Chih-Ching Yeh1,2, Ching-Yu Lai3, Shih-Ni Chang4,5, Ling-Ling Hsieh6, Reiping Tang7,8, Fung-Chang Sung4,5, Yi-Kuei Lin9. 1. School of Public Health, College of Public Health, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan. ccyeh@tmu.edu.tw. 2. Department of Public Health, College of Public Health, China Medical University, 91 Hsieh-Shih Road, Taichung, 404, Taiwan. ccyeh@tmu.edu.tw. 3. School of Public Health, College of Public Health, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan. 4. Management Office for Health Data, China Medical University Hospital, 2 Yude Road, Taichung, 404, Taiwan. 5. Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, 91 Hsieh-Shih Road, Taichung, 404, Taiwan. 6. Department of Public Health, Chang Gung University, 259 Wen-Hwa 1st Road, Guieshan, 333, Taoyuan, Taiwan. 7. Colorectal Section, Chang Gung Memorial Hospital, 5 Fusing Street, Guieshan, 333, Taoyuan, Taiwan. 8. School of Traditional Chinese Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Guieshan, 333, Taoyuan, Taiwan. 9. Department of Industrial Management, National Taiwan University of Science and Technology, 43, Sec. 4, Keelung Road, Taipei, 106, Taiwan.
Abstract
BACKGROUND: This study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and survival of patients with colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy in Taiwan. METHODS: We genotyped MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) for 498 CRC patients treated with 5-FU-based chemotherapy after receiving surgery. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan-Meier curve. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MTHFR genotypes and survival. RESULTS: Overall survival (OS) was significantly longer in CRC patients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR 0.77; 95% CI 0.60-0.98). Although the MTHFR A1298C polymorphism was not associated with OS in CRC, this polymorphism was associated with significantly shorter OS in rectal cancer. Among rectal cancer patients, OS was shorter for patients with AC+CC genotypes than for those with the AA genotype (HR 1.95; 95% CI 1.35-2.83). In haplotype analysis, better OS was found for colon cancer patients carrying the MTHFR 677T-1298A haplotype (HR 0.73; 95% CI 0.55-0.97), but worse survival was linked to rectal cancer patients carrying the MTHFR 677C-1298C haplotype (HR 1.53; 95% CI 1.08-2.18). CONCLUSIONS: Our findings suggest that MTHFR genotypes provide prognostic information for CRC patients treated with 5-FU-based chemotherapy.
BACKGROUND: This study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and survival of patients with colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy in Taiwan. METHODS: We genotyped MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) for 498 CRCpatients treated with 5-FU-based chemotherapy after receiving surgery. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan-Meier curve. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MTHFR genotypes and survival. RESULTS: Overall survival (OS) was significantly longer in CRCpatients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR 0.77; 95% CI 0.60-0.98). Although the MTHFRA1298C polymorphism was not associated with OS in CRC, this polymorphism was associated with significantly shorter OS in rectal cancer. Among rectal cancerpatients, OS was shorter for patients with AC+CC genotypes than for those with the AA genotype (HR 1.95; 95% CI 1.35-2.83). In haplotype analysis, better OS was found for colon cancerpatients carrying the MTHFR 677T-1298A haplotype (HR 0.73; 95% CI 0.55-0.97), but worse survival was linked to rectal cancerpatients carrying the MTHFR 677C-1298C haplotype (HR 1.53; 95% CI 1.08-2.18). CONCLUSIONS: Our findings suggest that MTHFR genotypes provide prognostic information for CRCpatients treated with 5-FU-based chemotherapy.
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