Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: A HuGE review

R. J. Mitchell, S. M. Farrington, M. G. Dunlop, H. Campbell*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract / Description of output

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 languageEnglish
Pages (from-to)885-902
Number of pages18
JournalAmerican Journal of Epidemiology
Issue number10
Publication statusPublished - 15 Nov 2002

Keywords / Materials (for Non-textual outputs)

  • Colorectal neoplasms
  • Epidemiology
  • Genetic screening
  • Germ-line mutation
  • hMLH1
  • hMSH2
  • Penetrance
  • Survival


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