title: The prognostic significance of polymorphisms in hMLH1/hMSH2 for colorectal cancer.
abstract: We aimed to investigate the associations between single-nucleotide polymorphisms (SNPs) in two mismatch repair genes (hMLH1 and hMSH2) and colorectal cancer (CRC) prognosis in Northeast China. We genotyped 387 patients for 10 SNPs in hMLH1 and hMSH2, using polymerase chain reaction restriction fragment length polymorphism approach. Associations between genotypes and overall survival (OS) were estimated using hazard ratios (HRs) and 95 % confidence intervals (CIs). Two SNPs of hMLH1 (hMLH1 -93G>A and IVS3-1403A>T) were significantly associated with OS of CRC in dominant model and recessive model, respectively. For hMLH1 -93G>A, the adjusted HR equaled 0.66 (95 % CI 0.45-0.99, p = 0.04). As for hMLH1 IVS3-1403A>T, the adjusted HR equaled 1.90 (95 % CI 1.14-3.17, p = 0.01). When stratified by tumor location, hMLH1 -93G>A and IVS3-1403A>T were associated with colon cancer survival (for hMLH1 -93G>A, AA+AG vs. GG, HRadj = 0.34, 95 % CI 0.17-0.68, p < 0.01; for hMLH1 IVS3-1403A>T, AT vs. AA, HR(adj) = 2.20, 95 % CI 1.11-4.36, p = 0.02), rather than rectal cancer. None of SNPs located at hMSH2 were significantly associated with prognosis of CRC. Our findings suggested that common variants in hMLH1 may serve as a predictor of CRC survival.
authors.affiliation: Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Yibaina
authors.initials: Y
authors.lastname: Wang
authors.forename: Guangxiao
authors.initials: G
authors.lastname: Li
authors.forename: Fulan
authors.initials: F
authors.lastname: Hu
authors.forename: Haoran
authors.initials: H
authors.lastname: Bi
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.forename: Shuying
authors.initials: S
authors.lastname: Li
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.forename: Binbin
authors.initials: B
authors.lastname: Cui
authors.forename: Xinshu
authors.initials: X
authors.lastname: Dong
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein