title: Functional BCL-2 regulatory genetic variants contribute to susceptibility of esophageal squamous cell carcinoma.
abstract: B-cell lymphoma-2 (BCL-2) prevents apoptosis and its overexpression could promote cancer cell survival. Multiple functional BCL-2 genetic polymorphisms, such as rs2279115, rs1801018 and rs1564483, have been identified previously and might be involved in cancer development through deregulating BCL-2 expression. Therefore, we examined associations between these three polymorphisms and esophageal squamous cell carcinoma (ESCC) susceptibility as well as its biological function in vivo. Genotypes were determined in two independent case-control sets consisted of 1588 ESCC patients and 1600 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. The impact of the rs2279115 polymorphism on BCL-2 expression was detected using esophagus tissues. Our results demonstrated that the BCL-2 rs2279115 AA genotype was significantly associated with decreased ESCC risk compared with the CC genotype (OR = 0.72, 95% CI = 0.57-0.90, P = 0.005), especially in nonsmokers (OR = 0.42, 95% CI = 0.29-0.59, P = 0.001) or nondrinkers (OR = 0.44, 95% CI = 0.32-0.62, P =  .002). Genotype-phenotype correlation studies demonstrated that subjects with the rs2279115 CA and AA genotypes had a statistically significant decrease of BCL-2 mRNA expression compared to the CC genotype in both normal and cancerous esophagus tissues. Our results indicate that the BCL-2 rs2279115 polymorphism contributes to ESCC susceptibility in Chinese populations.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Gastrointestinal Surgery, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Jinyun
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Zhiqiong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects
chemical_list: C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2