Apolipoprotein E gene polymorphism and colorectal cancer: gender-specific modulation of risk and prognosis.

Apolipoprotein E ( ApoE ) gene polymorphism is a major factor in lipid metabolism. It has been suggested that this polymorphism can modulate colorectal tumour risk. We tested this hypothesis for colorectal cancer (CRC). ApoE genotype was determined in 206 patients with CRC and 353 healthy controls from the East Anglia region of the U.K. Compared with individuals possessing the most common epsilon 3/epsilon 3 genotype, those with the epsilon 2/epsilon 3 genotype had an increased risk of colon cancer [odds ratio (OR) = 1.91; 95% confidence interval 1.05-3.45]. However, this association was strongly affected by gender. Separate analysis of male and female subjects revealed a highly significant association in men (OR = 2.71; 95% confidence interval 1.30-5.65), but no association in women (OR = 1.01; 95% confidence interval 0.37-2.77). Likewise, the proportion of male patients with more advanced tumours (Dukes' C&D) was significantly increased among those with the ApoE epsilon 2/epsilon 3 genotype (OR = 4.16; 95% confidence interval 1.36-12.75). No significant effect of the presence of the epsilon 4 allele on CRC risk was found; however, there were no epsilon 4/epsilon 4 homozygotes among patients with proximal colon cancers. The ApoE epsilon 3/epsilon 3 majority genotype appeared to be associated with the lowest risk of CRC. These results suggest that ApoE genotype can influence both CRC risk and prognosis of the existing disease in a gender-dependent manner.