Abstract
BackgroundVitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). Although African-Americans have the lowest levels of serum vitamin D, there is a dearth of information on VDR gene polymorphisms and breast cancer among African-Americans and Hispanics. This study examines whether VDR gene polymorphisms are associated with breast cancer in these cohorts.MethodsBlood was collected from 232 breast cancer patients (Cases) and 349 non-cancer subjects (Controls). Genotyping for four polymorphic variants of VDR (FokI, BsmI, TaqI and ApaI) was performed using the PCR-RFLP method.ResultsAn increased association of the VDR-Fok1 f allele with breast cancer was observed in African-Americans (OR = 1.9, p = 0.07). Furthermore, the FbTA, FbtA and fbtA haplotypes were associated with breast cancer among African-Americans (p<0.05). Latinas were more likely to have the VDR-ApaI alleles (Aa or aa) (p = 0.008). The VDR-ApaI aa genotype was significantly associated with poorly-differentiated breast tumors (p = 0.04) in combined Cases. Kaplan-Meier survival analysis showed decreased 5-year disease-free-survival (DFS) in breast cancer patients who had the VDR-Fok1 FF genotype (p<0.05). The Cox regression with multivariate analysis revealed the independent predictor value of the VDR-FokI polymorphism for DFS. The other three variants of VDR (BsmI, TaqI and ApaI) were not associated with disease outcome.ConclusionsVDR haplotypes are associated with breast cancer in African-Americans, but not in Hispanic/Latinas. The VDR-FokI FF genotype is linked with poor prognosis in African-American women with breast cancer.
Highlights
Several studies have demonstrated a decrease in Vitamin D receptor (VDR) expression in breast cancer cells compared to normal breast cells [1]
Decreased levels of VDR in breast cancer cells could be due to VDR gene polymorphisms [2], and/or DNA methylation [3–5]
The VDR gene polymorphisms were genotyped in 188 AfricanAmerican and 393 Hispanics/Latina women
Summary
Several studies have demonstrated a decrease in Vitamin D receptor (VDR) expression in breast cancer cells compared to normal breast cells [1]. Alterations in VDR expression and activity could lead to deregulation of Vitamin D uptake, metabolism, and serum levels of biologically active Vitamin D. VDR gene has multiple gene polymorphisms [6], and four important single nucleotide polymorphisms (SNPs) in exon 2 and 39UTR region. These are VDR-FokI (rs2228570), VDR-BsmI (rs1544410), VDR-TaqI (rs731236) and VDR-ApaI (rs7975232). Large meta-analyses have demonstrated a significant association of the VDR FokI polymorphisms with breast cancer [9,10], and other cancers across multiple ethnic cohorts [11,12]. African-Americans have the lowest levels of serum vitamin D, there is a dearth of information on VDR gene polymorphisms and breast cancer among African-Americans and Hispanics. This study examines whether VDR gene polymorphisms are associated with breast cancer in these cohorts
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