BackgroundGenes in the homologous recombination pathway have shown varying results in the literature regarding ovarian cancer (OC) association. Recent case-control studies have used allele counts alone to quantify genetic associations with cancer.MethodsA retrospective case-control study was performed on 6,182 women with OC referred for hereditary cancer multi-gene panel testing (cases) and 4,690 mothers from trios who were referred for whole-exome sequencing (controls). We present age-adjusted odds ratios (ORAdj) to determine association of OC with pathogenic variants (PVs) in homologous recombination genes.ResultsSignificant associations with OC were observed in BRCA1, BRCA2, RAD51C and RAD51D. Other homologous recombination genes, BARD1, NBN, and PALB2, were not significantly associated with OC. ATM and CHEK2 were only significantly associated with OC by crude odds ratio (ORCrude) or by ORAdj, respectively. However, there was no significant difference between ORCrude and ORAdj for these two genes. The significant association of PVs in BRIP1 by ORCrude (2.05, CI = 1.11 to 3.94, P = 0.03) was not observed by ORAdj (0.87, CI = 0.41 to 1.93, P = 0.73). Interestingly, the confidence intervals of the two effect sizes were significantly different (P = 0.04).ConclusionThe lack of association of PVs in BRIP1 with OC by ORAdj is inconsistent with some previous literature and current management recommendations, highlighted by the significantly older age of OC onset for BRIP1 PV carriers compared to non-carriers. By reporting ORAdj, this study presents associations that reflect more informed genetic contributions to OC when compared to traditional count-based methods.

中文翻译：

---

使用临床外显子组作为对照的同源重组基因与卵巢癌的年龄调整关联

背景同源重组途径中的基因在有关卵巢癌 (OC) 关联的文献中显示出不同的结果。最近的病例对照研究仅使用等位基因计数来量化与癌症的遗传关联。方法对 6,182 名患有 OC 的女性进行了回顾性病例对照研究，这些女性被转诊进行遗传性癌症多基因面板测试（病例）和 4,690 名来自三重奏的母亲被转诊用于全外显子组测序（对照）。我们提出年龄调整优势比 (ORAdj) 以确定 OC 与同源重组基因中的致病变异 (PVs) 的关联。结果在 BRCA1、BRCA2、RAD51C 和 RAD51D 中观察到与 OC 的显着关联。其他同源重组基因 BARD1、NBN 和 PALB2 与 OC 没有显着相关性。ATM 和 CHEK2 仅通过粗比值比 (ORCrude) 或 ORAdj 分别与 OC 显着相关。然而，这两个基因的 ORCrude 和 ORAdj 之间没有显着差异。ORAdj (0.87, CI = 0.41 至 1.93, P = 0.73) 未观察到 ORCrude (2.05, CI = 1.11 至 3.94, P = 0.03) 与 BRIP1 中 PV 的显着关联。有趣的是，两种效应量的置信区间存在显着差异（P = 0.04）。结论 ORAdj 将 BRIP1 中的 PV 与 OC 缺乏关联与以前的一些文献和当前的管理建议不一致，尤其是 OC 的年龄显着增加与非载体相比，BRIP1 PV 载体的发病率。通过报告 ORAdj，