||Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Gaitskell K, Hermon C, Moser K, Reeves G, Peto R, Brinton L, Marchbanks P, Negri E, Ness R, Peeters PH, Vessey M, Calle EE, Gapstur SM, Patel AV, Dal Maso L, Talamini R, Chetrit A, Hirsh-Yechezkel G, Lubin F, Sadetzki S, Banks E, Beral V, Bull D, Callaghan K, Crossley B, Gaitskell K, Goodill A, Green J, Hermon C, Key T, Moser K, Reeves G, Sitas F, Collins R, Doll R, Peto R, Gonzalez CA, Lee N, Marchbanks P, Ory HW, Peterson HB, Wingo PA, Martin N, Pardthaisong T, Silpisornkosol S, Theetranont C, Boosiri B, Chutivongse S, Jimakorn P, Virutamasen P, Wongsrichanalai C, Tjonneland A, Titus-Ernstoff L, Byers T, Rohan T, Mosgaard BJ, Vessey M, Yeates D, Freudenheim JL, Chang-Claude J, Kaaks R, Anderson KE, Folsom A, Robien K, Hampton J, Newcomb PA, Rossing MA, Thomas DB, Weiss NS, Riboli E, Clavel-Chapelon F, Cramer D, Hankinson SE, Tworoger SS, Franceschi S, La Vecchia C, Negri E, Adami HO, Magnusson C, Riman T, Weiderpass E, Wolk A, Schouten LJ, van den Brandt PA, Chantarakul N, Koetsawang S, Rachawat D, Palli D, Black A, Brinton LA, Freedman DM, Hartge P, Hsing AW, Lacey JV, Hoover RN, Schairer C, Urban M, Graff-Iversen S, Selmer R, Bain CJ, Green AC, Purdie DM, Siskind V, Webb PM, Moysich K, McCann SE, Hannaford P, Kay C, Binns CW, Lee AH, Zhang M, Ness RB, Nasca P, Coogan PF, Palmer JR, Rosenberg L, Kelsey J, Paffenbarger R, Whittemore A, Katsouyanni K, Trichopoulou A, Trichopoulos D, Tzonou A, Dabancens A, Martinez L, Molina R, Salas O, Goodman MT, Lurie G, Carney ME, Wilkens LR, Hartman L, Manjer J, Olsson H, Grisso JA, Morgan M, Wheeler JE, Bunker CH, Edwards RP, Modugno F, Peeters PH, Casagrande J, Pike MC, Ross RK, Wu AH, Miller AB, Kumle M, Gram IT, Lund E, McGowan L, Shu XO, Zheng W, Farley TM, Holck S, Meirik O, Risch HA
||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subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence.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 1Â·06, 95% CI 1Â·01-1Â·11, p=0Â·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)<0Â·0001). For mucinous cancers, incidence was increased in current versus never smokers (1Â·79, 95% CI 1Â·60-2Â·00, p<0Â·0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2Â·25, 95% CI 1Â·91-2Â·65 vs 1Â·49, 1Â·28-1Â·73; p(heterogeneity)=0Â·01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0Â·81, 95% CI 0Â·72-0Â·92, p=0Â·001) and clear-cell ovarian cancer risks (0Â·80, 95% CI 0Â·65-0Â·97, p=0Â·03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0Â·99, 95% CI 0Â·93-1Â·06, p=0Â·8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. INTERPRETATION: The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis. FUNDING: Cancer Research UK and MRC.