title: Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations.
abstract: DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P(trend) = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P(trend) = 0.003) as well as for 261 subjects with different ethnicities (P(trend) = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Qiu
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Wang
authors.forename: Rui-Xi
authors.initials: RX
authors.lastname: Hua
authors.forename: Ruo-Xin
authors.initials: RX
authors.lastname: Zhang
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Ya-Nong
authors.initials: YN
authors.lastname: Wang
authors.forename: Meng-Hong
authors.initials: MH
authors.lastname: Sun
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhou
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Yang
authors.forename: Jiu-Cun
authors.initials: JC
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002681:China; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060148:HapMap Project; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000208:ethnology* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5