Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

Dixon SC, Nagle CM, Thrift AP, Pharoah PDP, Pearce CL, Zheng W, Painter JN, Chenevix-Trench G, Fasching P, Beckmann M, Lambrechts D, Vergote I, Lambrechts S, Van Nieuwenhuysen E, Rossing MA, Doherty JA, Wicklund KG, Chang-Claude J, Rudolph A, Moysich KB, Odunsi K, Goodman MT, Wilkens LR, Thompson PJ, Shvetsov YB, Doerk T, Park-Simon TW, Hillemanns P, Bogdanova N, Butzow R, Nevanlinna H, Pelttari LM, Leminen A, Modugno F, Ness RB, Edwards RP, Kelley JL, Heitz F, Karlan BY, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Cunningham JM, Winham SJ, Giles GG, Bruinsma F, Milne RL, Southey MC, Hildebrandt MAT, Wu X, Lu KH, Liang D, Levine DA, Bisogna M, Schildkraut JM, Berchuck A, Cramer DW, Terry KL, Bandera EV, Olson SH, Salvesen HB, Thomsen LC, Kopperud RK, Bjorge L, Kiemeney LA, Massuger LFAG, Pejovic T, Cook LS, Le ND, Swenerton KD, Brooks-Wilson A, Kelemen LE, Lubinski J, Huzarski T, Gronwald J, Menkiszak J, Wentzensen N, Brinton L, Yang H, Lissowska J, Hogdall CK, Lundvall L, Song H, Tyrer JP, Campbell I, Eccles D, Paul J, Glasspool R, Siddiqui N, Whittemore AS, Sieh W, Mcguire V, Rothstein JH, Narod SA, Phelan C, Risch HA, Mclaughlin JR, Anton-Culver H, Ziogas A, Menon U, Gayther SA, Ramus SJ, Gentry-Maharaj A, Wu AH, Pike MC, Tseng CC, Kupryjanczyk J, Dansonka-Mieszkowska A, Budzilowska A, Spiewankiewicz B, Webb PM (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 45

Pages Range: 884-95

Journal Issue: 3

DOI: 10.1093/ije/dyw158

Abstract

BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.

Authors with CRIS profile

Involved external institutions

Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI) Yale University United States (USA) (US) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Stanford University United States (USA) (US) Duke University United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of Texas Health Science Center at Houston (UTHealth) United States (USA) (US) University of Pittsburgh United States (USA) (US) Roswell Park Cancer Institute United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Mayo Clinic United States (USA) (US) Vanderbilt University United States (USA) (US) Cancer Council Victoria Australia (AU) Cedars-Sinai Medical Center United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Dartmouth College United States (USA) (US) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) University of Cambridge United Kingdom (GB) Kliniken Essen-Mitte Germany (DE) Fred Hutchinson Cancer Research Center Canada (CA) Memorial Sloan Kettering Cancer Center United States (USA) (US) Danish Cancer Society Research Center Denmark (DK) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) University of Kansas (KU) United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) University College London (UCL) United Kingdom (GB) National Cancer Institute (NCI) United States (USA) (US) Medical University of South Carolina (MUSC) United States (USA) (US) British Columbia Cancer Agency Canada (CA) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Glasgow Royal Infirmary (GRI) United Kingdom (GB) University of British Columbia Canada (CA) Oregon Health and Science University (OSHU) United States (USA) (US) University of Toronto Canada (CA) Radboud University Nijmegen Netherlands (NL) Texas Southern University (TSU) United States (USA) (US) Rutgers Cancer Institute of New Jersey United States (USA) (US) The University of Melbourne Australia (AU) University of Hawaii (U.H.) United States (USA) (US) University of Southern California (USC) United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) University of California Irvine United States (USA) (US) University of Michigan United States (USA) (US) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University of Copenhagen Denmark (DK) University of Southampton United Kingdom (GB) Public Health Ontario Canada (CA) Helsingin yliopisto / University of Helsinki Finland (FI) Houston Texas Medical Center United States (USA) (US)

How to cite

APA:

Dixon, S.C., Nagle, C.M., Thrift, A.P., Pharoah, P.D.P., Pearce, C.L., Zheng, W.,... Webb, P.M. (2016). Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study. International Journal of Epidemiology, 45(3), 884-95. https://dx.doi.org/10.1093/ije/dyw158

MLA:

Dixon, Suzanne C., et al. "Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study." International Journal of Epidemiology 45.3 (2016): 884-95.

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