Loss of heterozygosity of methylenetetrahydrofolate reductase in colon carcinomas

Folate derivatives are essential for DNA synthesis and methylation. A large proportion of the Caucasian population is heterozygous for a common substi tution, 677C --> T (alanine --> valine), in methylenetetrahydrofolate reduc tase (MTHFR), an enzyme of folate interconversion. Homozygous mutant indivi duals, approximately 10-15% of North Americans, have been reported to have a reduced risk of colorectal cancer. We examined lymphocyte and tumor tissu e DNA from colorectal carcinoma patients from two different populations to assess loss of heterozygosity (LOH) of MTHFR. We observed LOH in approximat ely 16% of colorectal tumors; in 8 of the 11 tumors with LOH, the mutant va line allele was lost. Additional studies are required to determine if prefe rential loss of the mutant allele is a common finding that could contribute to colorectal tumorigenesis.