Ko JMY, Ning L, Zhao XK, et al. - In a sample of 4,517 individuals from China, researchers investigated esophageal squamous cell carcinoma (ESCC) cancer predisposition gene(s). With 186 familial ESCC patients from high-risk China, a discovery phase was run using whole-exome sequencing. Among 3,289 Henan and 1,228 moderate-risk Hong Kong Chinese, validation was sought for 598 genes using targeted gene sequencing. Novel evidence was generated that showed a possible link of ESCC risk with DNA repair genes (POLQ and MSH2), inflammation (TTC39B) and angiogenesis (KDR). This study, for the first time ever, offers compelling evidence suggesting that BRCA2 plays a role in ESCC genetic susceptibility in Chinese patients. This implies that an underlying cause in ESCC pathogenesis is defective homologous recombination, which can be tackled by therapeutic choices based on synthetic lethality approaches such as targeting BRCA2 with PARP1 inhibitors in ESCC.