A molecular variant of the APC gene at codon 1822: Its association with diet, lifestyle, and risk of colon cancer

The adenomatous polyposis coli (APC) gene is important in the etiology of c olon cancer. Although germ-line mutations of this gene rarely occur in the population, less penetrant variants of the gene have been reported. One var iant, producing an aspartate to valine change at codon 1822 (B1822V) has be en previously reported as having an allele frequency of 10%, The purpose of this study was to determine whether this B1822V variant of the APC gene is associated with felon cancer and whether its association is influenced by other genetic or environmental factors. We used data collected as part of a multicenter study of 1585 incident cases of colon cancer and 1945 age- and sex-matched population-based controls to evaluate genetic, dietary, and en vironmental associations with the B1822V variant of the APC gene. The frequ ency of the valine/valine allele at codon 1822 was 22.8% in this population . In the control population, 61.5% were homozygote wild type, 33.3% were he terozygotes, and 5.2% were homozygote variant. Cases were slightly less lik ely to have the homozygous variant APC genotype than were controls [odds ra tio (OR), 0.8; 95% confidence interval (CI), 0.6-1.1]; for those diagnosed after age 65, the homozygous APC variant was associated with reduced risk o f colon cancer (OR, 0.6; 95% CI, 0.4-1.0). Assessment of the homozygous APC variant with dietary, genetic, and environmental factors showed that indiv iduals with this genotype were at lower risk if they consumed a low-rat die t (OR, 0.2; 95% CI, 0.1-05) relative to those who were homozygous wild type and ate a high-fat diet. This finding was specific to a low-fat diet and w as unrelated to other dietary variables. These results suggest that the cod on 1822 variant of the APC gene may have functional significance. Individua ls who have the valine/valine variant of this gene may be at reduced risk o f colon cancer if they eat a low-fat diet.