Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals

Abstract

We evaluated genetic variants of apolipoprotein E (APOE HhaI) and their association with serum lipids in colorectal cancer (CRC), together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412) and APOE*4 (rs429358) were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the ε4/ε4 genotype (6%) was present only in controls. The patients had reduced levels (mean ± SD) of total cholesterol and low-density lipoprotein cholesterol fraction (180.4 ± 49.5 and 116.1 ± 43.1 mg/dL, respectively) compared to controls (204.2 ± 55.6, P = 0.135 and 134.7 ± 50.8 mg/dL; P = 0.330, respectively) indicating that they were not statistically significant after the Bonferroni correction. The APOE*4 allele was associated with lower levels of total cholesterol, low-and high-density lipoprotein cholesterol fraction and increased levels of very low-density lipoprotein cholesterol fraction and triglycerides only among patients (P = 0.014). There was a positive correlation between the altered lipid profile and increased body mass indexes in both groups (P < 0.010). Moreover, a higher rate of hypertension and overweight was observed in controls (P < 0.002). In conclusion, the presence of the ε4/ε4 genotype only in controls may be due to a protective effect against CRC. Lower lipid profile values among patients, even those on lipid-rich diets associated with the APOE*4 allele, suggest alterations in the lipid synthesis and metabolism pathways in CRC.

Apolipoprotein E Polymorphism and Colorectal Neoplasm: Results from a Meta-Analysis

“…Five studies of the ε2 vs. ε3 alleles were enrolled in this analysis [6], [24], [25], [34], [35], [37]. The combined results based on these 6 studies showed that, compared with those with ε2 alleles, there was no significant risk of CRC of individuals with the ε3 alleles (OR 1.03, 95% CI 0.92 to 1.16, p = 0.60, Figure 3, A).…”

“…Of these, 10 records were excluded because they did not match the detailed criteria. At last, we identified 8 eligible studies, published from 1996 to 2009, that reported on polymorphisms of APOE and risk of CRN [6], [24], [25], [26], [34], [35], [36], [37]. Studies were carried out in Japan, Brazil, China, Australia, Finland, USA, UK and Canada.…”

“…Appropriate genotyping methods for APOE were stated in all studies, all of which was polymerase chain reaction restriction fragment length polymorphism except 1 study [35] using immunoblotting techniques. The deviation from Hardy–Weinberg equilibrium was assessed by the HWE program, and the results indicated that the genotype distribution of control population in most of the eight included studies were in Hardy–Weinberg equilibrium except one study [25].…”

“…All 8 studies were eligible for assessing the impact of at least one of APOE alleles on the CRN risk [6], [24], [25], [26], [34], [35], [36], [37]. Comparison of prevalence of the ε2 vs. ε3 alleles among cases and controls showed no statistically significant heterogeneity between studies (Q = 6.03, p = 0.54, I 2  = 0%, Figure 2A).…”

“…A study reported that APOE E4 may be a protective factor for CRC while those with the E2 or E3 genotype had an increased risk of colon carcinoma in male [24]. In addition, a study from Brazil found the ε4 genotype only presents in controls [25]. A study from China found subjects with APOE ε3/ε4 genotype have lower risk suffering from CRA than those with other genotypes [26].…”