ECTS2013 Poster Presentations Genetics (17 abstracts)
1Medical University of Graz, Graz, Austria; 2GKK Outpatient Department, Graz, Austria; 3Synlab Services LLC, Mannheim, Germany.
Preclinical and epidemiologic data suggest that vitamin D deficiency may play a role in the pathogenesis and progression of prostate cancer. Based on recently reported genetic determinants of vitamin D insufficiency we investigated a functional T>G single nucleotide polymorphism (SNP) in the group-specific component (GC) gene for its association with 25-hydroxy (25-OH) vitamin D and 1.25 dihydroxy (1.25-OH) vitamin D levels and further to test a possible association with metastatic progression and mortality of prostate cancer.
The association of the GC variant with vitamin D levels was analyzed in male participants of the cross-sectional LURIC study comprising 2310 men. The role of the GC variant in prostate cancer outcome was analyzed in the prospective PROCAGENE study comprising 702 prostate cancer patients with a median follow-up of 82 months.
In the LURIC study, the G allele of the GC polymorphism was associated with lower 25-OH-vitamin D levels (TT genotype: 18.6 ng/ml; TG: 17.9 ng/ml; GG: 15.1 ng/ml, P≤0.001) and lower 1.25-OH-vitamin D levels (TT: 36.4 pmol/l; TG: 35.5 pmol/l; GG: 32.7 pmol/l, P=0.004). In the PROCAGENE cohort, GC genotypes were not associated with biochemical recurrence (HR 0.89, 95% CI 0.701.13; P=0.32), development of metastases (HR 1.20, 95% CI 0.881.63; P=0.25) or overall survival (HR 1.10; 95% CI 0.841.43; P=0.50).
We conclude that a causal role of vitamin D SNPs in disease progression and mortality in prostate cancer patients is unlikely.