Apolipoprotein E genetic polymorphism, serum lipoproteins, and breast cancer risk

Abstract

Apolipoprotein E (apoE) is a polymorphic gene involved in lipid metabolism with three common variant alleles (epsilon2, epsilon3, and epsilon4). The epsilon4 allele has been associated with elevated levels of cholesterol as well as greater risk of coronary heart disease and Alzheimer's disease. In this case-control study we examined whether apoE genotype affected the association between serum lipids and breast cancer risk. In a subset of a study in western New York, 260 women with incident, primary breast cancer and 332 community controls were interviewed and provided blood samples. Polymerase chain reaction-restriction fragment length polymorphism analyses of the apoE polymorphism were performed. Participants were classified as apoE2 (epsilon2, epsilon2 or epsilon2, epsilon3), apoE3 (epsilon3, epsilon3), or apoE4 (epsilon4, epsilon4 or epsilon4, epsilon3). No unconditional logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with the apoE3 genotype, there were no associations with risk for women with the apoE2 (OR=1.0; 95% CI=0. 91-1.64) or apoE4 genotype (OR=0.97; 95% CI=0.63-1.54). Higher serum levels of total cholesterol, HDL cholesterol, and LDL cholesterol were not associated with risk, either in the total sample or among subgroups of women defined by apoE genotype. Women with the highest serum triglyceride levels had an increase in risk (OR=1.63; 95% CI=1. 03-2.59) compared to women with the lowest levels. This effect was not apparent among women with the apoE2 or apoE3 genotype, but much stronger among women with the apoE4 genotype (OR=4.69; 95% CI=1. 49-14.7). These data suggest that the apoE4 genotype may modify the association between serum triglycerides and breast cancer risk.

A Comparitive Study to Evaluate the Role of Serum Lipid Levels in Aetiology of Carcinoma Breast

“…Studies have shown that obese women are more likely to have large tumors, greater lymph node involvement, and poorer breast cancer prognosis with 30% higher risk of mortality [5]. Levels of circulating lipids and lipoproteins have also been associated with high breast cancer risk, though published results have been varying [6][7][8].…”

Influences of apolipoprotein E polymorphism on the risk for breast cancer and HER2/neu status in Taiwan

“…Among Caucasian American women possessing one or two copies of APOE4 allele, those with high concentrations of triglycerides had four times the risk of developing breast cancer when compared with women with low triglyceride concentrations [11]. However, compared with women in possession of the APOE3 allele, there were no associations with breast cancer risk for Caucasian [12] or English [13] women with either the APOE2 or APOE4 alleles. Taken together, the impact of APOE polymorphism on breast cancer risk may vary across diverse populations.…”

Association of NQO1 polymorphism with spontaneous breast cancer in two independent populations

“…BRCA1 and BRCA2 are the well-established susceptibility genes for familial breast cancer (Dunning et al, 1997(Dunning et al, , 2001Healey et al, 2000;Nathanson and Weber, 2001;Goode et al, 2002), TP53 is a gene involved in apoptosis (Dumont et al, 2003), ApoE influences lipid metabolism and cardiovascular disease (Menzel et al, 1983) and may be involved in tumour proliferation (Moysich et al, 2000;Zunarelli et al, 2000), NQO1 is engaged in carcinogen metabolism (Nebert et al, 2002) and GNB3 is part of a signal transduction pathway (Siffert et al, 1998).…”

“…The 72P allele of the polymorphism in TP53 was only weakly associated with an increased risk for breast cancer (Nathanson and Weber, 2001). No association of breast cancer was observed with the apolipoprotein E polymorphism (Moysich et al, 2000;Zunarelli et al, 2000). For the P187S polymorphism in NQO1, conflicting results were published (Siegelmann-Danieli and Buetow, 2002;Hamajima et al, 2002).…”