Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
Cancer Epidemiol Biomarkers Prev. 2018 Apr;27(4):395-404. doi: 10.1158/1055-9965.EPI-17-0315. Epub 2017 Jun 14.
In this review, we summarize current progress in the genetic epidemiology of epithelial ovarian cancer (EOC), focusing exclusively on elucidating the role of common germline genetic variation in conferring susceptibility to EOC. We provide an overview of the more than 30 EOC risk loci identified to date by genome-wide association studies (GWAS) and describe the contribution of large-scale, cross-cancer type, custom genotyping projects, such as the OncoArray and the Collaborative Oncological Gene-Environment Study, to locus discovery and replication. We discuss the histotype-specific nature of these EOC risk loci, pleiotropy, or overlapping genetic effects between EOC and other hormone-related cancer types, and the application of findings to polygenic risk prediction for EOC. The second part of the article offers a concise review of primarily laboratory-based studies that have led to the identification of several putative EOC susceptibility genes using common variants at the known EOC risk loci as starting points. More global biological insights emerging from network- and pathway-based analyses of GWAS for EOC susceptibility are also highlighted. Finally, we delve into potential future directions, including the need to identify EOC risk loci in non-European populations and the next generation of GWAS functional studies that are likely to involve genome editing to establish the cell type-specific carcinogenic effects of EOC risk variants
在这篇综述中，我们总结了上皮性卵巢癌（EOC）遗传流行病学的最新进展，专门阐明了常见种系遗传变异在赋予 EOC 易感性方面的作用。我们概述了迄今为止通过全基因组关联研究（GWAS）确定的 30 多个 EOC 风险位点，并描述了大规模、跨癌症类型的定制基因分型项目（如 OncoArray 和协同肿瘤基因-环境研究）在发现和复制位点方面的贡献。我们讨论了这些 EOC 风险位点的组织类型特异性、多效性或 EOC 与其他激素相关癌症类型之间的重叠遗传效应，以及将发现应用于 EOC 的多基因风险预测。文章的第二部分简要回顾了主要的基于实验室的研究，这些研究使用已知的 EOC 风险位点的常见变体作为起点，确定了几个假定的 EOC 易感性基因。还强调了通过 EOC 易感性的 GWAS 进行网络和途径分析所产生的更全面的生物学见解。最后，我们深入探讨了潜在的未来方向，包括需要在非欧洲人群中识别 EOC 风险位点，以及下一代可能涉及基因组编辑的 GWAS 功能研究，以确定 EOC 风险变异的细胞类型特异性致癌效应。
