Genetic association of vitamin D receptor variants and 25-hydroxyvitamin D levels with breast cancer risk and triple-negative phenotype in Bangladesh

Breast cancer is increasing in Bangladesh with high rate of aggressive subtypes such as Triple-Negative Breast Cancer (TNBC). But population-specific genetic evidence remains limited. This study evaluated the association of Vitamin D Receptor ( VDR ) polymorphisms and serum 25-hydroxyvitamin D [25(OH)D] levels with breast cancer risk among Bangladeshi women. This case-control study was conducted involving 300 breast cancer patients and 204 healthy controls. Serum 25(OH)D concentrations were measured using high-performance liquid chromatography (HPLC) and VDR polymorphisms ( FokI , BsmI , ApaI , and TaqI ) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Associations were assessed using multimodal logistic regression and receiver operating characteristic (ROC) curve analyses. Breast cancer patients exhibited significantly lower serum 25(OH)D levels than controls ( p = 0.002). Under a recessive inheritance model, the FokI C/C genotype found to be a major risk factor for breast cancer (OR = 3.53, p < 0.001). Subtype-stratified analysis revealed notable enrichment of the TaqI T/T genotype among TNBC patients ( p = 0.007). An integrated clinicogenetic model combining FokI C/C, TaqI T/T, and BsmI G/G genotypes with age, body mass index (BMI), and menopausal status demonstrated strong discriminatory performance (AUC = 0.776). The model outperforms a genotype-only model (AUC = 0.670; p < 0.001). These findings indicate that FokI C/C and TaqI T/T polymorphisms are important genetic markers of breast cancer susceptibility in Bangladeshi women. The TaqI T/T showed subtype-specific enrichment in TNBC. The observed association between vitamin D deficiency and breast cancer risk highlights the potential contribution of vitamin D signaling pathways to disease development. The proposed clinicogenetic model may support early risk stratification and personalized screening approaches, although validation in independent South Asian populations is required.