Ji Yong Bae, Lee Seung Hwan, Kim Kyung Rae, Park Chul Won, Song Chang Myeon, Park Byung Lae, Shin Hyoung Doo, Tae Kyung
Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-792, Korea.
Tumour Biol. 2015 Jun;36(6):4387-96. doi: 10.1007/s13277-015-3078-y. Epub 2015 Jan 21.
Alcohol consumption is one of the major risk factors for head and neck squamous cell carcinoma (HNSCC), and the alcohol dehydrogenase (ADH) family proteins are key enzymes in ethanol metabolism. We examined the associations between single nucleotide polymorphisms (SNPs) of ADH1B and ADH1C and the risk of HNSCC. We analyzed six SNPS of ADH1B, namely -992C > G, -957C > A, +3170A>G, +3377G>T, +3491G>A, and +13543A>G, and five SNPs of ADH1C, namely -1064C>T, -325G>C, +5702A>G, +7462T>C, and +13044A>G, in 260 Korean HNSCC patients and 330 controls, using single base extension and the TaqMan assay. The odds ratios (ORs) and 95 % confidence intervals (95 % CIs) of the CG and GG genotypes of ADH1B -992C>G, the AA genotype of -957C>A, the GG genotype of +3170A>G, the GA genotype of +3491G>A, and +13543A>G were 0.51 (0.32-0.82), 0.63 (0.42-0.94), 1.84 (1.13-2.99), 1.77 (1.15-2.73), 2.34 (1.44-3.79), and 2.21 (1.23-3.95), respectively. The ORs of ADH1C +13044A>G were 1.94 (1.01-3.71) and 1.97 (1.05-3.71) in the dominant and co-dominant models, respectively. The ORs of the GC genotype of ADH1C -325G>C and the AG genotype of +5702A>G were 2.52 (1.51-4.21) and 2.43 (1.36-4.32), respectively. ADH1B +3170A>G and ADH1C +13044A>G were in strong linkage disequilibrium with the other SNPs of ADH1B and ADH1C, respectively. There were gene-environment interactions between ADH1B +3170A>G and ADH1C +13044A>G and alcohol consumption and smoking. ADH1B +3170A>G and ADH1C +13044A>G SNPs are associated with an increased risk of HNSCC, and they could be used as biomarkers for the high-risk group of HNSCC in Koreans.
饮酒是头颈部鳞状细胞癌(HNSCC)的主要危险因素之一,而酒精脱氢酶(ADH)家族蛋白是乙醇代谢的关键酶。我们研究了ADH1B和ADH1C的单核苷酸多态性(SNP)与HNSCC风险之间的关联。我们使用单碱基延伸和TaqMan分析方法,对260例韩国HNSCC患者和330例对照者分析了ADH1B的6个SNP,即-992C>G、-957C>A、+3170A>G、+3377G>T、+3491G>A和+13543A>G,以及ADH1C的5个SNP,即-1064C>T、-325G>C、+5702A>G、+7462T>C和+13044A>G。ADH1B -992C>G的CG和GG基因型、-957C>A的AA基因型、+3170A>G的GG基因型、+3491G>A的GA基因型以及+13543A>G的比值比(OR)和95%置信区间(95%CI)分别为0.51(0.32 - 0.82)、0.63(0.42 - 0.94)、1.84(1.13 - 2.99)、1.77(1.15 - 2.73)、2.34(1.44 - 3.79)和2.21(1.23 - 3.95)。ADH1C +13044A>G在显性模型和共显性模型中的OR分别为1.94(1.01 - 3.71)和1.97(1.05 - 3.71)。ADH1C -325G>C的GC基因型和+5702A>G的AG基因型的OR分别为2.52(1.51 - 4.21)和2.43(1.36 - 4.32)。ADH1B +3170A>G和ADH1C +13044A>G分别与ADH1B和ADH1C的其他SNP处于强连锁不平衡状态。ADH1B +3170A>G和ADH1C +13044A>G与饮酒和吸烟之间存在基因 - 环境相互作用。ADH1B +3170A>G和ADH1C +13044A>G SNP与HNSCC风险增加相关,它们可作为韩国HNSCC高危人群的生物标志物。