rs705117

This study examined genetic variants in the vitamin D pathway using GWAS data from 3,686 women of African ancestry (1,657 cases). No significant associations were found between vitamin D pathway variants and breast cancer risk overall or by estrogen receptor status (pathway P > 0.5, SNP-level P adj > 0.2). Mendelian randomization analysis showed no association with genetically predicted 25(OH)D levels (P = 0.23). However, a nonsense variant rs41302073 in TYRP1 (pigment synthesis pathway) showed a 54% increased risk of breast cancer (OR = 1.54, 95% CI = 1.24-1.91, P adj = 0.007), warranting further investigation of non-vitamin D mechanisms.

This study examined 89 genetic sequence variants in six vitamin D metabolism pathway genes (VDR, GC, CYP24A1, CYP27A1, CYP27B1, CYP2R1) in 522 early-stage head and neck cancer patients to assess associations with overall survival and second primary cancer risk. GC rs4588 and CYP2R1 rs10500804 were associated with lower serum vitamin D levels. CYP24A1 rs2296241 (aHR 1.23, p=0.05) was significantly associated with worse overall survival, while CYP2R1 rs1993116 (aHR 0.59, p=0.001) was protective against second primary cancer, independent of serum vitamin D levels.

This family-based association study tested 12 SNPs in the vitamin D-binding protein (DBP) gene for association with compression strength index (CSI), a composite measure of hip fracture risk, in 1,873 Caucasian subjects from 405 nuclear families. Two SNPs showed significant associations with CSI in males: rs222029 (P=0.0019, R²=1.80%) and rs222020 (P=0.0042, R²=1.60%), with the A-A-A haplotype conferring 4.4% higher CSI than the G-G-G haplotype. Findings suggest DBP gene polymorphisms influence CSI phenotype particularly in Caucasian males.