Polymorphisms of the ribonucleotide reductase M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer

Feng, Ji-feng; Wu, Jian-zhong; Hu, Sai-nan; Gao, Chang-ming; Shi, Mei-qi; Lu, Zhu-hong; Sun, Xin-chen; Zhou, Jin-Rong; Chen, Bao-an

doi:10.1016/j.lungcan.2009.02.015

« Previous Next »Lung Cancer
Volume 66, Issue 3 , Pages 344-349, December 2009

Polymorphisms of the ribonucleotide reductase M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer

Ji-feng Feng
- School of Clinical Medical Science, Southeast University, 87 Dingjiaqiao Street, Nanjing 210009, PR China
- Department of Oncology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, PR China
Jian-zhong Wu
- Department of Oncology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, PR China
Sai-nan Hu
- Department of Oncology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, PR China
Chang-ming Gao
- Department of Oncology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, PR China
Mei-qi Shi
- Department of Oncology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, PR China
Zhu-hong Lu
- Laboratory of Molecular and Biomolecular Electronics, Southeast University, Nanjing 210006, PR China
Xin-chen Sun
- School of Clinical Medical Science, Southeast University, 87 Dingjiaqiao Street, Nanjing 210009, PR China
Jin-Rong Zhou
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
Bao-an Chen
- School of Clinical Medical Science, Southeast University, 87 Dingjiaqiao Street, Nanjing 210009, PR China
- Corresponding author. Tel.: +86 25 83272006; fax: +86 25 83272011.

Received 4 December 2008; received in revised form 16 February 2009; accepted 19 February 2009. published online 23 March 2009.

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.