title: Genetic polymorphism of XRCC1 correlated with response to oxaliplatin-based chemotherapy in advanced colorectal cancer.
abstract: To examine the association between genetic polymorphisms of XRCC1 Arg399Gln(G→A) and response to oxaliplatin-based chemotherapy in advanced colorectal cancer. XRCC1 genotypes of totally 99 patients(37 stage III, 62 stage IV)with advanced colorectal cancer treated with oxaliplatin-based chemotherapy were detected by TaqMan-MGB probe allelic discrimination method. And clinical response of 62 patients in stage IVafter 2 to 3 cycles of chemotherapy were evaluated. Also time to progress (TTP) of all patients were evaluated. Of the genotype frequencies in all patients, up to 52.53 % were G/G genotype, 9.09 % were A/A genotype, and 38.38 % were G/A genotype. The response rate (CR+PR) of 62 patients in stage IV was 61.29 % (19/31). Patients with G/G genotype showed enhanced respond to chemotherapy compared to those with G/A+A/A (x(2) = 5.6, P = 0.029; OR = 3.845, 95 %CI = 1.231 ~ 12.01, P = 0.018). Individuals with the G/G genotype had a TTP of 10.0 (8.88-11.12) months, those with the G/A+A/A genotype had an TTP of 5.0(4.26-5.74) months. The log-rank test was marginally significant (x(2) = 29.20, P < 0.01). The Cox proportional hazards model, adjusted for stage, performance status, and chemotherapy regimen, showed that only XRCC1 G/G genotypes increases the OR significantly (OR = 3.555; 95 % CI, 2.119 ~ 5.963; P < 0.01). The results suggest that XRCC1 Arg399Gln polymorphisms is associated with the response to oxaliplatin-based chemotherapy and time to progression in advanced colorectal cancer in Chinese population. It is proposed that the XRCC1 Arg399Gln polymorphism should be routinely detected to screen patients who are more likely benefit from oxaliplatin-based treatment.
authors.affiliation: The Affiliated Hospital of Qingdao University Medical College, CN-Qingdao, 266003, People's Republic of China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Lv
authors.forename: Qicai
authors.initials: Q
authors.lastname: Li
authors.forename: Wengsheng
authors.initials: W
authors.lastname: Qiu
authors.forename: Jinyu
authors.initials: J
authors.lastname: Xiang
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wei
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.forename: Aihua
authors.initials: A
authors.lastname: Sui
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil