AIMS: Genetic factors may contribute to individual differences in cancer susceptibility, drug efficacy and toxicity. This study was designed to investigate the effects of the polymorphisms of methylenetetrahydrofolate reductase 677 C→T (MTHFR 677 C→T), thymidylate synthase (TYMS 3R→2R),and methionine synthase 2756 A→G (MTR 2756 A→G) on the risk of lung cancer and response to platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC). MATERIALS & METHODS: We conducted a case-control study involving 438 NSCLC cases (including 101 follow-up cases) and 641 healthy controls in North China. RESULTS & CONCLUSION: Using a genetic model analysis, the polymorphism MTHFR 677 C→T showed a significantly increased risk for NSCLC in women but not in men, which was observed in the codominant model (CT vs CC adjusted odds ratio [OR] = 2.46; 95% confidence interval [CI]: 1.37-4.42; p = 0.003; TT vs CC adjusted OR: 2.04; 95% CI: 1.09-3.81; p = 0.03) and the dominant model (CT + TT vs CC adjusted OR: 2.30; 95% CI: 1.31-4.05; p = 0.004). In addition, we found that patients with the MTHFR 677 TT genotype showed a better response to platinum-based chemotherapy in the recessive model (TT vs CT + CC adjusted OR: 0.24; 95% CI: 0.09-0.68; p = 0.007), the generalized OR was 0.44 (0.22-0.88; p = 0.04). There were no significant associations of the polymorphisms of TYMS 3R→2R or MTR 2756 A→G with the risk of NSCLC or response to platinum-based chemotherapy in advanced NSCLC in any genetic model. Our results suggest that genetic polymorphisms of MTHFR 677 C→T may contribute to NSCLC development in Chinese women and could also influence treatment response for advanced NSCLC patients with platinum-based chemotherapy. Further studies with larger sample sizes are required to validate this association.
AIMS: Genetic factors may contribute to individual differences in cancer susceptibility, drug efficacy and toxicity. This study was designed to investigate the effects of the polymorphisms of methylenetetrahydrofolate reductase 677 C→T (MTHFR 677 C→T), thymidylate synthase (TYMS 3R→2R),and methionine synthase 2756 A→G (MTR 2756 A→G) on the risk of lung cancer and response to platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC). MATERIALS & METHODS: We conducted a case-control study involving 438 NSCLC cases (including 101 follow-up cases) and 641 healthy controls in North China. RESULTS & CONCLUSION: Using a genetic model analysis, the polymorphism MTHFR 677 C→T showed a significantly increased risk for NSCLC in women but not in men, which was observed in the codominant model (CT vs CC adjusted odds ratio [OR] = 2.46; 95% confidence interval [CI]: 1.37-4.42; p = 0.003; TT vs CC adjusted OR: 2.04; 95% CI: 1.09-3.81; p = 0.03) and the dominant model (CT + TT vs CC adjusted OR: 2.30; 95% CI: 1.31-4.05; p = 0.004). In addition, we found that patients with the MTHFR 677 TT genotype showed a better response to platinum-based chemotherapy in the recessive model (TT vs CT + CC adjusted OR: 0.24; 95% CI: 0.09-0.68; p = 0.007), the generalized OR was 0.44 (0.22-0.88; p = 0.04). There were no significant associations of the polymorphisms of TYMS 3R→2R or MTR 2756 A→G with the risk of NSCLC or response to platinum-based chemotherapy in advanced NSCLC in any genetic model. Our results suggest that genetic polymorphisms of MTHFR 677 C→T may contribute to NSCLC development in Chinese women and could also influence treatment response for advanced NSCLCpatients with platinum-based chemotherapy. Further studies with larger sample sizes are required to validate this association.
Authors: Kristina G Flores; Christine A Stidley; Amanda J Mackey; Maria A Picchi; Sally P Stabler; Jill M Siegfried; Tim Byers; Marianne Berwick; Steven A Belinsky; Shuguang Leng Journal: Carcinogenesis Date: 2012-06-04 Impact factor: 4.944
Authors: Yao Zhang; Guo Qiang Chen; Yong Ji; Bin Huang; Wei Sheng Shen; Li Chun Deng; Lei Xi; Xiang Ming Cao Journal: Mol Biol Rep Date: 2012-01-04 Impact factor: 2.316
Authors: F Aminkeng; C J D Ross; S R Rassekh; L R Brunham; J Sistonen; M-P Dube; M Ibrahim; T B Nyambo; S A Omar; A Froment; J-M Bodo; S Tishkoff; B C Carleton; M R Hayden Journal: Pharmacogenomics J Date: 2013-04-16 Impact factor: 3.550