Am J Epidemiol 2002; 156:885-902.
Copyright © 2002 by Johns
Hopkins Bloomberg School of Public Health
HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW |
Mismatch Repair Genes hMLH1 and hMSH2 and Colorectal Cancer: A HuGE Review
1 Department of Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, United Kingdom.
2 Colon Cancer Genetics Group, MRC Human Genetics Unit, University of Edinburgh and Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
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.
colorectal neoplasms; epidemiology; genetic screening; germ-line mutation; hMLH1; hMSH2; penetrance; survival
Abbreviations: Abbreviations: hMLH1, human mutL homolog 1; hMSH2, human mutS homolog 2; HNPCC, hereditary nonpolyposis colorectal cancer; MSI, microsatellite instability.
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