Expanding our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies

Alice W. Lee, PhD; Stacey Rosenzweig, MPH; Ashley Wiensch, MPH, the Australian Ovarian Cancer Study Group; Susan J. Ramus, PhD; Usha Menon, MD; Aleksandra Gentry-Maharaj, PhD; Argyrios Ziogas, PhD; Hoda Anton-Culver, PhD; Alice S. Whittemore, PhD; Weiva Sieh, PhD, MD; Joseph H. Rothstein, MS; Valerie McGuire, PhD; Nicolas Wentzensen, PhD, MD; Elisa V. Bandera, PhD, MD; Bo Qin, PhD; Kathryn L. Terry, ScD; Daniel W. Cramer, ScD, MD; Linda Titus, PhD; Joellen M. Schildkraut, PhD; Andrew Berchuck, MD; Ellen L. Goode, PhD; Susanne K. Kjaer, DMSc, MD; Allan Jensen, PhD; Susan J. Jordan, PhD; Roberta B. Ness, MD, MPH; Francesmary Modugno, PhD; Kirsten Moysich, PhD; Pamela J. Thompson, MPH; Marc T. Goodman, PhD; Michael E. Carney, MD; Jenny Chang-Claude, PhD; Mary Anne Rossing, PhD, DVM; Holly R. Harris, ScD; Jennifer Anne Doherty, PhD; Harvey A. Risch, PhD, MD; Lilah Khoja, MPH; Aliya Alimujiang, MPH; Minh Tung Phung, MPH; Katharine Brieger, PhD; Bhramar Mukherjee, PhD; Paul D.P. Pharoah, PhD, MD; Anna H. Wu, PhD; Malcolm C. Pike, PhD; Penelope M. Webb, PhD; Celeste Leigh Pearce, PhD

Disclosures

J Natl Cancer Inst. 2021;113(3):301-308. 

In This Article

Abstract and Introduction

Abstract

Background: Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated.

Methods: A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses.

Results: Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided P trend < .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer.

Conclusions: Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

Introduction

Parity is associated with a decreased risk of ovarian carcinoma (cancer) in a dose-dependent manner.[1–3] Compared to nulliparous women, women with 1 birth have an approximate 24% (95% confidence interval [CI] = 12% to 34%) decrease in risk, and women with 2 or more births have an approximate 42% (95% CI = 35% to 49%) risk reduction.[1]

However, the association between incomplete pregnancies (induced and spontaneous abortions) and ovarian cancer risk is unclear. Some studies[4–7] and 1 pooled analysis of 6 population-based case-control studies[8] have reported a decreased risk. However, a number of studies have reported a null association,[9–15] and 1 reported an increased risk,[16] but there was no adjustment for any potential confounders in this study. Whether the association might differ by histotype has not been adequately studied because of limited numbers. Because different histotypes likely represent distinct diseases with different risk factors,[17] understanding the association by histotype may provide insight into their etiologies.

Given the equivocal literature, we evaluated the relationship between incomplete pregnancies and ovarian cancer risk using data from 15 case-control studies with data on incomplete pregnancies from the Ovarian Cancer Association Consortium (OCAC); some data from 2 of these studies have been published previously.[10,12] We have included 10 470 women with ovarian cancer and 16 942 controls. This is the largest analysis of this relationship, allowing us to consider histotype-specific associations with sufficient sample sizes.

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