The eQTL-missense polymorphisms of APOBEC3H are associated with lung cancer risk in a Han Chinese population

APOBEC (Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) enzymes may involve in mutagenic processes in multiple cancer types, including lung cancer. APOBEC family of cytidine deaminases induces base substitutions with a stringent TCW motif, which is widespread in multiple human cancers. We hypothesized that common missense variants in coding regions of APOBEC genes might damage the structure of proteins and modify lung cancer risk. To test this hypothesis, we systematically screened predicted deleterious polymorphisms in the exon regions of 10 APOBEC core genes (APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D, APOBEC3F, APOBEC3G, APOBEC3H, and APOBEC4) and evaluated them with a case-control study including 1200 cases and 1253 controls. We found that the T allele of rs139293 in exon 2 of APOBEC3H was significantly associated with decreased risk of lung cancer (odds ratio = 0.76, 95% confidence interval: 0.63-0.91). Similar inverse association of this variant was observed in subgroups. Further study showed that the T allele of rs139293 was associated with the altered expression of APOBEC3H and APOBEC3C and that the two genes were co-expressed in both tumor and adjacent normal tissues. These results indicate that genetic variants in APOBEC3H may contribute to lung cancer susceptibility in Chinese population.