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The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Background: Most studies examining post-menopausal menopausal hormone therapy (MHT) use and ovarian cancer risk have focused on White women and few have included Black women., Methods: We evaluated MHT use and ovarian cancer risk in Black (n = 800 cases, 1783 controls) and White women (n = 2710 cases, 8556 controls), using data from the Ovarian Cancer in Women of African Ancestry consortium. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MHT use with ovarian cancer risk, examining histotype, MHT type and duration of use., Results: Long-term MHT use, ≥10 years, was associated with an increased ovarian cancer risk for White women (OR = 1.38, 95%CI: 1.22-1.57) and the association was consistent for Black women (OR = 1.20, 95%CI: 0.81-1.78, p interaction  = 0.4). For White women, the associations between long-term unopposed estrogen or estrogen plus progesterone use and ovarian cancer risk were similar; the increased risk associated with long-term MHT use was confined to high-grade serous and endometroid tumors. Based on smaller numbers for Black women, the increased ovarian cancer risk associated with long-term MHT use was apparent for unopposed estrogen use and was predominately confined to other epithelial histotypes., Conclusion: The association between long-term MHT use and ovarian cancer risk was consistent for Black and White women., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Obesity disproportionately affects African American (AA) women and has been shown to increase ovarian cancer risk, with some suggestions that the association may differ by race., Methods: We evaluated body mass index (BMI) and invasive epithelial ovarian cancer (EOC) risk in a pooled study of case-control and nested case-control studies including AA and White women. We evaluated both young adult and recent BMI (within the last 5 years). Associations were estimated using multi-level and multinomial logistic regression models., Results: The sample included 1078 AA cases, 2582 AA controls, 3240 White cases and 9851 White controls. We observed a higher risk for the non-high-grade serous (NHGS) histotypes for AA women with obesity (OR BMI 30+ = 1.62, 95% CI: 1.16, 2.26) and White women with obesity (OR BMI 30+ = 1.20, 95% CI: 1.02, 2.42) compared to non-obese. Obesity was associated with higher NHGS risk in White women who never used HT (OR BMI 30+ = 1.40, 95% CI: 1.08, 1.82). Higher NHGS ovarian cancer risk was observed for AA women who ever used HT (OR BMI 30+ = 2.66, 95% CI: 1.15, 6.13), while in White women, there was an inverse association between recent BMI and risk of EOC and HGS in ever-HT users (EOC OR BMI 30+ = 0.81, 95% CI: 0.69, 0.95, HGS OR BMI 30+ = 0.73, 95% CI: 0.61, 0.88)., Conclusion: Obesity contributes to NHGS EOC risk in AA and White women, but risk across racial groups studied differs by HT use and histotype., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: No previous study has evaluated the associations of dairy products, lactose, calcium and vitamin D with the risk of ovarian cancer in African-American women, who are known to have high mortality from the disease, as well as to be at risk for calcium and vitamin D deficiency., Methods: We evaluated these associations among 490 ovarian cancer cases and 656 age- and site-matched controls of African-American descent recruited into the African American Cancer Epidemiology Study, a population-based case-control study in 11 geographical areas in the US. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: An increased ovarian cancer risk was observed for whole milk consumption and lactose intake (highest quartile vs lowest: OR=1.97, 95% CI: 1.25-3.10;P-trend: 0.008). Calcium intake was associated with a decreased risk of ovarian cancer (OR=0.51, 95 CI%: 0.30-0.86; P-trend: 0.009), but vitamin D intake was not. Longer sun exposure in summer months was found to predict a lower risk (OR=0.71, 95% CI: 0.51-0.99; P-trend: 0.049)., Conclusions: Our findings suggest that a high-calcium, low-lactose diet, and sun exposure in summer months may reduce the risk of ovarian cancer in African-American women.

Background: Existing literature examining analgesic medication use and epithelial ovarian cancer (EOC) risk has been inconsistent, with the majority of studies reporting an inverse association. Race-specific effects of this relationship have not been adequately addressed., Methods: Utilising data from the largest population-based case-control study of EOC in African Americans, the African American Cancer Epidemiology Study, the relationship between analgesic use (aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen) and risk of EOC was estimated by multivariate logistic regression. The association of frequency, duration, and indication of analgesic use on EOC risk was also assessed., Results: Aspirin use, overall, was associated with a 44% lower EOC risk (OR=0.56; 95% CI=0.35-0.92) and a 26% lower EOC risk was observed for non-aspirin NSAID use (OR=0.74; 95% CI=0.52-1.05). The inverse association was strongest for women taking aspirin to prevent cardiovascular disease and women taking non-aspirin NSAIDs for arthritis. Significantly decreased EOC risks were observed for low-dose aspirin use, daily aspirin use, aspirin use for <5 years, and occasional non-aspirin NSAID use for a duration of ⩾5 years. No association was observed for acetaminophen use., Conclusions: Collectively, these findings support previous evidence that any NSAID use is inversely associated with EOC risk.