Genetic Susceptibility to Lung Adenocarcinoma

Abstract

Lung adenocarcinoma (LADC) is the most common histological type of lung cancer and its incidence is increasing worldwide. Genetic polymorphisms, including single nucleotide polymorphisms (SNPs), underlie inter-individual differences in cancer susceptibility, and genetic loci for LADC risk have been identified by genome-wide association studies (GWAS) and candidate gene association studies. Recently, three GWAS of LADC and subsequent pooled GWAS analyses identified genetic susceptibility variants on chromosome 15q25 (CHRNA), 5p15 (TERT), 3q28 (TP63), 6p21 (BAT3-MSH2 and BTNL2), and 17q.24 (BPTF). SNPs in TERT and TP63 are associated with increased risk for LADC in both never-smokers and smokers, whereas those in CHRNA are associated with increased risk of lung cancer irrespective of histological type. However, the risk alleles for CHRNA SNPs are rare in Asian populations, including Japanese. The association of 5p15 and 3q28 variants with increased risk of LADC was validated in both European and Asian populations; however, strength of association with LADC risk seems different by ethnicity. The association of SNPs in BTNL2 and BPTF with LADC risk was replicated in one study. On the other hand, significant associations of functional variants in DNA repair and metabolic genes have not been reported in lung cancer GWAS. Here, we review previously reported GWAS and candidate gene analyses and discuss identified genetic factors for LADC risk, which may be useful for early detection or prevention of LADC.