The genotype of ribonucleotidereductase M1 -269C > A is associated with the response to platinum-based chemotherapy and as a prognostic biomarker in advanced nonsmall cell lung cancer.
OBJECTIVE
Genetic polymorphisms of ribonucleotidereductase M1 (RRM1) was a DNA repair gene, which may affect patients' response to platinum-based chemotherapy or gemcitabine-based chemotherapy. We retrospectively assessed whether single nucleotide polymorphisms (SNPs) of RRM1 can be used to predict overall survival (OS), progression free survival and response in nonsmall cell lung cancer (NSCLC) patients treated with platinum-based regimens as first-line chemotherapy.


METHODS
The genotypes of four tagSNPs (RRM1 -316C > A, RRM1 -269C > A, RRM1 -702G > A and RRM1 -585T > G) were determined by SNaPshot detection technology and sequencing approaches in 184 advanced NSCLC patients by using peripheral blood.


RESULTS
The overall response rate for 178 patients was 40.2% and the disease control rate was 90.2%. In patients who had ever smoked, a significant correlation was observed between the genotype of RRM1 -269C > A and response (P = 0.046). There was a significant difference in response according to the genotype of RRM1 -702G > A (P = 0.043). Using Log-rank test, we found that patients with the allelotype (CC) of RRM1 -269C > A had a shorter OS (P = 0.006) than the allelotype (CA + AA).


CONCLUSIONS
The genotype of RRM1 -269C > A was significantly associated with platinum-based chemotherapy sensitivity in smoking patients and can be used to predict OS in advanced NSCLC patients who received platinum-based chemotherapy or gemcitabine-based chemotherapy. And the genotype of RRM1 -702G > A can serve as a biomarker for chemotherapy sensitivity in advanced NSCLC patients.
Xiao-Ling
XL
Xu
Yi-Ping
YP
Zhang
Yun
Y
Fang
Dan
D
Su
Wei
W
Chen
Jian-Guo
JG
Feng
Zhu-Peng
ZP
Li
Key Laboratory on Diagnosis and Treatment Technology on Thoracic Cancer, Zhejiang Cancer Hospital, Zhejiang Cancer Research Institute, Hangzhou 310022, Zhejiang Province; Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China.
Wei-Min
WM
Mao
D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D012307:Risk Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D010984:Platinum; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase