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
Book Volume: 45
Pages Range: 884-95
Journal Issue: 3
DOI: 10.1093/ije/dyw158
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.
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://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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