Vitamin D Receptor Cdx-2 Polymorphism and Premenopausal Breast Cancer Risk in Southern Pakistani Patients

Abstract

BackgroundVitamin D3 is a secoster oid that exerts its effect by binding to its nuclear receptor called vitamin D receptor (VDR), inducing apoptosis and thereby inhibiting cell proliferation in cancer cells. The VDR receptor, located in the nucleus, is known to regulate the functions of over 200 genes. Various allelic forms of hVDR have been discovered that increase susceptibility to various cancers. The VDR-Cdx2 polymorphism, located in the promoter region of exon 1e in the VDR gene, influences the functional activity of the receptor, since the hVDR lacks consensus TATA and CAAT boxes. The current investigation examines the association between VDR-Cdx2 polymorphism and breast cancer in premenopausal females from Southern Pakistan.MethodsWe conducted a case control study on 264 subjects (103 cases and 161 controls) who were recruited from a tertiary hospital located in Karachi, Pakistan. Genomic DNA was extracted from peripheral blood using a commercial kit method, and the VDR-Cdx2 polymorphism was genotyped using tetraprimer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method. Pearson chi square test was used to assess the association between VDR-Cdx2 genotype and breast cancer while genotype distribution in controls was evaluated by Hardy-Weinberg equilibrium (HWE). Breast cancer risk was calculated using odds ratios and 95% confidence intervals.ResultsThe genotype distribution in the control group was in HWE (p > 0.05) for the VDR-Cdx2 polymorphism. A non-significant association was observed between VDR cdx2 polymorphism and breast cancer, however the GG genotype was at risk (OR = 1.832, 95% CI = 0.695–4.828) of developing breast cancer.ConclusionThe GG genotype of Cdx2-VDR gene polymorphism may increase the risk of developing breast cancer in young female patients in South Pakistan. Further investigations examining additional single nucleotide polymorphisms (SNPs) in VDR are required to assess their relationships with breast cancer.

A Review of the Epidemiology of Breast Cancer in Asia: Focus on Risk Factors

“…Dietary factors associated with increased BC risk included intake of total n-6 polyunsaturated fatty acids (PUFA) (Kiyabu et al, 2015), vitamin D deficiency or insufficiency (Shi et al, 2014a;Park et al, 2015a), high levels of serum cadmium (Nagata et al, 2013;Itoh et al, 2014;Ding et al, 2015), high intake of salt (Park et al, 2014b), sugar (Sulaiman et al, 2014), meat (Ko et al, 2013), and saturated fat and oils (Balasubramaniam et al, 2013;Wang et al, 2013a). In women with BC, the trace elements, cadmium, magnesium, copper, cobalt and lithium, were found in high levels.…”

Vitamin D Receptor Polymorphism and Cancer: An Update

“…Similarly, various casecontrol studies suggested that the association between VDR polymorphism and risk of breast cancer may depend on race and ethnicity. Furthermore, these studies also showed inconsistent results, some suggesting the association of VDR polymorphism with breast cancer, while others suggested a lack of association (3,19,(24)(25)(26)(27)(28)(29)(30)(31). No association between VDR polymorphisms and breast cancer risk was found, however, modification of this relationship was observed with the menopausal status in Europeans (VDR rs4328262 and rs11168292) and East Asians (VDR rs11168287).…”

Vitamin D, Its Receptor Gene Polymorphism and Breast Cancer

“…VDR gene polymorphism is associated with the breast cancer risk [117][118][119][120][121][122][123][124][125] but insufficient data are available to find the relationship with breast cancer risk [126]. The studies have pointed out allelic variations in VDR gene, such as Cdx2, Fok1, Bsm1, Taq1, Apa1 and Poly A in different ethnic groups with breast cancer incidence with contradictory results [117,118,121,126].…”

“…The studies have pointed out allelic variations in VDR gene, such as Cdx2, Fok1, Bsm1, Taq1, Apa1 and Poly A in different ethnic groups with breast cancer incidence with contradictory results [117,118,121,126].…”

“…Recently, a meta-analysis has documented that Cdx2 polymorphism is linked with breast cancer susceptibility only in Africans [127]. However, no profound relations was observed between Cdx2 polymorphism and breast cancer risk among Pakistani population [126].…”