Functional Variant in 3′UTR of <i>FAM13A</i> Is Potentially Associated with Susceptibility and Survival of Lung Squamous Carcinoma

Abstract

<i>FAM13A</i> is associated with aging lung disease (primarily chronic obstructive pulmonary disorder and pulmonary fibrosis) and shows stable expression throughout lung development. However, a few systematic studies of <i>FAM13A</i> have been conducted to assess the pathogenesis of lung cancer, particularly susceptibility. We predicted that single-nucleotide polymorphisms (SNPs) in <i>FAM13A</i> may be associated with lung cancer development. We systematically selected five functional SNPs (rs2602120, rs3017895, rs9224, rs7657817, and rs3756050) and genotyped them with the Genesky proprietary improved Multiligase Detection Reaction multiplex SNP genotyping system in a case-control study of 626 lung cancer cases and 667 cancer-free controls. The functional effects of <i>FAM13A</i> and specific miRNAs (miRNA-22-5p and miRNA-1301-3p) were evaluated based on The Cancer Genome Atlas database. We found that rs9224 in the 3' untranslated region (UTR) of <i>FAM13A</i> was potentially associated with an increased risk of lung squamous carcinoma (LUSQ) (additive model: odds ratio = 1.47, 95% confidence interval = 1.04-2.07, <i>p</i> = 0.028). In addition, the results of expression quantitative trait loci analysis suggested that the rs9224 polymorphism affects the expression of <i>FAM13A</i> (<i>p</i> = 0.050) and miRNA-22-5p (<i>p</i> = 0.031) in LUSQ. Further, survival analysis indicated decreased overall survival in the presence of the variant alleles of rs9224 (<i>p</i> = 0.048). The present results indicate that variant genotypes of rs9224 in the <i>FAM13A</i> 3'UTR may modify LUSQ susceptibility by affecting the binding of miRNA-22-5p and predict a poor prognosis of patients with LUSQ.