title: Potentially functional variants in the core nucleotide excision repair genes predict survival in Japanese gastric cancer patients.
abstract: Functional genetic variants of DNA repair genes may alter the host DNA repair capacity, and thus influence efficiency of therapies. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in genes (i.e. ERCC1, XPA, XPC, XPD and XPG) involved in the nucleotide excision repair (NER) pathway in 496 Japanese gastric cancer patients, and assessed overall survival and recurrence-free survival. The combined effects of risk genotypes of these eight SNPs in Japanese patients were further replicated in 356 North-American gastric cancer patients. In Japanese patients, we found that the XPC rs2228000 TT genotype was associated with shorter overall survival [hazards ratio (HR) = 1.75, 95% confidence interval (95% CI) = 1.07-2.86] and recurrence-free survival (HR = 2.17, 95% CI = 1.19-3.95), compared with CC/CT genotypes, and the XPG rs17655 CC genotype was associated with shorter overall survival (HR = 1.60, 95% CI = 1.08-2.36), compared with GG/CG genotypes. The number of observed risk genotypes in the combined analysis was associated with shorter overall survival and recurrence-free survival in a dose-response manner (P(trend) = 0.006 and P(trend) < 0.000) in Japanese patients; specifically, compared with those with ≤1 risk genotypes, those with ≥2 risk genotypes showed markedly shorter overall survival (HR = 1.79, 95% CI = 1.18-2.70) and recurrence-free survival (HR = 2.80, 95% CI = 1.66-4.73). The association between ≥2 risk genotypes and shorter overall survival was not significant (HR = 1.26, 95% CI = 0.82-1.94) in North-American patients, but the trends were similar in these two groups of patients. These data show that functional SNPs in NER core genes may impact survival in Japanese gastric cancer patients.
authors.affiliation: Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China, Duke Cancer Institute, Duke University Medical Center, 905 Lasalle Street, Durham, NC 27710, USA, Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA, Department of Gastroenterological Surgery, St Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan and Department of Gastrointestinal Medical Oncology and Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yangkai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, 905 Lasalle Street, Durham, NC 27710, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, 905 Lasalle Street, Durham, NC 27710, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.affiliation: Department of Gastroenterological Surgery, St Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan and.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Onodera
authors.affiliation: Department of Gastroenterological Surgery, St Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan and.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterological Surgery, St Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan and.
authors.forename: Koyu
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Gastrointestinal Medical Oncology and.
authors.forename: Roopma
authors.initials: R
authors.lastname: Wadhwa
authors.affiliation: Department of Gastrointestinal Medical Oncology and.
authors.forename: Elena
authors.initials: E
authors.lastname: Elimova
authors.affiliation: Department of Gastrointestinal Medical Oncology and.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sudo
authors.affiliation: Department of Gastrointestinal Medical Oncology and.
authors.forename: Hironari
authors.initials: H
authors.lastname: Shiozaki
authors.affiliation: Department of Gastrointestinal Medical Oncology and.
authors.forename: Jeannelyn
authors.initials: J
authors.lastname: Estrella
authors.affiliation: Department of Gastrointestinal Medical Oncology and.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Gastrointestinal Medical Oncology and.
authors.forename: Shumei
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Tan
authors.affiliation: Department of Gastrointestinal Medical Oncology and jajani@mdanderson.org.
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, 905 Lasalle Street, Durham, NC 27710, USA, jajani@mdanderson.org qingyi.wei@duke.edu.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality; 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; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C086984:XPC protein, human