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

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

SUBMITTER: Ji X 

PROVIDER: S-EPMC7214407 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature