Vitamin D Receptor Gene Polymorphisms and Prognosis of Breast Cancer among African-American and Hispanic Women

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.

Association Between VDR Polymorphisms and Breast Cancer: An Updated and Comparative Meta-analysis of Crude and Adjusted Odd Ratios

“…Case-control studies on Fok1 in breast cancer showed some evidence of increased risk among ff carriers (Sinotte et al, 2008;Gapska et al, 2009;McKay et al, 2009), which was confirmed by some later metaanalysis Tang et al, 2009;. However, these studies also reported some decreased risk among ff carriers (Anderson et al, 2011), or no association with breast cancer (Curran et al, 1999;Guy et al, 2004;John et al, 2007;Abbas et al, 2008;Engel et al, 2012;Rollison et al, 2012;Fuhrman et al, 2013;Mishra et al, 2013;Shahbazi et al, 2013). Similarly, mixed results have been observed concerning the relationship between other polymorphisms and the risk of breast cancer development.…”

Do VDR Gene Polymorphisms Contribute to Breast Cancer?

“…The important and intensively studied single nucleotide polymorphisms (SNPs) of VDR are, FokI (rs2228570), VDR-BsmI (rs1544410), VDR-TaqI (rs731236), VDRApaI (rs7975232) and Poly(A) (Alimirah et al, 2011). Over the years, most of The molecular epidemiological studies have been done to relate the associations of important VDR polymorphisms with breast cancer (Curran et al, 1999;Ingles et al, 2000;Bretherton et al, 2001;Hou et al, 2002;Buyru et al, 2003;Guy et al, 2004;Sillanpaa et al, 2004;Chen et al, 2005;Lowe et al, 2005;John et al, 2007;Mc Cullough et al, 2007;Trabert et al, 2007;Abbas et al, 2008;Barroso et al, 2008;Sinotte et al, 2008;Chakraborty et al, 2009;McKay et al, 2009;Rollison et al, 2011;Huang et al, 2012;Mishra et al, 2013;Du et al, 2014 Ethnic Variation in VDR Gene Polymorphisms: VDR gene show sequence level dissimilarity in the different populations, both at the 5' and 3' termini (Trabert et al, 2007). Epidemiological studies have frequently reported that the fundamental features of the population with varying ethnicities can alter the links between VDR gene polymorphisms and carcinoma.…”

“…Individuals are categorized as having alleles with short (S, with <18 As) or long (L, with >18 As) poly (A) stretches. The S allele is considered to be the more effective VDR allele (Mishra et al, 2013).…”

“…Fouzia Shaikh*, Saeeda Baig, Qamar Jamal with advanced stages of breast cancer with large lesions, and are prone to develop metastasis with bad prognosis (Bhurgri et al, 2006;Naveed et al, 2014). In the UK between the years 2009 and 2011, approximately 80% of breast cancer cases were diagnosed above the age of 50 years, and about 24% in women aged 75 years and above, based on Breast cancer incidence statistics (2013).…”

Lack of association of vitamin D receptor gene polymorphisms/haplotypes in Sjögren’s syndrome

“…Three polymorphisms, BsmI and ApaI (both in intron 8), and TaqI (in exon 9) have been identified at the 3' end of the gene. Recent studies have reported that allelic variations of the VDR gene polymorphisms might be associated with a variety of diseases, including osteoarthritis, diabetes, cancer, cardiovascular diseases, tuberculosis, virus infections, urinary stones, periodontitis [13][14][15][16][17][18]. These findings suggest that allelic variations of the VDR gene may partially represent a genetic component associated with the development of autoimmune diseases.…”