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Ovarian cancer incidence has declined in recent decades, due in part to oral contraceptive (OC) use and tubal ligation. However, intrauterine device (IUD) use has increasingly replaced OC use. As ovarian cancer is an inflammation-related disease, we examined the association of OC use, IUD use, and tubal ligation with plasma levels of C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor α receptor 2 in the Nurses' Health Study (NHS) and NHSII. After adjusting for reproductive, hormonal, and lifestyle factors and mutual adjustment for other methods of contraception, there were no differences in inflammatory markers between ever and never use of each method. However, CRP levels decreased from an average of 30.4% (95% CI, -53.6 to 4.4) with every 5 years since initial IUD use (P-trend = .03), while CRP increased an average of 9.9% (95% CI, 5.7, 14.3) with every 5 years of use of OC (P-trend < .0001) as well as differences by body mass index and menopausal status. Our results suggest IUD use and tubal ligation are not associated with higher circulating inflammatory markers long term, although long duration of OC use may increase generalized inflammation, which may in part explain why its protective effect wanes over time. This article is part of a Special Collection on Gynecological Cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS)., Methods: We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan., Results: Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3'-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76×10 -9 ). The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95%CI:1.37-1.54) per standard deviation in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62)., Conclusions: This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC.

Introduction: Over four million women in the US alone have been diagnosed with endometriosis. For those living with this disease, surgery and hormonal treatment reduce associated pelvic pain in some, while others continue to experience life impacting pain. Therefore, identification of accessible and cost-effective methods of pain reduction to compliment current treatment is urgently needed. Our objective was to quantify the prevalence of complementary and alternative methods used to manage acyclic pelvic pain and their reported benefit among women of different age groups living with endometriosis., Methods: We used baseline questionnaire data from laparoscopically-confirmed endometriosis cases who completed a WERF EPHect compliant questionnaire in the longitudinal cohort of The Women's Health Study: From Adolescence to Adulthood (A2A). Participants with acyclic pelvic pain were asked to indicate specific methods or activities that either helped or worsened their pelvic/lower abdominal pain. Differences among age groups [adolescent (<18 years), young adult (18-25 years), and adult (>25 years)] were assessed using Fisher's exact test., Results: Of the 357 participants included in analysis, sleep for coping was reported more frequently among adolescents ( n  = 59, 57.3%) compared to young adults ( n  = 40, 44.0%) and adults ( n  = 19, 31.1%; p  = 0.004). Adolescents also reported more frequent use of music ( n  = 29, 21.2%) than young adults ( n  = 10, 7.0%) and adults ( n  = 7, 9.1%; p  = 0.001). Exercise worsened pain most commonly among adolescents ( n  = 82, 59.9%), followed by younger adults ( n  = 67, 46.9%), and adults ( n  = 27, 35.1%; p  = 0.002)., Discussion: Our analysis of participants in the A2A cohort showed that the prevalence of complementary and alternative methods used for coping with endometriosis-associated acyclic pelvic pain varied by age group. Future studies should aim to provide information that will further inform decisions in making care plans for managing endometriosis-associated pain that is effective, accessible, and tailored to the preferences of the patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Mongiovi, Wallace, Goodwin, Vitonis, Karevicius, Shafrir, Sasamoto, DiVasta, Sieberg, Terry and Missmer.)