[Genetic polymorphisms in methylenetetrahydrofolate reductase and clinical response to chemotherapy in non-small cell lung cancer].

Abstract

BACKGROUND:

Methylenetetrahydrofolate reductase (MTHFR) plays an important role in metabolism of folate and DNA methylation. In vitro, many studies have demonstrated that abnormal methylation of some genes may affect the sensitivity of tumor cells to cytotoxic drugs and agents interfering with DNA synthesis. The aim of this study is to investigate the relationship between genetic polymorphisms of MTHFR C677T or A1298C and the response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC).

METHODS:

A total of 97 patients with NSCLC were analyzed. MTHFR genotypes were detected in all the patients by PCR-RFLP method. All the patients were treated with platinum-based chemotherapy.

RESULTS:

(1) Out of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 34.0%, 50.5% and 15.5%, respectively, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotypes were 64.6%, 29.2% and 6.3%, respectively. The overall response rate (complete and partial response) to platinum-based chemotherapy was 39.2%. (2) No significant difference in response rate to chemotherapy was observed according to the MTHFR C677T or A1298C genotypes. However, MTHFR C677T and A1298C polymorphisms showed a synergic effect on chemotherapeutic efficacy, the response rate of patients with MTHFR C677T T allele and A1298C A/A genotype (51.1%) was significantly higher than those with MTHFR C677T C/T and A1298C C allele (12.5%)(P=0.007, OR=7.30, 95% CI: 1.34-52.47).

CONCLUSIONS:

The results suggest that the synergic effect between MTHFR C677T and A1298C polymorphisms is associated with clinical response to platinum-based chemotherapy. Detection of MTHFR genotypes may indicate the sensitivity of NSCLC patients to platinum-based chemotherapy.

• Authors: Meiqi Shi, Changming Gao, Jianzhong Wu, Jifeng Feng, Haixia Cao, Jianwei Lu, Lin Xu
• Journal: Zhongguo fei ai za zhi = Chinese journal of lung cancer (Zhongguo Fei Ai Za Zhi) Vol. 9 Issue 6 Pg. 519-24 (Dec 20 2006) ISSN: 1009-3419 [Print] China
• PMID: 21182814 (Publication Type: English Abstract, Journal Article)