Abstract
BACKGROUND: Abnormal glycosylation modification is closely related to the development and metastasis of cancers. As a carcinogen by the International Agency for Research on Cancer (IARC) of the WHO, areca nut lacked of combined effect' study with genetic factors related to lung cancer. The aim of this study was to investigate the combined effect of polymorphisms of glycosyltransferase family genes and behavioral factors on the susceptibility of lung cancer. METHODS: A case‒control study was conducted in Hainan, which included 428 patients with lung cancer and 428 cancer-free controls. Six single-nucleotide polymorphisms (SNPs) (FUT2 rs1047781, rs601338, FUT3 rs28362459, rs3745635, ST6Gal-I rs2239611 and MGAT5 rs34944508) were detected by the MassARRAY System. The association between these SNPs and the risk of lung cancer, clinicopathological characteristics, and combined effect of behavioral factors (areca nuts, cigarettes, alcohol) and genotypes on lung cancer were estimated using by logistic regression analysis. RESULTS: In this study, individuals with AA genotype in ST6Gal-I rs2239611 significantly increased lung cancer risk (OR(adj) = 2.077; 95%CI:1.191-3.624; P(adj) = 0.010), particularly in smokers (P(adj) = 0.038) and alcohol consumers (P(adj) = 0.049). FUT2 rs1047781 was associated with clinical stage (P(adj) = 0.047) and lymph node metastasis (P(adj) = 0.014). Significant gene-environment interactions were observed between behavioral factors (cigarette smoking, alcohol drinking, and betel quid chewing) and both FUT2 rs1047781 (P(adj) = 0.013) and ST6Gal-I rs2239611 (P(adj) = 0.047), collectively elevating lung cancer risk. CONCLUSION: ST6Gal-I rs2239611 was a potential genetic biomarker for lung cancer. Areca nut chewing, cigarette smoking, alcohol drinking interacts with glycosyltransferase gene polymorphisms (FUT2 rs1047781 and ST6Gal-I rs2239611), increasing lung cancer risk-a novel finding given the lack of prior studies on this combination.