Genetic variants cis-regulating Xrn2 expression contribute to the risk of spontaneous lung tumor.

ABSTRACT: Gene expression variation is an important mechanism underlying susceptibility to complex disease. In comparison with tobacco-related lung carcinogenesis, lung cancer in nonsmokers may involve important and etiologically distinct causal pathways. In this study, we conducted a genome-wide association study on spontaneous lung tumor incidence in inbred mice and identified a major susceptibility locus on mouse chromosome 2 (rs27328255, P=6.68 x 10(-7)). We then evaluated the correlations of polymorphisms with the transcription of positional candidate genes in normal lungs. Single-nucleotide polymorphism rs27328255 was consistently and strongly associated (P=7.42 x 10(-9)) in cis with transcript levels of Xrn2. We further showed that Xrn2 promotes proliferation and inhibits squamous differentia

SUBMITTER: Lu Y 

PROVIDER: S-EPMC6019621 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature