Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review.
Evidence to support a role for the mismatch repair genes human mutL homolog 1 (hMLH1) and human mutS homolog 2 (hMSH2) in the etiology of colorectal cancer has come from linkage analysis, segregation studies, and molecular biologic analysis. More recently, carriers of potentially pathogenic mutations in the hMLH1/hMSH2 genes have consistently been shown to be at a greatly increased risk of developing colorectal cancer compared with the general population. When considered together, the available evidence shows a strong, consistent, and biologically plausible association between mismatch repair gene mutations and colorectal cancer. The penetrance of mutations in hMLH1/hMSH2 is incomplete and is significantly higher in males (approximately 80%) than in females (approximately 40%). To date, evidence for gene-gene or gene-environment interactions is limited, although preliminary studies have revealed a number of avenues that merit exploration. Population screening for mutation carriers is not currently a feasible option, and mutation analysis remains restricted to either relatives of mutation carriers or colorectal cancer cases selected on the basis of phenotype.
Mitchell
R J
RJ
Department of Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, United Kingdom.
Farrington
S M
SM
Dunlop
M G
MG
Campbell
H
H
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch / Q000235:genetics*; D002352:Carrier Proteins; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D005820:Genetic Testing / Q000379:methods / Q000592:standards; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008967:Molecular Biology; D000070957:MutL Protein Homolog 1; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D019683:Penetrance; D010641:Phenotype; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012737:Sex Factors
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1