Genetic variants of NBS1 predict clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer in Chinese.
OBJECTIVE
NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy.


METHODS
Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS.


RESULTS
Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39).


CONCLUSIONS
Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jia-Li
JL
Xu
Ling-Min
LM
Hu
Ming-De
MD
Huang
Wan
W
Zhao
Yong-Mei
YM
Yin
Zhi-Bin
ZB
Hu
Hong-Xia
HX
Ma
Hong-Bing
HB
Shen
Yong-Qian
YQ
Shu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D016190:Carboplatin / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China; D002945:Cisplatin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D016190:Carboplatin; D002945:Cisplatin