No association between XRCC1 polymorphisms and survival in non-small-cell lung cancer patients treated with platinum-based chemotherapy.
OBJECTIVE
genetic polymorphisms in DNA repair genes are thought to represent important determinants of platinum drug efficacy. The current study investigated whether single nucleotide polymorphisms (SNPs) in the X-ray repair cross complementing protein 1 (XRCC1) gene are associated with survival in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.


METHODS
a total of 199 platinum-treated patients with stage III-IV NSCLC were recruited. Overall survival (OS) and progression-free survival (PFS) according to genotypes and haplotypes were analyzed using Kaplan-Meier method and assessed by log-rank test. Hazard ratios (HRs) were calculated using Cox proportional hazards models by adjusting for clinical factors.


RESULTS
during the median 26.5 months of follow-up, 159 deaths occurred. Regarding XRCC1 Arg194Trp, Arg280His, and Arg399Gln genotypes, no significant effects on survival were observed, although the 280Arg/His genotype was associated with a borderline-significant higher median survival time (20.0 months for Arg/His versus 16.0 months for Arg/Arg; P = 0.131). Moreover, no significant association of haplotypes with survival was found.


CONCLUSIONS
this study showed no influence of the XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms on survival in advanced NSCLC patients with platinum-based chemotherapy.
Yuan
Peng
P
Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Liu
Li
L
Wu
Chen
C
Zhong
Rong
R
Yu
Dianke
D
Wu
Jing
J
Xu
Yihua
Y
Nie
Shaofa
S
Miao
Xiaoping
X
Sun
Yan
Y
Xu
Binghe
B
Lin
Dongxin
D
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D015996:Survival Rate; D000076105:X-ray Repair Cross Complementing Protein 1
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D017671:Platinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human