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

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Details zur Publikation

Autorinnen und Autoren: 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
Zeitschrift: International Journal of Epidemiology
Jahr der Veröffentlichung: 2016
Band: 45
Heftnummer: 3
Seitenbereich: 884-95
ISSN: 0300-5771


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.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


Einrichtungen weiterer Autorinnen und Autoren

Beatson West of Scotland Cancer Centre (BWSCC)
Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
Cancer Council Victoria
Cedars-Sinai Medical Center
Danish Cancer Society Research Center
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fred Hutchinson Cancer Research Center
Glasgow Royal Infirmary (GRI)
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS)
H. Lee Moffitt Cancer Center & Research Institute
Houston Texas Medical Center
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medical University of South Carolina (MUSC)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Oregon Health and Science University (OSHU)
Peter MacCallum Cancer Centre
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
Public Health Ontario
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Stanford University
Texas Southern University (TSU)
The University of Melbourne
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of British Columbia
University of California Irvine
University of Cambridge
University of Copenhagen
University of Hawaii (U.H.)
University of Kansas (KU)
University of Michigan
University of New Mexico
University of Pittsburgh
University of Southampton
University of Southern California (USC)
University of Texas Health Science Center at Houston (UTHealth)
University of Texas MD Anderson Cancer Center
University of Toronto
Vanderbilt University


Zitierweisen

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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Zuletzt aktualisiert 2019-21-07 um 07:51