title: Potentially functional polymorphisms in the ERCC2 gene and risk of esophageal squamous cell carcinoma in Chinese populations.
abstract: ERCC2 is indispensable for nucleotide excision repair pathway, and its functional polymorphisms may be associated with cancer risk. In a large case-control study of 1126 esophageal squamous cell carcinomas (ESCC) patients and 1131 controls, we genotyped two SNPs in ERCC2 (rs238406 G > T and rs13181 T > G) and assessed their associations with ESCC risk. We found a significantly elevated ESCC risk associated with the rs238406 T variant genotypes (adjusted OR = 1.30 and 1.24, 95% CI = 1.02-1.66 and 1.03-1.49 for TG and TG/TT, respectively, compared with GG), particularly in the subgroup of those smoked more than 16 pack-years. Multivariate logistic regression analysis suggested a possible multiplicative gene-environment interaction between rs238406 genotypes and smoking (Pinteraction = 0.026) on ESCC risk. Although no significant risk associations were observed for rs13181, further mini meta-analysis with our and 18 other published studies of 5,012 cases and 8,238 controls found evidence of an association between the rs13181 variant G allele and esophageal cancer risk (TG/GG vs. TT, OR = 1.17; 95% CI = 1.02-1.33). Interestingly, we consistently found a significant correlation between variant genotypes of these two SNPs and ERCC2 mRNA expression. These findings suggest that potentially functional SNPs in ERCC2 may contribute to ESCC risk.
authors.affiliation: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China [3] Department of Oncology, Xin Hua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Zhu
authors.affiliation: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: MengYun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
authors.forename: Meng-Hong
authors.initials: MH
authors.lastname: Sun
authors.affiliation: 1] State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China [2] Fudan-Taizhou Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: 1] State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China [2] Fudan-Taizhou Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1] State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China [2] Fudan-Taizhou Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: 1] State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China [2] Fudan-Taizhou Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, China.
authors.forename: Jiu-Cun
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Department of Oncology, Xin Hua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Leizhen
authors.initials: L
authors.lastname: Zheng
authors.affiliation: 1] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China [2] Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Xiang
authors.affiliation: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China [2] Duke Cancer Institute, Duke University Medical Center, 10 Bryn Searle Dr., Durham, NC 27710, USA.
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics*; D002461:Cell Line, Transformed; D002681:China / Q000453:epidemiology; D004260:DNA Repair / Q000235:genetics; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis; D012306:Risk; D012907:Smoking / Q000453:epidemiology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D010651:Phenylalanine Hydroxylase; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human