UV exposure, vitamin D, and prostate cancer risk in African Americans

Genetics and epidemiological studies have shown that genes and environment interaction play strong roles in prostate cancer (PCa) etiology. PCa incidence and mortality are disproportionately high among African-American (AA) men.;In order to explore the effects of UV exposure, serum Vitamin D, skin color, and vitamin D receptor (VDR) polymorphisms on PCa risk in African-American men; ninety-one affected African-American men with histologically diagnosed adenocarcinoma of the prostate, PSA of > 2.5 ng/ml and a positive digital rectal exam were recruited. Ninety one ethnicity matched controls were also recruited. The mean age of cases and controls was 64.53 and 58.7 years respectively. The mean of serum vitamin D level was 29 ng/ml and 26.75 ng/ml in control and PCa patients respectively. Using the independent samples t-test and Mann-Whitney test there was no significance difference in mean and median of vitamin D serum levels between PCa patients and controls (P=0.42). Interestingly, the mean of tanning potential (relative difference between facultative and constitutive skin pigmentation) was 36.51% and 30.32% among control and PCa subjects, respectively, and, there was moderate association between tanning potential and decreased risk of prostate cancer (OR=0.707, P=0.0626). There was an association between total UV exposure, outdoor UV exposure, recreational UV exposure, and decreased risk of PCa in age matched samples. However the association of decreased prostate cancer risk with total UV exposure and outdoor UV exposure was not significant. These results indicated that when subjects aged 0-5 and 6-11 years old were highly exposed to ultraviolet radiation (UVR), this had significant association with reduced risk of PCa. Moderate UV exposure in all age groups had inverse association with the PCa risk while higher exposure to UVR in advanced age did not protect against PCa. Lower skin pigmentation (higher tanning potential) was associated significantly with reduced risk of PCa. The findings showed that the risk of PCa did not vary significantly by serum concentration of 25(OH)D. Seven polymorphisms in VDR sequence were identified after sequencing. Single nucleotide polymorphisms (SNPs) c.278-69G>A, c.1025-49G>T (ApaI), and c.1025-56A>G were associated with an increasing risk of prostate cancer (OR=1.285, OR=1.22, and OR=2.616 respectively), although these associations were not statistically significant, P>0.05. The less likelihood of prostate cancer risk were found in subjects with SNP c.755+25G>A (OR, 0.256; 95% CI, 0.090-0.729), c.907+75C>T (OR, 0.175; 95% CI, 0.093-0.331), c.1025-95G>A (OR, 0.038; 95% CI, 0.005-0.286), and c.1056T>C (TaqI) (OR, 0.652; 95% CI, 0.338-1.257). These associations were significant although only c.1056T>C was not significant, p=0.201. Collectively, it is possible that genetic variants may mediate PCa risk via a mechanism involving availability of 1, 25(OH)2 D. Vitamin D protects against risk of PCa. UV exposure, adequate vitamin D uptake, and lighter skin along with advantageous VDR polymorphism as modulators of vitamin D can improve this protection. Our results require further corroboration in large statistically powerful sample collections.