Association of apolipoprotein e polymorphisms and dietary factors in colorectal cancer

Abstract

ApoE single nucleotide polymorphisms (SNPs) Cys112Arg (Epsilon-4), and Arg158Cys (Epsilon-2) have been implicated in cardiovascular and Alzheimer's disease, but their role in colorectal cancer (CRC) has not been extensively studied. We investigated whether ApoE polymorphisms alone or in combination with dietary factors selectively contribute to mismatch-repair (MMR) proficient (microsatellite stablelow or MSSL) vs deficient (microsatellite unstable or MSI-H) CRCs. We carried out a case-control study with 906 CRC cases and 911 unaffected controls to examine the associations between ApoE polymorphisms and dietary factors and assessed their contribution to MSSL and MSI-H CRCs. We used unconditional logistic regression to evaluate the associations between ApoE SNPs, tumour MSI status, and dietary factors after adjusting for age and sex. All statistical tests were two-sided. No significant differences in ApoE genotype frequencies were observed between CRC cases and unaffected controls. We observed that increased dietary intake of total fat, saturated fat, cholesterol, and red meat was significantly associated with CRC. Among non-ApoE4 carriers, 2-4 and >4 red meat servingsweek were associated with developing MSSL CRC (OR1.51, 95 CI 1.10-2.07 and OR1.80, 95 CI 1.30-2.48, respectively), whereas among ApoE4 allele carriers, four or more red meat servingsweek were associated with MSI-H CRC (OR4.62, 95 CI 1.20-17.77) when compared with the controls. ApoE isoforms modulate the risk of MSI-H and MSSL CRCs among high red meat consumers. © 2009 Cancer Research UK.