Ribonucleotide Reductase M1 Gene Polymorphism And Non-small Cell Lung Cancer, Platinum Chemotherapy Sensitivity Relationship

Objective:RRM1 encodes the regulatory M1 subunit of ribonucleotide reductase(RR).The M1 subunit(RRM1)controls substrate specificity and globle on/off enzyme activity,so it is the necessary part of the RR function.Ribonucleotide reductase catalyses the rate limiting step of deoxyribonucleotide formation,and it is crucially important in DNA synthesis and repair.This study is to investigate the relationship between polymorphisms of RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell cancer through detecting RRM1 genotypes by PCR-RFLP.Methods:214 histological confirmed patients with non-small lung cancer were analyzed.All patients were treated with platinum-based chemotherapy.PCR-RFLP was used to determine the promoter genotypes of RRM1 and to analyze the relationship between polymorphisms of RRM1 gene and patients' sensitivity to chemotherapy.Results:â‘ Among all cases,the frequencies of RR37C/C,C/A and A/A genotypes are 116(54.46%),87(40.85%)and10(4.69%)respectively;the frequencies of RR524 C/C,C/T and T/T gentypes are 25(11.68%),89(41.59%)and 100(46.73%) respectively.The overall response rate of chemotherapy(CR+PR)is 44.4%.â‘¡By analyzing the relationships of RR37AC polymorphisms as well as RR524CT polymorphisms to the sensitivity to platinum-based chemotherapy in non-small cell cancer,the patients' response rates of chemotherapy with RR37C/C,C/A and A/A genotypes are 44.83%,45.98%and 30.00%respectively.There is no statistically significant difference(x~2=0.928,p=0.629),After adjusting sex,age,stage,pathology and chemthery program,OR is 0.68(95%CI:0.16-2.85). The response rate to therapy among patients with RR524C/C,C/T and T/T genotypes are 24.00%,51.69%and 43.00%,with statistically significant difference(x~2=6.179,p=0.046). Further analysis shows that the response rates of patients with RR524 C/T and T/T genotype are significantly higher than those with RR524 C/C genotype(x~2=7.12,p=0.0076),(adjusted OR=2.70,95%CI:0.98-7.41).Compared with RR524C/C allele,patients with RR524T allele have a 2.7-fold sensitivity to platinum-based chemotherapy.â‘¢The incidence rate of increased ALT in RR37A/A genotype is significantly higher than C/C and C/A genotypes (x~2=7.795,p=0.02).Other toxicity has no significant difference.Conclusions:The polymorphisms of RR524CT may be associatated with the sensitivity to platinum-based chemotherapy in non-small cell lung cancer.Detection of RRM1 genotypes may indicate the sensitivity of NSCLC patients and it is valuable as a guideline to platinum-based chemotherapy.