Relationship between esophageal squamous cell carcinoma risk and alcohol-related ALDH2 and ADH1B polymorphisms: Evidence from a meta-analysis and Mendelian randomization analysis

作者全名："Zhang, Biao; Peng, Yu-Hui; Luo, Yun; Hong, Chao-Qun; Lin, Yi-Wei; Zhang, Yu-Ling; Xu, Yi-Wei; Su, Xue-Fen; Wu, Fang-Cai"

作者地址："[Zhang, Biao; Peng, Yu-Hui; Luo, Yun; Lin, Yi-Wei; Xu, Yi-Wei] Shantou Univ, Canc Hosp, Dept Clin Lab Med, Med Coll, Shantou, Peoples R China; [Zhang, Biao] Bin Hai Wan Cent Hosp Dongguan, Dept Prevent Med, Dongguan, Peoples R China; [Zhang, Biao; Peng, Yu-Hui; Luo, Yun; Hong, Chao-Qun; Lin, Yi-Wei; Xu, Yi-Wei; Su, Xue-Fen; Wu, Fang-Cai] Shantou Univ, Med Coll, Esophageal Canc Prevent & Control Res Ctr, Canc Hosp, Shantou, Peoples R China; [Peng, Yu-Hui; Lin, Yi-Wei; Xu, Yi-Wei] Shantou Univ, Precis Med Res Ctr, Med Coll, Shantou, Peoples R China; [Luo, Yun] Chongqing Med Univ, Yongchuan Hosp, Chongqing, Peoples R China; [Zhang, Yu-Ling] Shantou Univ, Res Inst Clin Pharm, Med Coll, Shantou, Peoples R China; [Wu, Fang-Cai] Shantou Univ, Dept Radiat Oncol, Canc Hosp, Med Coll, Shantou, Peoples R China; [Xu, Yi-Wei; Su, Xue-Fen; Wu, Fang-Cai] 7 Raoping Rd, Shantou 515041, Peoples R China"

通信作者："Xu, YW; Su, XF; Wu, FC (通讯作者)，7 Raoping Rd, Shantou 515041, Peoples R China."

来源：CANCER MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001077798900001

JCR分区：Q2

影响因子：2.9

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：ADH1B; ALDH2; epidemiological evidence; esophageal squamous cell carcinoma; meta-analysis

摘要："Background: Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta-analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence.Methods: We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false-positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I-2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen-2 were analyzed for functional annotations.Results: Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50-0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70-3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21-1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71-2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52-3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk.Conclusions: The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC."

基金机构：We thank Professor Stanley Li Lin and Dr. Frieda Law for manuscript revision and edition.

基金资助正文：We thank Professor Stanley Li Lin and Dr. Frieda Law for manuscript revision and edition.