Association of VDR ApaI and TaqI Polymorphisms with Breast Cancer Risk in Libyan Women

Abstract

Vitamin D receptor (VDR) gene polymorphisms, particularly ApaI (rs7975232) and TaqI (rs731236), have been inconsistently associated with breast cancer (BC) risk across diverse populations. No data exist on their role in Libyan women. The objective of this study was to investigate the association between VDR ApaI and TaqI polymorphisms and BC susceptibility in a Libyan case-control cohort. Methods: This study included 56 histologically confirmed BC patients and 58 healthy controls. Genotyping was performed using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP), validated by Sanger sequencing. Genetic association was tested under multiple inheritance models (codominant, dominant, recessive, over-dominant, log-additive). Linkage disequilibrium (LD) and haplotype analyses were conducted. Results: No statistically significant association was found for either polymorphism. Analysis of the ApaI polymorphism revealed a non-significant, protective trend for the homozygous variant (a/a) genotype (OR = 0.48, 95% CI: 0.15–1.54, P = 0.45, codominant model). Conversely, a non-significant trend toward higher risk was observed for the TaqI homozygous variant (t/t) genotype (OR = 2.40, 95% CI: 0.73–7.86, P = 0.28, codominant model). For both markers, the observed genotype distributions did not deviate significantly from Hardy-Weinberg equilibrium (P > 0.05). A significant moderate linkage disequilibrium was observed between the two SNPs (D’ = 0.7786, P = 0). Haplotype analysis revealed no significant association with BC risk. Conclusion: This first genetic association study of VDR ApaI and TaqI in Libyan women does not support a major role for these specific polymorphisms in BC etiology. The findings provide crucial baseline genetic data for North Africa and underscore the importance of population-specific studies to clarify the heterogeneous global patterns of association of VDR variants.