Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population
Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population
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4q21、4q23 和 12q24 的遗传变异与中国人群食管鳞状细胞癌风险相关
DOI：
10.1007/s00439-013-1276-5
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发表时间：
2013-06-01
期刊：
影响因子：
5.3
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
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作者：
Gao, Yong;He, Yisha;Shen, Hongbing
最近发表的一项欧洲人群全基因组关联研究（GWAS）确定了4 q21、4 q23和12 q24上的几个位点与上呼吸消化道（UADT）癌症（包括食管鳞状细胞癌（ESCC））的风险相关。在本研究中，我们在中国人群中进行了一项病例对照研究，包括2，139例ESCC病例和2，273例对照，以评估6种已报道的单核苷酸多态性（SNP）（rs 1494961，rs 1229984，rs 1789924，rs 971074，rs671和rs 4767364）与ESCC风险的关系。我们发现4个SNPs与ESCC的风险显著相关，包括4 q21处HEL 308中的rs 1494961 [比值比（OR）= 1.15，95%置信区间（CI）= 1.05-1.26]，4 q23处ADH 1Bat中的rs 1229984 [OR = 1.15，95% CI = 1.05-1.26（OR = 1.24，95%CI = 1.13-1.36），rs 1789924与ADH 1Cat 4 q23接近（OR = 1.20，95%CI = 1.03-1.39），rs671与ALDH 2Cat 12 q24接近（OR = 0.83，95%CI = 0.75-0.91）。这四个SNP的联合分析显示，对于具有不同风险等位基因数量的个体，ESCC风险具有显著的等位基因剂量效应（Ptrend = 2.23 × 10−11）。与携带“0-2”危险等位基因的个体相比，携带“3”、“4”和“5或5以上”危险等位基因的个体发生ESCC的危险性分别为1.42、1.66和1.76倍。因此，我们的研究结果表明，4 q21的rs 1494961，4 q23的rs 1229984和rs 1789924，以及12 q24的rs671可以作为中国人群ESCC易感性的遗传标记。
A recently published genome-wide association study (GWAS) in European populations identified several loci at 4q21, 4q23 and 12q24 that were associated with risk of upper aerodigestive tract (UADT) cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we conducted a case–control study in a Chinese population including 2,139 ESCC cases and 2,273 controls to evaluate the associations of six reported single nucleotide polymorphisms (SNPs) (rs1494961, rs1229984, rs1789924, rs971074, rs671 and rs4767364) with risk of ESCC. We found significant association with risk of ESCC for four SNPs, including rs1494961 inHEL308at 4q21 [odds ratio (OR) = 1.15, 95 % confidence interval (CI) = 1.05–1.26], rs1229984 inADH1Bat 4q23 (OR = 1.24, 95 % CI = 1.13–1.36) and rs1789924 nearADH1Cat 4q23 (OR = 1.20, 95 % CI = 1.03-1.39), and rs671 inALDH2at 12q24 (OR = 0.83, 95 % CI = 0.75–0.91). Combined analysis of these four SNPs showed a significant allele-dosage effect on ESCC risk for individuals with different number of risk alleles (Ptrend = 2.23 × 10−11). Compared with individuals with “0–2” risk allele, those carrying “3”, “4” or “5 or more” risk alleles had 1.42-, 1.66-, or 1.76-fold risk of ESCC, respectively. Thus, our findings indicate that rs1494961 at 4q21, rs1229984 and rs1789924 at 4q23, and rs671 at 12q24 may be used as genetic biomarkers for ESCC susceptibility in Chinese population.