., Molina-Montes E., Huerta J.M., Ardanaz E., Dorronsoro M., Khaw K.T., Wareham N., Travis R.C., Palli D., Pala V., Tumino R., Naccarati A., Panico S., Vineis P., Riboli E., Siddiq A., Bueno-de-Mesquita H.B., Peeters P.H., Nilsson P.M., Sund M., Ye W., Lund E., Jareid M., Weiderpass E., Duarte-Salles T., Kong S.Y., Stepien M., Canzian F., Kaaks R.

Cancer Epidemiol Biomarkers Prev; 2014; 23(11): 2447-2454

Abstract as provided by PubMed

BACKGROUND: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. METHODS: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). RESULTS: We observed that the mean LTL was higher in cases (0.59 +/- 0.20) than in controls (0.57 +/- 0.17), although this difference was not statistically significant (P = 0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk [OR, 1.13; 95% confidence interval (CI), 1.01-1.27]. Additional analyses by cubic spline regression suggested a possible nonlinear relationship between LTL and pancreatic cancer risk (P = 0.022), with a statistically nonsignificant increase in risk at very low LTL, as well as a significant increase at high LTL. CONCLUSION: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. IMPACT: The results of this article can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: evidence from the EPIC cohort

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

Int J Cancer; 2014; 135(2): 440-452

Abstract as provided by PubMed

To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2-2.0) and 1.8 (1.1-2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4-2.4) and 7.4 (2.8-19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9-1.9) and 2.3 (1.3-4.1) for CT seropositivity, and 1.4 (1.0-2.0) and 1.5 (0.9-2.6) for HHV-2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR = 10.2 (3.3-31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non-STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV-2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development

Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer risk

Chuang S.C., Fanidi A., Ueland P.M., Relton C., Midttun O., Vollset S.E., Gunter M.J., Seckl M.J., Travis R.C., Wareham N., Trichopoulou A., Lagiou P., Trichopoulos D., Peeters P.H., Bueno-de-Mesquita H.B., Boeing H., Wientzek A., Kuehn T., Kaaks R., Tumino R., Agnoli C., Palli D., Naccarati A., Aicua E.A., Sanchez M.J., Quiros J.R., Chirlaque M.D., Agudo A., Johansson M., Grankvist K., Boutron-Ruault M.C., Clavel-Chapelon F., Fagherazzi G., Weiderpass E., Riboli E., Brennan P.J., Vineis P., Johansson M.

Cancer Epidemiol Biomarkers Prev; 2014; 23(3): 461-468

Abstract as provided by PubMed

BACKGROUND: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk. RESULTS: Tryptophan (Ptrend = 2 x 10(-5)) and the kynurenine/tryptophan ratio (KTR; Ptrend = 4 x 10(-5)) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th vs. 1st) were 0.52 [95% confidence interval (CI), 0.37-0.74] for tryptophan and 1.74 (95% CI, 1.24-2.45) for KTR. After adjusting for plasma methionine (available from previous work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted Ptrend = 0.13) and KTR (Ptrend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62-4.94, Ptrend = 3 x 10(-5)) that was only marginally affected by adjusting for methionine. CONCLUSIONS: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology. IMPACT: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk

Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European Prospective Investigation into Cancer-Eurgast cohort

Companioni O., Bonet C., Munoz X., Weiderpass E., Panico S., Tumino R., Palli D., Agnoli C., Vineis P., Boutron-Ruault M.C., Racine A., Clavel-Chapelon F., Travis R.C., Khaw K.T., Riboli E., Murphy N., Vergnaud A.C., Trichopoulou A., Benetou V., Trichopoulos D., Lund E., Johansen D., Lindkvist B., Johansson M., Sund M., Ardanaz E., Sanchez-Cantalejo E., Huerta J.M., Dorronsoro M., Ramon Quiros J., Tjonneland A., Mortensen L.M., Overvad K., Chang-Claude J., Rizzato C., Boeing H., de Mesquita H.B., Siersema P., Peeters P.H., Numans M.E., Carneiro F., Licaj I., Freisling H., Sala N., Gonzalez C.A.

Int J Cancer; 2014; 134(1): 92-101

Abstract as provided by PubMed

Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p = 0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p = 0.0003) and CD14 with cardia GC (p = 0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC

Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort

Dossus L., Boutron-Ruault M.C., Kaaks R., Gram I.T., Vilier A., Fervers B., Manjer J., Tjonneland A., Olsen A., Overvad K., Chang-Claude J., Boeing H., Steffen A., Trichopoulou A., Lagiou P., Sarantopoulou M., Palli D., Berrino F., Tumino R., Vineis P., Mattiello A., Bueno-de-Mesquita H.B., van Duijnhoven F.J., Bakker M.F., Peeters P.H., Weiderpass E., Bjerkaas E., Braaten T., Menendez V., Agudo A., Sanchez M.J., Amiano P., Tormo M.J., Barricarte A., Butt S., Khaw K.T., Wareham N., Key T.J., Travis R.C., Rinaldi S., McCormack V., Romieu I., Cox D.G., Norat T., Riboli E., Clavel-Chapelon F.

Int J Cancer; 2014; 134(8): 1871-1888

Abstract as provided by PubMed

Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious

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