title: Polymorphisms of MTHFR C677T and A1298C associated with survival in patients with colorectal cancer treated with 5-fluorouracil-based chemotherapy.
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.
authors.affiliation: School of Public Health, College of Public Health, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan. ccyeh@tmu.edu.tw.|Department of Public Health, College of Public Health, China Medical University, 91 Hsieh-Shih Road, Taichung, 404, Taiwan. ccyeh@tmu.edu.tw.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Yeh
authors.affiliation: School of Public Health, College of Public Health, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lai
authors.affiliation: Management Office for Health Data, China Medical University Hospital, 2 Yude Road, Taichung, 404, Taiwan.|Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, 91 Hsieh-Shih Road, Taichung, 404, Taiwan.
authors.forename: Shih-Ni
authors.initials: SN
authors.lastname: Chang
authors.affiliation: Department of Public Health, Chang Gung University, 259 Wen-Hwa 1st Road, Guieshan, 333, Taoyuan, Taiwan.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
authors.affiliation: Colorectal Section, Chang Gung Memorial Hospital, 5 Fusing Street, Guieshan, 333, Taoyuan, Taiwan.|School of Traditional Chinese Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Guieshan, 333, Taoyuan, Taiwan.
authors.forename: Reiping
authors.initials: R
authors.lastname: Tang
authors.affiliation: Management Office for Health Data, China Medical University Hospital, 2 Yude Road, Taichung, 404, Taiwan.|Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, 91 Hsieh-Shih Road, Taichung, 404, Taiwan.
authors.forename: Fung-Chang
authors.initials: FC
authors.lastname: Sung
authors.affiliation: Department of Industrial Management, National Taiwan University of Science and Technology, 43, Sec. 4, Keelung Road, Taipei, 106, Taiwan.
authors.forename: Yi-Kuei
authors.initials: YK
authors.lastname: Lin
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D012189:Retrospective Studies; D016019:Survival Analysis; D013624:Taiwan
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D005472:Fluorouracil
keywords: 5-Fluorouracil; Colorectal cancer; MTHFR; Overall survival; Polymorphisms