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Int J Epidemiol. 2018 Apr 1;47(2):450-459. doi: 10.1093/ije/dyx236.

Assessment of moderate coffee consumption and risk of epithelial ovarian cancer: a Mendelian randomization study.

Collaborators (134)

Ong JS, Hwang LD, Cuellar-Partida G, Bryne E, Fasching PA, Hein A, Burghaus S, Beckmann MW, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Vanderstichele A, Swerdlow AJ, Jones M, Orr N, Schoemaker M, Edwards DV, Brenton J, Benítez J, García MJ, Rodriguez-Antona C, Rossing MA, Fortner RT, Riboli E, Chang-Claude J, Eilber U, Wang-Gohrke S, Yannoukakos D, Goodman MT, Bogdanova N, Dörk T, Duerst M, Hillemanns P, Runnebaum IB, Antonenkova N, Butzow R, Nevanlinna H, Pelttari LM, Edwards RP, Kelley JL, Modugno F, Moysich KB, Ness RB, Cannioto R, Heitz F, Karlan B, Olsson H, Kjaer SK, Jensen A, Giles GG, Bruinsma F, Hildebrandt MAT, Liang D, Wu X, Le Marchand L, Setiawan VW, Permuth JB, Bisogna M, Dao F, Levine DA, Cramer DW, Terry KL, Tworoger SS, Stampfer M, Willet W, Missmer S, Bjorge L, Kopperud RK, Bischof K, Thomsen LCV, Kiemeney LA, Massuger LF, Pejovic T, Brooks-Wilson A, Olson SH, McGuire V, Rothstein JH, Sieh W, Whittemore AS, Cook LS, Le ND, Gilks CB, Gronwald J, Jakubowska A, Lubiński J, Kluz T, Wentzensen N, Brinton L, Trabert B, Lissowska J, Høgdall E, Høgdall CK, Sandler DP, Wolk A, Tyrer JP, Song H, Eccles D, Campbell I, Glasspool R, McNeish I, Paul J, Siddiqui N, Sutphen R, McLaughlin JR, Phelan C, Anton-Culver H, Ziogas A, May T, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Wu AH, Huntsman D, deFazio A, Dansonka-Mieszkowska A, Kupryjanczyk J, Moes-Sosnowska J, Szafron LM, Cunningham JM, Winham SJ, Risch HA, Goode EL, Schildkraut JM, Pearce CL, Berchuck A, Pharoah PDP, Martin NG, Chenevix-Trench G, Quinn MCJ, Cornelis MC, Gharahkhani P, Webb PM, MacGregor S.

Author information

Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
School of Medicine, University of Queensland, St Lucia, QLD, Australia.
Northwestern University Feinberg School of Medicine, Preventive Medicine, Chicago, IL, USA.
Population Health Department, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.



Coffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal.


We used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data on 44 062 individuals of European ancestry from the Ovarian Cancer Association Consortium (OCAC), and combined instrumental variable estimates using a Wald-type ratio estimator.


For all EOC cases, the causal odds ratio (COR) for genetically predicted consumption of one additional cup of coffee per day was 0.92 [95% confidence interval (CI): 0.79, 1.06]. The COR was 0.90 (95% CI: 0.73, 1.10) for high-grade serous EOC. The COR for genetically predicted consumption of an additional 80 mg caffeine was 1.01 (95% CI: 0.92, 1.11) for all EOC cases and 0.90 (95% CI: 0.73, 1.10) for high-grade serous cases.


We found no evidence indicative of a strong association between EOC risk and genetically predicted coffee or caffeine levels. However, our estimates were not statistically inconsistent with earlier observational studies and we were unable to rule out small protective associations.

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