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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subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence.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)

SummaryBackgroundHalf the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall.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.MethodsIndividual 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.FindingsDuring 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

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 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.

The prevalence of obesity at all ages is increasing epidemically worldwide. Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce. In 1991 to 1992, a prospective cohort study was assembled in Norway and Sweden. We included in the analysis presented here 99,717 premenopausal women. During the follow-up period, which ended in December 1999, 733 of these women developed a primary invasive breast cancer. Overweight and obesity [body mass index (BMI) > 25 kg/m2] at enrolment was associated with a decreased risk of premenopausal breast cancer (P for linear trend = 0.007). Apparent associations between perceived body shape at age 7 and BMI at age 18, with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk, lost their statistical significance after adjustment for BMI at cohort enrolment. Body size at age 7 was correlated with BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48). Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk. Height was related to risk, with a statistically significantly 30% reduced risk only in women shorter than 160 cm as compared with taller ones. The decreased risk of premenopausal breast cancer was observed in overweight and obese women without, but not in those with, a family history of breast cancer.

Background The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project. Methods We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978–2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use. Results Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20–1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15–1.41) and other cause mortality (aHR 1.37, 95% CI 1.24–1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00–1.26). These mortality risks increased with duration of snus use, but not with weekly amount. Conclusions Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality.

The use of snus (also referred to as Scandinavian or Swedish moist smokeless tobacco), which is common in Sweden and increasing elsewhere, is receiving increasing attention since considered a tobacco smoke "potential reduction exposure product". Snus delivers a high dose of nicotine with possible hemodynamic effects, but its impact on cardiovascular morbidity and mortality is uncertain. The aim of this study was to investigate whether snus use is associated with risk of and survival after acute myocardial infarction (AMI). Data from eight prospective cohort studies set in Sweden was pooled and reanalysed. The relative risk of first time AMI and 28-day case-fatality was calculated for 130,361 men who never smoked. During 2,262,333 person-years of follow-up, 3,390 incident events of AMI were identified. Current snus use was not associated with risk of AMI (pooled multivariable hazard ratio 1.04, 95% confidence interval 0.93 to 1.17). The short-term case fatality rate appeared increased in snus users (odds ratio 1.28, 95% confidence interval 0.99 to 1.68). This study does not support any association between use of snus and development of AMI. Hence, toxic components other than nicotine appear implicated in the pathophysiology of smoking related ischemic heart disease. Case fatality after AMI is seemingly increased among snus users, but this relationship may be due to confounding by socioeconomic or life style factors.

Background: Snus is a smokeless tobacco product, widely used among Swedish men and increasingly so elsewhere. There is debate as to whether snus is an acceptable "harm-reduction" tobacco product. Since snus use delivers a dose of nicotine equivalent to cigarettes, and has been implicated in cardiac arrhythmia because of associations with sudden cardiovascular death, a relation with atrial fibrillation is plausible and important to investigate. Methods: To assess the relation between use of snus and risk of atrial fibrillation, we carried out a pooled analysis of 7 prospective Swedish cohort studies. In total, 274,882 men, recruited between 1978 and 2004, were followed via the National Patient Register for atrial fibrillation. Primary analyses were restricted to 127,907 never-smokers. Relative risks were estimated using Cox proportional hazard regression. Results: The prevalence of snus use was 25% among never-smokers. During follow-up, 3,069 cases of atrial fibrillation were identified. The pooled relative risk of atrial fibrillation was 1.07 (95% confidence interval = 0.97-1.19) in current snus users, compared with nonusers. Conclusion: Findings from this large national pooling project indicate that snus use is unlikely to confer any important increase in risk of atrial fibrillation

Background: Cigarette smoking is associated with a lower risk of Parkinson's disease. It is unclear what constituent of tobacco smoke may lower the risk. Use of Swedish moist smokeless tobacco (snus) can serve as a model to disentangle what constituent of tobacco smoke may lower the risk. The aim of this study was to determine whether snus use was associated with a lower risk of Parkinson's disease. Methods: Individual participant data were collected from seven prospective cohort studies, including 348 601 men. We used survival analysis with multivariable Cox regression to estimate study-specific relative risk of Parkinson's disease due to snus use, and random-effects models to pool estimates in a meta-analysis. The primary analyses were restricted to never-smokers to eliminate the potential confounding effect of tobacco smoking. Results: During a mean follow-up time of 16.1 years, 1199 incident Parkinson's disease cases were identified. Among men who never smoked, ever-snus users had about 60% lower Parkinson's disease risk compared with never-snus users [pooled hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.61]. The inverse association between snus use and Parkinson's disease risk was more pronounced in current (pooled HR 0.38, 95% CI 0.23-0.63), moderate-heavy amount (pooled HR 0.41, 95% CI 0.19-0.90) and long-term snus users (pooled HR 0.44, 95% CI 0.24-0.83). Conclusions: Non-smoking men who used snus had a substantially lower risk of Parkinson's disease. Results also indicated an inverse dose-response relationship between snus use and Parkinson's disease risk. Our findings suggest that nicotine or other components of tobacco leaves may influence the development of Parkinson's disease.