Protein-altering germline mutations implicate novel genes related to lung cancer development.

摘要: Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals European ancestry and investigated gene expression levels in 7,773 samples. find a large-effect association with an ATM L2307F (rs56009889) mutation adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) replication OR = 2.93, P = 2.22 × 10-3) that is more pronounced females OR = 6.81 3.19 replication). observe excess loss heterozygosity tumors among allele carriers. frequent (4%) Ashkenazi Jewish populations. also OR = 2.61, P = 7.98 × 10-22) datasets OR = 1.55, P = 0.06) loss-of-function mutation, Q4X (rs150665432) uncharacterized gene, KIAA0930. Our findings implicate genetic susceptibility suggest KIAA0930 as novel candidate