title: Prognostic significance of hMLH1/hMSH2 gene mutations and hMLH1 promoter methylation in sporadic colorectal cancer.
abstract: No study in China has focused on the relationships between germline and somatic hMLH1/hMSH2 gene mutations, hMLH1 promoter methylation, and the prognosis of colorectal cancer (CRC), especially in sporadic CRC. Therefore, we carried out this study with 433 primary sporadic CRC patients to investigate the associations between germline and somatic hMLH1/hMSH2 gene mutations, hMLH1 promoter methylation, and the overall survival (OS) of CRC; to evaluate the effect of interaction between gene mutation and methylation on the risk of CRC prognosis. As a result, the 3-, 5-, and 7-year survival of the sporadic CRC patients was 67, 57, and 50.0 %, respectively. There were no significant associations observed between germline and somatic hMLH1/hMSH2 gene mutations after adjusted (HR = 1.37, 95 % CI 0.70-2.67, p = 0.35; HR = 1.31, 95 % CI 0.69-2.47, p = 0.42, respectively). When the analyses were stratified based on tumor stage, tumor location, and chemotherapy, no significant survival advantage of hMLH1/hMSH2 gene mutation was illustrated. In addition, no significant association between germline and somatic hMLH1 promoter methylation and OS of CRC was observed (HR = 1.46, 95 % CI 0.57-3.74, p = 0.43; HR = 0.70, 95 % CI 0.32-1.53, p = 0.37, respectively). In conclusion, the research did not find the significant association between germline and somatic hMLH1/hMSH2 gene mutations, hMLH1 promoter methylation, and sporadic CRC prognosis.
authors.affiliation: Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, People's Republic of China.
authors.forename: Yibaina
authors.initials: Y
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Chong
authors.initials: C
authors.lastname: Teng
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Binbin
authors.initials: B
authors.lastname: Cui
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Fulan
authors.initials: F
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein