title: Polymorphisms of the ribonucleotide reductase M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer.
abstract: Ribonucleotide reductase catalyzes the rate limiting step of deoxyribonucleotide formation, a crucially important step in DNA synthesis and repair. The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and global on/off enzyme activity. Despite recent research progress, the role of RRM1 in lung cancer sensitivity to chemotherapeutics remains to be elucidated. This study was to investigate the relationship between polymorphisms of the RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Genomic DNA samples from 214 NSCLC patients treated with platinum-based chemotherapy were used to determine the RRM1 promoter allelotypes. The RR37CC-RR524TT was the most frequent allelotype (38.50%), followed by RR37AC-RR524CT (26.76%) and RR37CC-RR524CT (14.95%). The average response rate for chemotherapy was 44.4%. The response rates to the treatment regimens in the RR37CC-RR524TT, RR37AC-RR524CT and RR37CC-RR524CT allelotypes were 43.9%, 52.6%, and 51.6%, respectively. The response rates to therapy among patients with RRM1 (-)524 allelotypes were significantly different (p=0.046), whereas that among patients with RRM1 (-)37 allelotypes were not significant. Further analysis showed that the response rate in the patients with RR524CT allelotype (52.3%) was the highest, compared with that with RR37CC-RR524TT allelotype (43.9%, p=0.28), or the Others (RR524CC and RR37AC-RR524TT, 30.2%, p=0.02). Our results suggest that the RR524CT allelotype may be associated with an increased sensitivity to platinum-based chemotherapy in NSCLC. Further research on determining RR524CT as a clinical marker for predicting response to platinum-based therapy in NSCLC patients is warranted.
authors.affiliation: School of Clinical Medical Science, Southeast University, 87 Dingjiaqiao Street, Nanjing 210009, PR China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Feng
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Wu
authors.forename: Sai-Nan
authors.initials: SN
authors.lastname: Hu
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Gao
authors.forename: Mei-Qi
authors.initials: MQ
authors.lastname: Shi
authors.forename: Zhu-Hong
authors.initials: ZH
authors.lastname: Lu
authors.forename: Xin-Chen
authors.initials: XC
authors.lastname: Sun
authors.forename: Jin-Rong
authors.initials: JR
authors.lastname: Zhou
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017671:Platinum Compounds / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D054316:Biomarkers, Pharmacological; D017671:Platinum Compounds; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase