Patterns of Associations with Epidemiologic Factors by High-Grade Serous Ovarian Cancer Gene Expression Subtypes.

IF 3.7 3区医学 Q2 ONCOLOGY

Cancer Epidemiology Biomarkers & Prevention Pub Date : 2025-05-02 DOI:10.1158/1055-9965.EPI-24-1143

Lindsay J Collin, Kara L Cushing-Haugen, Kathryn L Terry, Ellen L Goode, Anna H Wu, Holly R Harris, Naoko Sasamoto, Daniel W Cramer, Francesmary Modugno, Esther Elishaev, Zhuxuan Fu, Kirsten B Moysich, Peter A Fasching, Celeste Leigh Pearce, Usha Menon, Aleksandra Gentry-Maharaj, Simon A Gayther, Nicolas Wentzensen, Marc T Goodman, Joshy George, Aline Talhouk, Michael S Anglesio, Susan J Ramus, David D L Bowtell, Shelley S Tworoger, Joellen M Schildkraut, Penelope M Webb, Jennifer A Doherty

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Abstract

Background: Ovarian high-grade serous carcinomas (HGSC) comprise four distinct molecular subtypes based on mRNA expression patterns, with differential survival. Understanding risk factor associations is important to elucidate the etiology of HGSC. We investigated associations between different epidemiologic risk factors and HGSC molecular subtypes.

Methods: We pooled data from 11 case-control studies with epidemiologic and tumor gene expression data from custom NanoString CodeSets developed through a collaboration within the Ovarian Tumor Tissue Analysis consortium. The PrOTYPE-validated NanoString-based 55-gene classifier was used to assign HGSC gene expression subtypes. We examined associations between epidemiologic factors and HGSC subtypes in 2,070 cases and 16,633 controls using multivariable-adjusted polytomous regression models.

Results: Among the 2,070 HGSC cases, 556 (27%) were classified as C1.MES, 340 (16%) as C5.PRO, 538 (26%) as C2.IMM, and 636 (31%) as C4.DIF. The key factors, including oral contraceptive use, parity, breastfeeding, and family history of ovarian cancer, were similarly associated with all subtypes. Heterogeneity was observed for several factors. Former smoking [OR = 1.25; 95% confidence interval (CI) = 1.03, 1.51] and genital powder use (OR = 1.42; 95% CI = 1.08, 1.86) were uniquely associated with C2.IMM. History of endometriosis was associated with C5.PRO (OR = 1.46; 95% CI = 0.98, 2.16) and C4.DIF (OR = 1.27; 95% CI = 0.94, 1.71) only. Family history of breast cancer (OR = 1.44; 95% CI = 1.16, 1.78) and current smoking (OR = 1.40; 95% CI = 1.11, 1.76) were associated with C4.DIF only.

Conclusions: This study observed heterogeneous associations of epidemiologic and modifiable factors with HGSC molecular subtypes.

Impact: The different patterns of associations may provide key information about the etiology of the four subtypes.

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高级别浆液性卵巢癌基因表达亚型与流行病学因素的关联模式

背景：基于mRNA表达模式，卵巢高级别浆液性癌（HGSC）包括四种不同的分子亚型，生存率不同。了解危险因素的关联对于阐明HGSC的病因是很重要的。我们调查了不同流行病学危险因素与HGSC分子亚型之间的关系。方法：我们汇集了11项病例对照研究的数据，这些数据来自于由卵巢肿瘤组织分析协会（Ovarian tumor Tissue Analysis Consortium）合作开发的定制NanoString CodeSets的流行病学和肿瘤基因表达数据。使用PrOTYPE验证的NanoString-based 55基因分类器对HGSC基因表达亚型进行分类。我们使用多变量调整的多元回归模型，研究了2070例病例和16633例对照的流行病学因素与HGSC亚型之间的关系。结果：2070例HGSC中，556例（27%）为C1级。MES, 340（16%）为C5。PRO, 538（26%）为C2。C4.DIF 636例（31%）。关键因素，包括口服避孕药的使用、胎次、母乳喂养和卵巢癌家族史，与所有亚型相似。有几个因素存在异质性。既往吸烟（OR=1.25, 95%CI: 1.03, 1.51）和生殖器爽身粉使用（OR=1.42, 95%CI: 1.08, 1.86）与C2.IMM有独特的相关性。子宫内膜异位症病史与C5相关。PRO （OR=1.46, 95%CI: 0.98, 2.16）和C4。仅DIF （OR=1.27, 95%CI: 0.94, 1.71）。乳腺癌家族史（OR=1.44, 95%CI: 1.16, 1.78）和吸烟史（OR=1.40, 95%CI: 1.11, 1.76）与C4相关。DIF。结论：本研究观察到流行病学和可改变因素与HGSC分子亚型的异质性关联。影响：不同的关联模式可能为四种亚型的病因学提供关键信息。

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来源期刊

Cancer Epidemiology Biomarkers & Prevention 医学-公共卫生、环境卫生与职业卫生

CiteScore

6.50

自引率

2.60%

发文量

538

审稿时长

1.6 months

期刊介绍： Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.