Abstract
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.
Original language | English |
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Pages (from-to) | 885-902 |
Number of pages | 18 |
Journal | American Journal of Epidemiology |
Volume | 156 |
Issue number | 10 |
DOIs | |
Publication status | Published - 15 Nov 2002 |
Keywords / Materials (for Non-textual outputs)
- Colorectal neoplasms
- Epidemiology
- Genetic screening
- Germ-line mutation
- hMLH1
- hMSH2
- Penetrance
- Survival