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

Publication ,  Journal Article
Dixon, SC; Nagle, CM; Thrift, AP; Pharoah, PD; Pearce, CL; Zheng, W; Painter, JN; AOCS Group & Australian Cancer Study (Ovarian Cancer), ; Wu, X ...
Published in: Int J Epidemiol
June 2016

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.

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Published In

Int J Epidemiol

DOI

EISSN

1464-3685

Publication Date

June 2016

Volume

45

Issue

3

Start / End Page

884 / 895

Location

England

Related Subject Headings

  • Young Adult
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Obesity
  • Multivariate Analysis
  • Middle Aged
  • Meta-Analysis as Topic
  • Mendelian Randomization Analysis
  • Logistic Models
 

Citation

APA
Chicago
ICMJE
MLA
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Dixon, S. C., Nagle, C. M., Thrift, A. P., Pharoah, P. D., Pearce, C. L., Zheng, W., … Ovarian Cancer Association Consortium, . (2016). Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study. Int J Epidemiol, 45(3), 884–895. https://doi.org/10.1093/ije/dyw158
Dixon, Suzanne C., Christina M. Nagle, Aaron P. Thrift, Paul Dp Pharoah, Celeste Leigh Pearce, Wei Zheng, Jodie N. Painter, et al. “Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study.Int J Epidemiol 45, no. 3 (June 2016): 884–95. https://doi.org/10.1093/ije/dyw158.
Dixon SC, Nagle CM, Thrift AP, Pharoah PD, Pearce CL, Zheng W, et al. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study. Int J Epidemiol. 2016 Jun;45(3):884–95.
Dixon, Suzanne C., et al. “Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study.Int J Epidemiol, vol. 45, no. 3, June 2016, pp. 884–95. Pubmed, doi:10.1093/ije/dyw158.
Dixon SC, Nagle CM, Thrift AP, Pharoah PD, Pearce CL, Zheng W, Painter JN, AOCS Group & Australian Cancer Study (Ovarian Cancer), Chenevix-Trench G, Fasching PA, Beckmann MW, 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, Dörk T, Park-Simon T-W, Hillemanns P, Bogdanova N, Butzow R, Nevanlinna H, Pelttari LM, Leminen A, Modugno F, Ness RB, Edwards RP, Kelley JL, Heitz F, Karlan BY, Kjær SK, Høgdall 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, Lubiński J, Huzarski T, Gronwald J, Menkiszak J, Wentzensen N, Brinton L, Yang H, Lissowska J, Høgdall 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 C-C, Kupryjanczyk J, Dansonka-Mieszkowska A, Budzilowska A, Spiewankiewicz B, Webb PM, Ovarian Cancer Association Consortium. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study. Int J Epidemiol. 2016 Jun;45(3):884–895.
Journal cover image

Published In

Int J Epidemiol

DOI

EISSN

1464-3685

Publication Date

June 2016

Volume

45

Issue

3

Start / End Page

884 / 895

Location

England

Related Subject Headings

  • Young Adult
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Obesity
  • Multivariate Analysis
  • Middle Aged
  • Meta-Analysis as Topic
  • Mendelian Randomization Analysis
  • Logistic Models