Department of Molecular Pathology, Henan Key Laboratory of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China.
Nanjing Shenyou Institute of Genome Research, Nanjing, Jiangsu, China.
Cancer Med. 2023 Dec;12(23):21219-21228. doi: 10.1002/cam4.6692. Epub 2023 Nov 6.
Multiple studies have identified pathogenic germline variants in cancer susceptibility genes (CSGs) in Chinese lung cancer patients; however, accurate assessment of these variants' contributions to cancer predisposition is always hampered by the absence of data on the prevalence of these variants in the general population. It is necessary to conduct a large-scale case-control study to identify CSGs that significantly increase the risk of lung cancer.
We performed targeted sequencing of a CSGs panel in 1117 lung cancer patients and 16,327 controls from the general Chinese population.
In comparison to controls, lung cancer patients had a considerably higher prevalence of pathogenic and likely pathogenic (P/LP) variations. Among lung cancer patients, 72% of P/LP variants carriers did not have a family cancer history, who would be ignored if germline testing was only provided for patients meeting family history-based criteria. Furthermore, compared to individuals with late-onset lung cancer, patients with early-onset lung cancer had a considerably higher prevalence of P/LP variations. With odds ratios (ORs) ranging from 4-fold (BRCA1: OR, 4.193; 95%CI, 1.382-10.768) to 29-fold (TP53: OR, 29.281; 95%CI, 1.523-1705.506), P/LP variants in the BRCA1 and TP53 genes were discovered to be strongly related to increased lung cancer risk. Additionally, with ORs ranging from 7.322-fold to infinity, we discovered 23 variations previously categorized as non-P/LP variants were highly enriched in lung cancer patients.
Our findings indicated that P/LP variants in BRCA1 and TP53 conferred increased risk of lung cancer in Chinese.
多项研究已经在中国肺癌患者的癌症易感性基因（CSG）中发现了致病性种系变异；然而，由于缺乏这些变异在普通人群中的流行数据，因此总是难以准确评估这些变异对癌症易感性的贡献。有必要开展一项大规模的病例对照研究，以确定显著增加肺癌风险的 CSG。
我们对来自普通中国人群的 1117 名肺癌患者和 16327 名对照进行了 CSG 面板的靶向测序。
与对照相比，肺癌患者致病性和可能致病性（P/LP）变异的发生率明显更高。在肺癌患者中，72%的 P/LP 变异携带者没有家族癌症史，如果仅为符合家族史标准的患者提供种系检测，这些人将被忽略。此外，与晚发性肺癌患者相比，早发性肺癌患者 P/LP 变异的发生率明显更高。BRCA1 基因中的 P/LP 变异（OR，4.193；95%CI，1.382-10.768）和 TP53 基因中的 P/LP 变异（OR，29.281；95%CI，1.523-1705.506）与肺癌风险显著增加相关，其比值比（OR）范围从 4 倍到 29 倍不等。此外，我们发现 23 个以前归类为非 P/LP 变异的变异在肺癌患者中高度富集，其 OR 范围从 7.322 倍到无穷大。
我们的研究结果表明，BRCA1 和 TP53 中的 P/LP 变异在中国人群中增加了肺癌的风险。
