槟榔、香烟、酒精与糖基转移酶家族基因单核苷酸多态性对中国海南肺癌发生发展的联合作用
Combined effect of areca nut, cigarettes, alcohol and SNPs in glycosyltransferase family genes on lung cancer development in Hainan, China.
作者信息
Kuang Shicheng, Xiao Sha, Zhou Jing, Liu Lirong, Li Na, Ding Yipeng, Lyu Pengfei, Zhu Chaoyong, Xue Ping
机构信息
Department of Pharmacy, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
School of Public Health, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, Hainan, 571199, People's Republic of China.
出版信息
BMC Cancer. 2025 Apr 30;25(1):814. doi: 10.1186/s12885-025-14088-x.
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 = 2.077; 95%CI:1.191-3.624; P = 0.010), particularly in smokers (P = 0.038) and alcohol consumers (P = 0.049). FUT2 rs1047781 was associated with clinical stage (P = 0.047) and lymph node metastasis (P = 0.014). Significant gene-environment interactions were observed between behavioral factors (cigarette smoking, alcohol drinking, and betel quid chewing) and both FUT2 rs1047781 (P = 0.013) and ST6Gal-I rs2239611 (P = 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.
背景
异常糖基化修饰与癌症的发生和转移密切相关。槟榔作为世界卫生组织国际癌症研究机构（IARC）认定的致癌物，缺乏与肺癌相关遗传因素的“联合效应”研究。本研究旨在探讨糖基转移酶家族基因多态性与行为因素对肺癌易感性的联合效应。
方法
在海南进行了一项病例对照研究，纳入428例肺癌患者和428例无癌对照。采用MassARRAY系统检测6个单核苷酸多态性（SNP）（FUT2 rs1047781、rs601338，FUT3 rs28362459、rs3745635，ST6Gal-I rs2239611和MGAT5 rs34944508）。通过逻辑回归分析评估这些SNP与肺癌风险、临床病理特征以及行为因素（槟榔、香烟、酒精）和基因型对肺癌的联合效应之间的关联。
结果
在本研究中，ST6Gal-I rs2239611中AA基因型个体的肺癌风险显著增加（OR = 2.077；95%CI：1.191 - 3.624；P = 0.010），尤其是在吸烟者（P = 0.038）和饮酒者（P = 0.049）中。FUT2 rs1047781与临床分期（P = 0.047）和淋巴结转移（P = 0.014）相关。行为因素（吸烟、饮酒和嚼槟榔）与FUT2 rs1047781（P = 0.013）和ST6Gal-I rs2239611（P = 0.047）之间均观察到显著的基因-环境相互作用，共同增加了肺癌风险。
结论
ST6Gal-I rs2239611是肺癌的潜在遗传生物标志物。嚼槟榔、吸烟、饮酒与糖基转移酶基因多态性（FUT2 rs1047781和ST6Gal-I rs2239611）相互作用，增加肺癌风险——鉴于此前缺乏对此组合的研究，这是一个新发现。
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