Apolipoprotein E and the Risk of Breast Cancer in African-American and Non-Hispanic White Women

Abstract

The apolipoprotein genetic polymorphism (APO E) is part of a broader paradigm, highlighting the role of gene-environment interactions as risk factors for human diseases such as cardiovascular disease, Alzheimer’s disease, dementia, atherosclerosis, multiple sclerosis, peripheral artery disease, diabetes, stroke, and most recently, cancer. APO E, a normal constituent of very-low-density lipoproteins and high-density lipoproteins, is involved in many functions, including lipid metabolism, cholesterol transport, tissue repair, immune response and regulation, as well as cell growth and differentiation. The location, frequency and functional effects of this gene have been reviewed elsewhere in terms of cardiovascular disease, Alzheimer’s disease, neuromuscular disease, multiple sclerosis, stroke and diabetes. However, while the majority of studies have examined the significance of APO E as a molecular marker for a variety of diseases in multiethnic populations, few evaluate its role as a putative marker of cancer susceptibility. Fewer explore the importance of APO E on the risk of breast cancer, although some report an association. None have been designed to study its relevance as a marker of breast cancer risk in multiethnic populations. The purpose of this review was to evaluate the association between APO E and the risk for breast cancer in non-Hispanic white and African-American women.

ApoE genotype affects allele-specific apo[a] levels for large apo[a] sizes in African Americans: the Harlem-Basset Study

“…As the apo E4 genotype has been associated with cardiovascular disease, a potential source of error might be a differing distribution of apoE genotypes in this group compared with the population at large. Arguing against this possibility, the apoE allele frequency pattern was similar to that described previously for African American and Caucasian populations (22,23). Furthermore, the apo e4 allele frequency was similar in subjects with and without coronary artery disease for both African Americans (46.7% vs. 53.3%; NS) and Caucasians (51.3% vs. 48.7%; NS).…”

“…This study was undertaken to address a possible impact of apoE genotypes on allele-specific apo[a] levels. Previous studies have shown the following: 1) apoE genotypes have a wide impact on plasma lipoprotein levels (21, 38); 2) apoE allele frequency differs between African Americans and Caucasians (22,23,38); 3) plasma Lp[a] levels differ between African Americans and Caucasians (10-14); and 4) the difference in allele-specific apo[a] levels for larger apo [a] size between African Americans and Caucasians is unexplained (17). In our population, we have shown that African Americans have higher allele-specific apo[a] levels compared with Caucasians.…”

“…Furthermore, as described above, we and others have identified several genetic variations that affect allele-specific apo[a] levels (8,16,17,20). Genetic variability of apolipoprotein E (apoE) is a major determinant of plasma lipoprotein levels (21), and furthermore, apoE genotype frequencies differ between African Americans and Caucasians (22,23). As the African AmericanCaucasian differences in allele-specific apo[a] levels for large apo[a] sizes remain unexplained, we focused on apoE as a possible genetic factor potentially contributing to this difference.…”

Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors*

“…The importance of apoE in atherosclerosis has been attributed in part to its best-defined role as the key determinant for receptormediated uptake and catabolism of triglyceride-rich lipoproteins (VLDL and chylomicrons) and their remnants (1). ApoE also has functions that impact diverse disease processes, including Alzheimerʼs disease and other neuropathologies (2), renal disease (3), cancer (4), and infection. Numerous studies have shown that apoE is involved in immunoregulation and host defense (reviewed in Ref.…”

Ambiguity of Plasma Cholesterol Levels as a Biomarker of Prostate Cancer

“…The relative risk for cancer is believed to be highest in the lowest tertile of serum cholesterol and lowest in the highest. Specifically, cancer mortality rates are said to increase at serum cholesterol levels below 160 mg/dl [6]. A more detailed investigation of the trend in cholesterol levels across disease phases has been provided by studies in breast cancer.…”