Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis

Fu Z, Brooks MM, Irvin S, Jordan S, Aben KKH, Anton-Culver H, Bandera E, Beckmann M, Berchuck A, Brooks-Wilson A, Chang-Claude J, Cook LS, Cramer DW, Cushing-Haugen KL, Doherty JA, Ekici AB, Fasching P, Fortner RT, Gayther SA, Gentry-Maharaj A, Giles GG, Goode EL, Goodman MT, Harris HR, Hein A, Kaaks R, Kiemeney LA, Koebel M, Kotsopoulos J, Le ND, Lee AW, Matsuo K, Mcguire V, Mclaughlin JR, Menon U, Milne RL, Moysich KB, Pearce CL, Pike MC, Qin B, Ramus SJ, Riggan MJ, Rothstein JH, Schildkraut JM, Sieh W, Sutphen R, Terry KL, Thompson PJ, Titus L, Van Altena AM, White E, Whittemore AS, Wu AH, Zheng W, Ziogas A, Taylor SE, Tang L, Songer T, Wentzensen N, Webb PM, Risch HA, Modugno F (2023)

Publication Type: Journal article

Publication year: 2023

Journal

DOI: 10.1093/jnci/djad011

Abstract

Background The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. Methods LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. Results LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. Conclusions LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.

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Involved external institutions

University of Pittsburgh United States (USA) (US) Radboud University Nijmegen Netherlands (NL) University of California Irvine United States (USA) (US) University of Queensland Australia (AU) National Cancer Institute (NCI) United States (USA) (US) Rutgers Cancer Institute of New Jersey United States (USA) (US) University College London (UCL) United Kingdom (GB) Cedars-Sinai Medical Center United States (USA) (US) Mayo Clinic United States (USA) (US) University of Toronto Canada (CA) Vancouver General Hospital Canada (CA) University of Calgary Canada (CA) Memorial Sloan Kettering Cancer Center United States (USA) (US) Roswell Park Cancer Institute United States (USA) (US) University of South Florida (USF) United States (USA) (US) California State University (CSUF) United States (USA) (US) University of New South Wales (UNSW) Australia (AU) Stanford University United States (USA) (US) Cancer Council Victoria Australia (AU) Aichi Cancer Center Research Institute Japan (JP) Vanderbilt University Medical Center United States (USA) (US) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) Netherlands (NL) Emory University United States (USA) (US) Icahn School of Medicine at Mount Sinai United States (USA) (US) University of Maine System (UMS) United States (USA) (US) University of Washington United States (USA) (US)

How to cite

APA:

Fu, Z., Brooks, M.M., Irvin, S., Jordan, S., Aben, K.K.H., Anton-Culver, H.,... Modugno, F. (2023). Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis. Journal of the National Cancer Institute. https://dx.doi.org/10.1093/jnci/djad011

MLA:

Fu, Zhuxuan, et al. "Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis." Journal of the National Cancer Institute (2023).

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