TY - JOUR
T1 - Assessment of moderate coffee consumption and risk of epithelial ovarian cancer
T2 - A Mendelian randomization study
AU - Ovarian Cancer Association Consortium
AU - Ong, Jue Sheng
AU - Hwang, Liang Dar
AU - Cuellar-Partida, Gabriel
AU - Martin, Nicholas G.
AU - Chenevix-Trench, Georgia
AU - Quinn, Michael C.J.
AU - Cornelis, Marilyn C.
AU - Gharahkhani, Puya
AU - Webb, Penelope M.
AU - MacGregor, Stuart
AU - Bryne, Enda
AU - Fasching, Peter A.
AU - Hein, Alexander
AU - Burghaus, Stefanie
AU - Beckmann, Matthias W.
AU - Lambrechts, Diether
AU - Van Nieuwenhuysen, Els
AU - Vergote, Ignace
AU - Vanderstichele, Adriaan
AU - Swerdlow, Anthony J.
AU - Jones, Michael
AU - Orr, Nicholas
AU - Schoemaker, Minouk
AU - Edwards, Digna Velez
AU - Brenton, James
AU - Benítez, Javier
AU - García, María J.
AU - Rodriguez-Antona, Cristina R.
AU - Rossing, Mary Anne
AU - Fortner, Renée T.
AU - Riboli, Elio
AU - Chang-Claude, Jenny
AU - Eilber, Ursula
AU - Wang-Gohrke, Shan
AU - Yannoukakos, Drakoulis
AU - Goodman, Marc T.
AU - Bogdanova, Natalia
AU - Dörk, Thilo
AU - Duerst, Matthias
AU - Hillemanns, Peter
AU - Runnebaum, Ingo B.
AU - Antonenkova, Natalia
AU - Butzow, Ralf
AU - Nevanlinna, Heli
AU - Pelttari, Liisa M.
AU - Edwards, Robert P.
AU - Kelley, Joseph L.
AU - Modugno, Francesmary
AU - Rothstein, Joseph H.
AU - Sieh, Weiva
N1 - Funding Information:
This work was supported by the COGS project which is funded through: a European Commission Seventh Framework Programme Grant (agreement number 223175 HEALTH F2 2009–223175); and the Genetic Associations and Mechanisms in Oncology (GAME-ON), an NCI Cancer Post-GWAS Initiative (U19-CA148112). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund, thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). Funding of the constituent studies was provided by: the California Cancer Research Program (00–01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes of Health Research (MOP-86727); Cancer Australia; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/ A10124); the Danish Cancer Society (94–222–52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; grants from the Swedish Cancer Society and European Research Council Advanced Grant ERC-2011–294576; the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; the L & S Milken Foundation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park Cancer Institute Alliance Foundation; Breast Cancer Now, the Institute of Cancer Research, NHS funding to the Royal Marsden/ ICR NIHR Biomedical Research Centre; the US National Cancer Institute (K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC67001, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA072720, P30-CA15083, P30-CA008748, P50-CA159981, P50-CA105009, P50-CA136393, R01-CA149429, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-CA095023, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R03-CA113148, R03-CA115195, U01-CA069417, U01-CA071966, UM1-CA186107, UM1-CA176726 and intramural research funds); the NIH/National Center for Research Resources/General Clinical Research Center (MO1-RR000056); the US Army Medical Research and Material Command (DAMD17–01–1–0729, DAMD17–02–1–0666, DAMD17–02–1–0669, W81XWH-07–0449, W81XWH-10–1– 02802); the US Public Health Service (PSA-042205); the National Health and Medical Research Council of Australia (199600, 400281 and 1025142); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01GB 9401); the State of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685); the German Cancer Research Center; the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; Eve Appeal; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital ‘Womens’ Health Theme’ and the Royal Marsden Hospital; and Work Safe BC 14. Investigator-specific funding: J.S. and G.C. thank the University of Queensland and QIMR Berghofer Medical Research Institute for scholarship support. G.C.T. and P.M.W. are supported by the National Health and Medical Research Council (NHMRC). S.M. acknowledges funding support from an Australian Research Council Future Fellowship. This work is also supported by the NHMRC project grant 1123248.
Funding Information:
Conflict of interest: M.T.G. is a consultant for Johnson and Johnson Ltd. U.M. has stock ownership and research funding from Abcodia Ltd, a UCL spin-out company with interest in biomarkers and ovarian cancer screening. P.F. conducts research with grants from Amgen and Novartis, and received honoraria from Amgen, Novartis, Roche, Celgene, Nanostring, Genomic Health and TEVA. J.D.B. holds stock in Inivata, the makers of DNA assays, but declares no conflict of interest regarding this work. All remaining authors declare no competing interest.
Publisher Copyright:
© The Author 2017; Published by Oxford University Press on behalf of the International Epidemiological Association all rights reserved.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Background: 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. Methods: 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 aWald-type ratio estimator. Results: 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 80mg 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. Conclusions: 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.
AB - Background: 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. Methods: 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 aWald-type ratio estimator. Results: 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 80mg 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. Conclusions: 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.
KW - Caffeine
KW - Causality
KW - Coffee
KW - Mendelian randomization
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85048363842&partnerID=8YFLogxK
U2 - 10.1093/IJE/DYX236
DO - 10.1093/IJE/DYX236
M3 - Article
C2 - 29186515
AN - SCOPUS:85048363842
SN - 0300-5771
VL - 47
SP - 450
EP - 459
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
IS - 2
ER -