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Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study.

Publication ,  Journal Article
Harris, HR; Cushing-Haugen, KL; Webb, PM; Nagle, CM; Jordan, SJ; Australian Ovarian Cancer Study Group, ; Risch, HA; Rossing, MA; Doherty, JA ...
Published in: Int J Epidemiol
June 1, 2019

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer. METHODS: Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls). RESULTS: An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85-0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65-0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations. CONCLUSION: Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.

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Published In

Int J Epidemiol

DOI

EISSN

1464-3685

Publication Date

June 1, 2019

Volume

48

Issue

3

Start / End Page

822 / 830

Location

England

Related Subject Headings

  • Polycystic Ovary Syndrome
  • Ovarian Neoplasms
  • Neoplasms, Cystic, Mucinous, and Serous
  • Mendelian Randomization Analysis
  • Humans
  • Female
  • Epidemiology
  • Carcinoma, Endometrioid
  • Adenocarcinoma, Mucinous
  • Adenocarcinoma, Clear Cell
 

Citation

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Harris, H. R., Cushing-Haugen, K. L., Webb, P. M., Nagle, C. M., Jordan, S. J., Australian Ovarian Cancer Study Group, ., … Terry, K. L. (2019). Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study. Int J Epidemiol, 48(3), 822–830. https://doi.org/10.1093/ije/dyz113
Harris, Holly R., Kara L. Cushing-Haugen, Penelope M. Webb, Christina M. Nagle, Susan J. Jordan, Susan J. Australian Ovarian Cancer Study Group, Harvey A. Risch, et al. “Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study.Int J Epidemiol 48, no. 3 (June 1, 2019): 822–30. https://doi.org/10.1093/ije/dyz113.
Harris HR, Cushing-Haugen KL, Webb PM, Nagle CM, Jordan SJ, Australian Ovarian Cancer Study Group, et al. Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study. Int J Epidemiol. 2019 Jun 1;48(3):822–30.
Harris, Holly R., et al. “Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study.Int J Epidemiol, vol. 48, no. 3, June 2019, pp. 822–30. Pubmed, doi:10.1093/ije/dyz113.
Harris HR, Cushing-Haugen KL, Webb PM, Nagle CM, Jordan SJ, Australian Ovarian Cancer Study Group, Risch HA, Rossing MA, Doherty JA, Goodman MT, Modugno F, Ness RB, Moysich KB, Kjær SK, Høgdall E, Jensen A, Schildkraut JM, Berchuck A, Cramer DW, Bandera EV, Rodriguez L, Wentzensen N, Kotsopoulos J, Narod SA, McLaughlin JR, Anton-Culver H, Ziogas A, Pearce CL, Wu AH, Lindström S, Terry KL. Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study. Int J Epidemiol. 2019 Jun 1;48(3):822–830.
Journal cover image

Published In

Int J Epidemiol

DOI

EISSN

1464-3685

Publication Date

June 1, 2019

Volume

48

Issue

3

Start / End Page

822 / 830

Location

England

Related Subject Headings

  • Polycystic Ovary Syndrome
  • Ovarian Neoplasms
  • Neoplasms, Cystic, Mucinous, and Serous
  • Mendelian Randomization Analysis
  • Humans
  • Female
  • Epidemiology
  • Carcinoma, Endometrioid
  • Adenocarcinoma, Mucinous
  • Adenocarcinoma, Clear Cell