Objective: This study evaluates whether vitamin D receptor (VDR) gene variations are associated with premenopausal breast cancer in Pakistani cohorts.
Methods: Genomic DNA was isolated from 228 breast cancer patients and 500 non-cancer controls. Six polymorphic variants (rs11568820, rs4516035, rs2228570, rs1544410, rs7975232, rs731236) of the VDR gene were genotyped using PCR-RFLP analysis. All statistical analysis was carried out on IBM-SPSS 23 at p-value <.05. Chi-square test and odds ratios (ORs) along with 95% confidence interval (CIs) were applied to evaluate the relationship between VDR gene polymorphisms and breast cancer.
Results: Results showed that the A/A genotype of EcoRV (OR = 2.125, 95% CI = 1.024 to 4.412) and the A/a genotype of Apa1 (OR = 6.094, 95%CI = 4.111 to 9.033) gene polymorphism had an increased risk of premenopausal breast cancer. No associations of the Bsm1 and Taq1 polymorphisms were observed in premenopausal women. Moreover, the Cdx2 GG (OR = 0.34, 95%CI = 0.192-0.602) genotype had a significant protective effect on breast cancer. However, strong LD was existed between Bsm1/Taq1 (D' = 0.757, CI = 0.67-0.82) and Apa1/Taq1 (D' = 0.695, CI = 0.6-0.77). Haplotype analysis showed no association between premenopausal breast cancer and VDR haplotypes.
Conclusion: These analyses indicates that the VDR EcoRV A/A and Apa1 A/a genotypes may be risk factors for breast cancer development among premenopausal women.
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