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 stable/low or MSS/L) 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 MSS/L 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 twosided. 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 44 red meat servings/week were associated with developing MSS/L CRC (OR ¼ 1.51, 95% CI 1.10 -2.07 and OR ¼ 1.80, 95% CI 1.30 -2.48, respectively), whereas among ApoE4 allele carriers, four or more red meat servings/ week were associated with MSI-H CRC (OR ¼ 4.62, 95% CI 1.20 -17.77) when compared with the controls. ApoE isoforms modulate the risk of MSI-H and MSS/L CRCs among high red meat consumers.

Amino Acids Activate Mammalian Target of Rapamycin Complex 2 (mTORC2) via PI3K/Akt Signaling

“…At the organismal level, deregulation of mTOR complex activity has been linked to aging and to diseases like diabetes or cancer (11,(23)(24)(25)(26). Furthermore, mTOR inhibitors have been used to extend lifespan in mice and in clinical treatments of several human cancers, including mantle cell lymphoma, endometrial cancer, and renal cell carcinoma (26,73,74).…”

“…A number of studies point to the importance of nutrients in the etiology of some major diseases, such as insulin-resistant obesity (23) or cancer (24,25) and in the aging process (11,26). In humans, circulating amino acid levels are elevated in obese individuals, and this is related to an increase in insulin resistance (23,27,28).…”

A Case-Control Study on the Effect of Apoliprotein E Genotype on Head and Neck Cancer Risk

“…The effect of apoE genotypes has been investigated in relation to breast, colorectal, biliary tract, prostate cancer and hematologic malignancies (7,(16)(17)(18)35), with conflicting results. Trompet et al (19) recently addressed the relationship between cholesterol and cancer by studying both the effect of plasma cholesterol levels and apoE isoforms on overall cancer risk during a 3-year follow-up study in a large elderly cohort (19).…”

“…This approach has been called "Mendelian randomization" (14,15), and it has been recently adopted to evaluate the association between cholesterol levels and cancer risk by using the apoE genotype as a surrogate for cholesterol levels. Results, however, are largely conflicting (7,(16)(17)(18). Trompet et al (19) recently reported the results of a large cohort study measuring the apoE genotype, plasma cholesterol levels, and overall cancer incidence and mortality during a 3-year follow-up period.…”

“…As for the AD, the ε4 allele is among the few established risk factors because of its higher in vitro binding of amyloid β peptides compared with the ε3 allele (6). About CHD, the ε2 allele is associated with a 20% decreased risk, probably resulting from an advantageous lipid profile due to a high efficient binding of apoE ε2 isoform with small, phosholipid-enriched high-density lipoprotein (HDL) (7).…”