Pathogenic germline variants in BRCA1 and TP53 increase lung cancer risk in Chinese

Abstract Backgroud 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. Materials and methods We performed targeted sequencing of a CSGs panel in 1117 lung cancer patients and 16,327 controls from the general Chinese population. Results 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. Conclusion Our findings indicated that P/LP variants in BRCA1 and TP53 conferred increased risk of lung cancer in Chinese.