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BACKGROUND: Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. METHODS: Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28,114 women with and 94,942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. FINDINGS: After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1·06, 95% CI 1·01-1·11, p=0·01). Of 17,641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables. What's new? Previous studies have clearly shown dose-response relationships between tobacco/alcohol use and the risk of upper-aerodigestive- tract (UADT) cancers, but these studies have focused only on the variables of frequency and duration of use. In this study, the authors asked whether addiction to smoking might be an independent risk factor. They found that addiction was indeed associated with UADT cancer risk among current smokers. This addiction-cancer association suggests that it is important to include questions that elicit information regarding smoking addiction when accounting for smoking effect through questionnaire information. Copyright © 2013 UICC.

Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR 5 2.50; 95% CI 5 2.02-3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR 5 1.61; 95% CI 5 1.13-2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels. © 2014 UICC.

Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with

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Background: Data on colorectal cancer (CRC) in HIV-positive patients are limited. The study objective was to investigate and compare clinical presentation and outcome between HIV-positive and HIV-negative CRC patients. Patients and Methods: Between September 1985 and November 2003 we identified 27 cases of HIV-positive CRC patients from the cancer registry database-Italian Cooperative Group AIDS and Tumours (GICAT); the clinical presentation/outcome information was retrieved. Each HIV-positive patient from our institution was randomly matched (ratio 1: 2) with HIV-negative patients (54 controls) based on age, sex, and year of diagnosis in the same time period. Differences in clinical presentation, treatment, and overall survival were assessed. Results: Of 1130 HIV-negative CRC patients, 54 were identified and matched with 27 HIV-positive patients. Compared with the HIV-negative patients, the HIV-positive patients had a higher risk of lower performance status (PS: >= 2) (odds ratio (OR) = 14.4; 95% confidence interval (CI): 3.6-57.7), a higher risk of unfavorable Dukes' stage (D) (OR = 4.9; 95% CI: 1.8-13.5), and a higher risk of poor grading (G3-G4) (OR = 5.0; 95% CI: 1.9-13.4). Median overall follow-up was 27 months (range: 2-212). At multivariate analysis, the only characteristics that significantly reduced the survival of the CRC patients were: HIV-positive status (hazard ratio (HR): 2.4; 95% CI: 1.1-5.2) and Dukes' stage D (HR: 3.7; 95% CI: 1.9-7.1). Conclusion: Our data show that HIV-positive CRC patients compared to HIV-negative patients have a poorer PS, an unfavorable Dukes' stage, higher grading and shorter survival.

Amelanotic melanoma (AM) is a rare subtype of melanoma with little or no clinically visible pigment; it is more difficult to diagnose than pigmented melanoma (PM), and has a worse prognosis. In the attempt to find a genetic explanation for the distinction between AM and PM, we conducted a case-case study, matching AM and PM patients, and testing them for germline mutations in high(p16INK4A, p14ARF, CDK4) and low-penetrance (MC1R) melanoma susceptibility genes. Similar CDKN2A mutations were found in both sets of melanomas. A p14ARF splice germline mutation was detected for the first time in an Italian family with AM. This rare mutation, which has been described only once previously, may be involved in predisposition to the amelanotic phenotype in combination with germline MC1R variants and coordinate somatic expression of pigmentation genes and their regulators. Melanoma Res 19:142-145 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Background & Aims Hepatocellular carcinoma (HCC) has a very poor prognosis and any effort to identify additional risk factors, besides those already established, would be important for the prevention of the disease. Data on the role of diet on HCC risk are still controversial. Methods We have evaluated the association of adherence to the Mediterranean diet with HCC risk, as well as the interaction of this dietary pattern with chronic hepatitis infection, by combining two case-control studies undertaken in Italy and Greece, including overall 518 cases of HCC and 772 controls. Adherence to the traditional Mediterranean diet was assessed through the Mediterranean diet score (MDS), which ranges between 0 (lowest adherence) and 9 (highest adherence). Odds ratios (OR) for HCC were obtained through multiple logistic regression models, controlling for potentially confounding factors, including chronic infection with hepatitis B/C viruses. Results Compared to MDS of 0-3, the ORs for HCC were 0.66 (95% confidence interval (CI), 0.41-1.04) for MDS equal to 4 and 0.51 (95% CI, 0.34-0.75) for MDS ≥5, with a significant trend (p

Scanty data are available on familial risk in oral and pharyngeal cancer. The relationship between oral and pharyngeal cancer and family history of cancer in first-degree relatives was investigated using data from a multicentric case-control study conducted in Italy and Switzerland between 1992 and 2005 on 956 cases aged less than 79 years, with histologically confirmed incident oral and pharyngeal cancer, and 2362 controls admitted to hospital for acute, nonneoplastic conditions. Logistic regression models conditioned on sex, age, study centre, and including terms for education, tobacco smoking, alcohol drinking, and number of siblings were used to estimate the odds ratios (OR) of oral and pharyngeal cancer. The multivariate ORs were similar for a family history of oral and pharyngeal cancer (2.6, 95% confidence interval, CI, 1.5-4.5) and laryngeal cancer (3.8, 95% CI, 2.0-7.2). The OR was 3.1 (95% CI, 2.0-4.8) for oral and pharyngeal cancer and laryngeal cancer combined. The OR was 7.1 (95% CI, 1.3-37.2) for subjects with 2 or more first-degree relatives with oral and pharyngeal/laryngeal cancers. Significant increases in risk were also observed for a family history of melanoma (OR = 5.8; 95% CI, 1.3-26.4) and lung cancer (OR = 1.4; 95% CI, 1.0-2.0). Compared to subjects without family history, nonsmokers, and non or moderate drinkers, the OR was 42.6 for current smokers, heavy drinkers with family history. History of oral and pharyngeal cancer and laryngeal cancer is a strong determinant of oral and pharyngeal cancer risk, independent from tobacco and alcohol. (c) 2007 Wiley-Liss, Inc.

The role of various micronutrients on the risk of renal cell cancer (RCC) was examined in a multicentric case-control study from Italy, in which information on dietary habits were collected using a validated food-frequency questionnaire. Cases were 767 patients (494 men and 273 women) with incident, histologically confirmed RCC; controls were 1,534 subjects (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, nonneoplastic conditions. After allowing for energy and other major covariates, a significant inverse association was found for vitamin E (odds ratio, OR, for the highest quintile of intake versus the lowest one 0.56, 95% confidence interval, CI 0.41-0.75), and vitamin C (OR = 0.72, 95% CI = 0.54-0.96), although the trend in risk for vitamin C was of borderline significance. No significant trend of decreasing risk was found for other micronutrients analyzed, although for most of them the risk estimates were below unity for intakes above the lowest. The ORs for the upper quintile of intake when compared with the lowest one were 0.80 (95% confidence interval, CI = 0.59-1.08) for retinol, 0.82 (95% CI = 0.61-1.10) for a-carotene, 0.90 (95% CI = 0.68-1.20) for beta-carotene, 0.94 (95% CI = 0.73-1.21) for beta-criptoxanthin, 0.85 (95% CI = 0.63-1.14) for lutein/zeaxanthin, 0.76 (95% CI = 0.57-1.01) for vitamin D, 0.75 (95% CI = 0.55-1.01) for thiamine, 0.88 (95% CI = 0.66-1.19) for riboflavin, 0.85 for vitamin B6 (95% CI = 0.64-1.13), 0.85 (95% CI = 0.64-1.12) for folate and 0.80 (95% CI = 0.60-1.07) for niacin. No meaningful associations emerged for lycopene (OR = 1.11). The present findings support a possible beneficial effect of vitamin E and C on RCC. (c) 2006 Wiley-Liss, Inc.

Mortality from oral cancer has been rising in the young in several areas of the world until the early 1990s. We analysed data from two case-control studies from Italy and Switzerland including 137 cases of oral and pharyngeal cancer below age 46 and 298 hospital controls. The multivariate odds ratios (OR) were 20.7 for heavy smokers and 4.9 for heavy drinkers. The combination of high tobacco and alcohol consumption led to an OR of over 48. Body mass index (OR=0.28, for the highest tertile), high consumption of coffee (OR=0.25), fresh vegetables (011=039), fruit (OR=0.73) and beta-carotene (OR=0.48) were inversely related to risk. Tobacco accounted for 77% of all cancer cases in this population, alcohol for 52%, low vegetable consumption for 52%, and the combination of the three factors for 85%. (C) 2003 Elsevier Ltd. All rights reserved.

Objectives. To examine the association between alcohol and the risk of prostate cancer/benign prostatic hyperplasia (BPH) in a population with a wide range of alcohol consumption, using a hospital-based, case-control study. Data from several epidemiologic studies have allowed us to exclude a strong association between alcohol drinking and prostate cancer risk. However, limited information is available for BPH. Also, it is unclear whether various types of alcoholic beverages may have a different impact on risk. Methods. We conducted this hospital-based case-control study in Italy between 1991 and 2002. A total of 2663 men younger than 75 years had incident, histologically confirmed prostate carcinoma (1294 cases) or symptomatic obstructive BPH (1369 cases) (maximal flow rate less than 15 mL/s) refractory to medical treatment. A total of 1451 patients younger than 75 years were used as controls. Odds ratios and corresponding 95% confidence intervals were estimated using unconditional multiple logistic regression models including terms for age, center, education, body mass index, physical activity, and family history of prostate cancer. Results. Alcohol consumption showed no consistent association with prostate cancer risk, but a statistically significant inverse trend in risk for BPH. Compared with abstainers, the odds ratio was 0.88 for fewer than three drinks, 0.71 for three to four drinks, 0.79 for five to six drinks, and 0.65 for seven or more drinks per day. The patterns of risk were similar with reference to different alcoholic beverages. The inverse relation between elevated alcohol consumption and BPH was apparently stronger in subjects with a lower body mass index. Conclusions. Alcohol drinking is unrelated to prostate cancer risk. The inverse relationship with BPH may be related to the hormonal correlates (ie, lower androgen levels) of heavy alcohol drinkers. UROLOGY (C) 2004 Elsevier Inc.

Objective: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. Methods: This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. Results: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for greater than or equal to25 cigarettes/day) and for duration of smoking (OR = 37.2 for greater than or equal to40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for greater than or equal to56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). Conclusions: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Objective: To investigate the relation between various micronutrients and laryngeal cancer risk. Methods: A case-control study was conducted in Italy and Switzerland between 1992 and 2000. Cases were 527 patients with incident cancer of larynx, admitted to the major teaching and general hospitals of the study areas. Controls were 1297 subjects admitted for acute, non-neoplastic diseases to the same network of hospitals. Dietary habits were assessed using a validated food-frequency questionnaire. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were computed using multiple logistic regression. Results: Significant inverse relations emerged between laryngeal cancer risk and intake of vitamin C (OR = 0.2, for the highest versus the lowest intake quintile; 95% CI: 0.2-0.4), beta-carotene (OR = 0.2; 95% CI: 0.2-0.4), alpha-carotene (OR = 0.3; 95% CI: 0.2-0.5), lutein/zeaxanthin (OR = 0.4; 95% CI: 0.3 - 0.6), vitamin E (OR = 0.4; 95% CI: 0.3 0.6), beta-criptoxanthin (OR = 0.4; 95% CI: 0.2-0.5), folic acid (OR = 0.4; 95% CI: 0.2 - 0.6), thiamin (OR = 0.4; 95% CI: 0.3 - 0.6), glutathione (OR = 0.5; 95% CI: 0.4-0.8), reduced glutathione (OR = 0.6; 95% CI: 0.4-0.8), vitamin B6 (OR = 0.6; 95% CI: 0.4 - 0.9) and potassium(OR = 0.6; 95% CI: 0.4-0.9). Direct associations were found with zinc (OR = 1.5; 95% CI: 1.0 - 2.2) and vitamin D (OR = 1.8; 95% CI: 1.2-2.6). Combining low intakes of vitamin C, carotene, vitamin E, and folate with heavy smoking and drinking led to ORs between 80 and 170. Conclusions: This study provides further support that, independently from smoking and alcohol consumption, the intake of several micronutrients, including selected antioxidants, is inversely related to laryngeal cancer risk. RI Parpinel, Maria/B-1605-2012

Background: The ability of dietary carbohydrates to affect blood glucose and insulin levels by dietary carbohydrates is best measured by the glycemic index (GI) and glycemic load (GL) which have been directly associated with risk of several chronic conditions, including cancer. Patients and methods: Three case - control studies were conducted between 1992 and 2000 in Italy. The first one included 598 hospital patients with incident, histologically confirmed oral and pharyngeal cancer and 1491 controls admitted to the same hospital networks for acute, non-neoplastic diseases; the second study included 304 subjects with squamous cell oesophageal cancer and 743 controls; the third one included 460 cases with laryngeal cancer and 1088 controls. All subjects were interviewed using a validated food frequency questionnaire. Results: The odds ratios ( OR) of upper aero-digestive tract neoplasms for the highest versus the lowest quintile of dietary GI and GL were 1.5 (95% confidence interval [CI]: 1.1 - 2.0) and 1.8 ( 95% CI: 1.1 - 2.9), respectively. The associations were in the same direction for various cancer sites. The ORs were apparently stronger in women, in those with high body mass index and reporting low alcohol consumption. Conclusions: This study supports the hypothesis that high dietary GI and GL are associated with cancers of the upper aero-digestive tract. RI Jenkins, David/A-1992-2009

Objective: This study investigates the potential role of olive oil and other added fats used for seasoning or cooking on ovarian carcinogenesis. Methods: We analyzed data from a multicentre case-control study conducted between 1992 and 1999 in Italy, including a total of 1031 incident with a first diagnosis, histologically confirmed epithelial ovarian cancer cases and 2411 hospital controls with acute, non-malignant and non-gynecological conditions. The subjects' usual diet was investigated through a validated food-frequency questionnaire, including specific questions aimed at assessing added fat intake patterns. Results: After allowance for study centre, year at interview, age, education, parity, oral contraceptive use, and total energy intake, a reduced risk of ovarian cancer was observed for high intake of olive oil (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.50-0.93 for the highest quintile of intake, compared to the lowest one) and for a group of specific seed oils (i.e. sunflower, maize, peanut, and soya) (OR = 0.59, 95% CI 0.46-0.76). No significant associations were observed for mixed seed oils, butter, and margarine. Conclusions: The present study suggests a favorable effect of olive oil and other vegetable oils on ovarian cancer in this Italian population.

COLLABORATORS (in alphabetical order of institution, study name, or location) Aichi Cancer Research Institute, Nagoya, Japan: N Hamajima, K Hirose, K Tajima; Albert Einstein College of Medicine, NY, USA: T Rohan; American Cancer Society, GA, USA: EE Calle, CW Jr Heath; Atlanta, Emory University, GA, USA: RJ Coates, JM Liff; Aviano Cancer Center, Pordenone, Italy: R Talamini; Mahidol University, Bangkok, Thailand: N Chantarakul, S Koetsawang, D Rachawat; Breast Tumor Collaborative Study, Johns Hopkins University, MD, USA: A Morabia, L Schuman, W Stewart, M Szklo; University of Queensland, Brisbane, Australia: C Bain, F Schofield, V Siskind; British Columbia Cancer Agency, BC, Canada: P Band, AJ Coldman, RP Gallagher, TG Hislop, P Yang; Cancer Research Center, University of Hawaii, Hawaii, USA: LM Kolonel, AMY Nomura; Canadian Cancer Registries Epidemiology Research Group, Canada: J Hu, KC Johnson, Y Mao; Catalán Institut of Oncology, Barcelona, Spain: S De Sanjosé; Centers for Disease Control & Prevention, GA, USA: N Lee, P Marchbanks, HW Ory, HB Peterson, HG Wilson, PA Wingo; Central Institute of Cancer Research, Berlin, Germany: K Ebeling, D Kunde, P Nishan; Centre for Genetic Epidemiology, University of Melbourne, Melbourne, Australia: JL Hopper; Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, MA, USA: G Colditz for Nurses' Health Study Research Group; Chennai Cancer Institute, Madras, India: V Gajalakshmi; Chiang Mai University, Chiang Mai, Thailand: N Martin, T Pardthaisong, S Silpisornkosol, C Theetranont; Chulalongkorn University, Bangkok, Thailand: B Boosiri, S Chutivongse, P Jimakorn, P Virutamasen, C Wongsrichanalai; Danish Cancer Society, Aalborg, Denmark: M Ewertz; Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden: HO Adami, L Bergkvist, C Magnusson, I Persson; Deutsches Krebsforschungszentrum, Heidelberg, Germany: J Chang-Claude; University of Otago, Dunedin, New Zealand: C Paul, DCG Skegg, GFS Spears; European Institute of Oncology, Milan, Italy: P Boyle, T Evstifeeva; Fred Hutchinson Cancer Research Center, WA, USA: JR Daling, WB Hutchinson, K Malone, EA Noonan, JL Stanford, DB Thomas, NS Weiss, E White; French Multicentre Breast Study, INSERM, Villejuif, France: N Andrieu, A Brêmond, F Clavel, B Gairard, J Lansac, L Piana, R Renaud; Girona Cancer Registry, Girona, Spain: A Izquierdo, P Viladiu; Hospital General de Mexico, Mexico City, Mexico: HR Cuevas, P Ontiveros, A Palet, SB Salazar; Hospital Universitario, Cali, Colombia: N Aristizabal, A Cuadros; Icelandic Cancer Society, Reykjavik, Iceland: L Tryggvadottir, H Tulinius; INSERM, Institut Gustave-Roussey, Villejuif, France: A Bachelot, MG Lê; Institute of Cancer Research, Sutton and London School of Hygiene and Tropical Medicine, UK: J Peto; International Agency for Research in Cancer, Lyon, France: S Franceschi; Israel Chaim Sheba Medical Centre, Tel-Hashomer, Israel: F Lubin, B Modan, E Ron, Y Wax; Kaiser Permanente, CA, USA: GD Friedman, RA Hiatt; Institut universitaire de medecine sociale et preventive, Lausanne, Switzerland: F Levi; Cancer Research UK Genetic Epidemiology Laboratory, Leeds, UK: T Bishop; Institute of Oncology, Ljubljana, Slovenia: K Kosmelj, M Primic-Zakelj, B Ravnihar, J Stare; Loma Linda University, CA, USA: WL Beeson, G Fraser; Cancer Research UK Department of Mathematics, Statistics & Epidemiology, London: RD Bulbrook, J Cuzick, SW Duffy, IS Fentiman, JL Hayward, DY Wang; London School of Hygiene & Tropical Medicine, London, UK: AJ McMichael, K McPherson; Long Island Breast Cancer Study, NY, USA: RL Hanson, MC Leske, MC Mahoney, PC Nasca, AO Varma, AL Weinstein; University Hospital, Lund, Sweden: TR Moller, H Olsson, J Ranstam; Maastricht University, Maastricht, The Netherlands: RA Goldbohm, PA van den Brandt; University of Philippines, Manila, Philippines: RA Apelo, J Baens, JR de la Cruz, B Javier, LB Lacaya, CA Ngelangel; Istituto ‘Mario Negri', Milan, Italy: C La Vecchia, E Negri; Istituto Nazionale Tumori, Divisione di Statistica Medica e Biometria, Milan, Italy: E Marubini; Istituto di Statistica Medica e Biometria, Milan, Italy: M Ferraroni; Montpellier Cancer Centre & INSERM, Montpellier, France: M Gerber, S Richardson, C Segala; Nairobi Centre for Research in Reproduction, Nairobi, Kenya: D Gatei, P Kenya, A Kungu, JG Mati; National Cancer Institute, MD, USA: LA Brinton, R Hoover, C Schairer; National Institute of Child Health & Human Development, MD, USA: R Spirtas; National University of Singapore, Singapore: HP Lee; The Netherlands Cancer Institute, Amsterdam, The Netherlands: MA Rookus, FE van Leeuwen for the Netherlands Oral Contraceptives and Breast Cancer Study Group; New Jersey State Department of Health, NJ, USA: JA Schoenberg; New South Wales Cancer Council, Sydney, Australia: M McCredie; Columbia University School of Public Health, NY, USA: MD Gammon; Ontario Cancer Treatment & Research Foundation, Ontario, Canada: EA Clarke; Department of Public Health & Primary Care, Oxford, UK: L Jones, A Neil, M Vessey, D Yeates; Cancer Research UK Epidemiology Unit, Oxford, UK (Secretariat): P Appleby, E Banks, V Beral, D Bull, B Crossley, A Goodill, J Green, C Hermon, T Key, N Langston, C Lewis, G Reeves; Cancer Research UK/MRC/BHF Clinical Trial Service Unit & Epidemiological Studies Unit, Oxford, UK: R Collins, R Doll, R Peto; Radiation Effects Research Foundation, Hiroshima, Japan: K Mabuchi, D Preston; Royal College of General Practitioners Oral Contraception Study, London, UK: P Hannaford, C Kay; University of Costa Rica, San Jose, Costa Rica: L Rosero-Bixby; Shanghai Cancer Institute, Shanghai, China: YT Gao, F Jin, J-M Yuan; Shanghai Institute of Planned Parenthood Research, Shanghai, China: HY Wei, T Yun, C Zhiheng; Department of Public Health, Sydney, Australia: G Berry, J Cooper Booth, T Jelihovsky, R MacLennan, R Shearman; Tianjin Cancer Institute, Tianjin, China: Q-S Wang; Department of Public Health Sciences, Toronto, Canada: CJ Baines, AB Miller, C Wall; Tromso University, Tromso, Norway: E Lund, H Stalsberg; Vanderbilt University, TN, USA: XO Shu, W Zheng; University of Athens Medical School, Athens, Greece: K Katsouyanni, A Trichopoulou, D Trichopoulos; University of Chile, Santiago, Chile: A Dabancens, L Martinez, R Molina, O Salas; University of Edinburgh, Edinburgh, UK: FE Alexander; University of Minnesota School of Public Health, MN, USA: K Anderson, AR Folsom on behalf of the Iowa Women's Health Study; University of North Carolina at Chapel Hill, School of Public Health, NC, USA: BS Hulka; University of Nottingham, Nottingham, UK: CED Chilvers; University of Southern California, LA, USA: L Bernstein, S Enger, RW Haile, A Paganini-Hill, MC Pike, RK Ross, G Ursin, MC Yu; University of Wisconsin Comprehensive Cancer Center, WI, USA: MP Longnecker, P Newcomb for the 4 State Study; Vasteras, Sweden: L Bergkvist; World Health Organisation, Geneva, Switzerland: A Kalache; World Health Organisation, UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Geneva, Switzerland: TMM Farley, S Holck, O Meirik. Analysis and writing committee: Beral V, Bull D, Doll R, Peto R, Reeves G Steering committee: Skegg D (Chairman), Colditz G, Hulka B, La Vecchia C, Magnusson C, Muller A, Peterson B, Pike M, Thomas D, Van Leeuven M.; International audience; Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but\ud it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility\ud of automatically retrieving information from the medical literature and leveraging this information in GWAS.\ud Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts,\ud and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the\ud phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can\ud subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We\ud initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and\ud subsequently applied it in a two-phase GWAS of oral cancer.\ud Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the\ud oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the\ud ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (perrare-allele\ud log additive p-value [ptrend] = 2.561023\ud ). The combined OR for having one additional rare allele was 0.83 (95% CI:\ud 0.76–0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall\ud UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper\ud aerodigestive tract (UADT), but no additional association signal was found.\ud Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical\ud literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/\ud lld/gwas/service/config).

Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons).Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.Funding Cancer Research UK.

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p trend < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p trend = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p trend = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p trend < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97). © 2011 Springer Science+Business Media B.V.

Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women’s year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons). Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women’s total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. Funding Cancer Research UK.

Background Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. Methods Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. Findings After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry. © 2011 UICC.

Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p