title: The genetic variations in DNA repair genes ERCC2 and XRCC1 were associated with the overall survival of advanced non-small-cell lung cancer patients.
abstract: It was reported that DNA repair can confer cancer cell resistance to therapeutic treatments by activating antiapoptotic cellular defense. We hypothesized that genetic variants of DNA repair genes may be associated with lung cancer prognosis. Seventeen tagging single-nucleotide polymorphism (tagSNPs) selected from 12 DNA repair genes were genotyped in 280 advanced non-small-cell lung cancer (NSCLC) patients by TaqMan assay. The associations of these SNPs and overall survival of advanced NSCLC patients were investigated. Advanced NSCLC patients carrying ERCC2 rs50872 CT+TT genotypes had significantly longer median survival time (MST) and decreased death risk than patients with rs50872 CC genotype [log-rank P = 0.031; adjusted HR(95% CI) = 0.73 (0.55-0.98), P = 0.033]. These effects were mainly seen among younger patients (≤65 years old) [HR(95% CI) = 0.57 (0.37-0.87), P = 0.010], patients without surgery [HR(95% CI) = 0.68 (0.47-0.98), P = 0.036] but with chemotherapy [HR(95% CI) = 0.64 (0.46-0.91), P = 0.012] or radiotherapy [HR(95% CI) = 0.58 (0.38-0.89), P = 0.013]. Meanwhile, compared to advanced NSCLC patients with rs25487 GG genotype, patients carrying XRCC1 rs25487 GA+AA genotypes had significantly shorter MST (MST = 11.7 vs. 16.7, log-rank P = 0.048). In addition, advanced NSCLC patients carrying the ERCC2 rs50872 CC in combination with XRCC1 rs25487 GA+AA genotype had the shortest MST (11.2 month) and highest death risk [HR(95% CI) = 1.70 (1.15-2.52), P = 0.008] when compared with those carrying rs50872 CT+TT and rs25487 GG genotype (MST = 22.0 month). The ERCC2 rs50872 T allele was associated with favorable but XRCC1 rs25487 A allele with bad survival for advanced NSCLC in Chinese population, which may offer novel biomarkers for predicting clinical outcomes.
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Suhan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, 430085, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yansen
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, 430085, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Meian
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, 430085, China. wgxuping@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. ghuan5011@hust.edu.cn.
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D004260:DNA Repair; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D000076105:X-ray Repair Cross Complementing Protein 1 / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: DNA repair; genetic variation; lung cancer; prognosis