ABSTRACT
BACKGROUND:
The relationship between
vitamin D and
prostate cancer has primarily been characterized among
White men. However, Black
men have higher
prostate cancer incidence and
mortality rates, chronically low circulating
vitamin D levels, and ancestry-specific genetic variants in
vitamin D-related
genes. Here, we examine six critical
genes in the
vitamin D pathway and
prostate cancer risk in Black
men.
METHODS:
We assessed a total of 69 candidate variants in six
genes ( GC, CYP27A1,
CYP27B1,
CYP24A1, VDR , and RXRA ) including functional variants previously associated with
prostate cancer and circulating 25(OHD) in
White men.
Associations with
prostate cancer risk were examined using
genome-wide association study data for approximately 10,000
prostate cancer cases and 10,000 controls among Black
men and over 85,000 cases and 91,000 controls among
White men. A statistical significance threshold of 0.000724 was used to account for the 69 variants tested.
RESULTS:
None of the variants examined were significantly associated with
prostate cancer risk among Black
men after multiple comparison
adjustment. Four variants tested P<0.05 in Black
men, including two in RXRA (rs41400444 OR=1.09, 95% CI 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.87-1.00, P = 0.046) and two in VDR (rs2853563 OR = 1.07, 1.01-1.13, P = 0.017 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.045). Two variants in VDR were also positively associated with
risk in
White men (rs11568820 OR = 1.04, 1.02-1.06, P = 0.00024 and rs4516035 OR = 1.03, 1.01-1.04, P = 0.00055).
CONCLUSION:
We observed suggestive non-significant
associations between genetic variants in RXRA and VDR and
prostate cancer risk in Black
men.
Future research exploring the relationship of
vitamin D with
cancer risk in Black
men will need larger
sample sizes to identify ancestry-specific variants relevant to
risk in this
population.