The Association Between the Genetic VDR SNP c.907+75C>T and Prostate Cancer Risk Is Modified by Tanning Potential

Abstract

Background: Prostate cancer (PCa) is a multifactorial disease involving complex interactions between genetic and physiological/environmental factors. Vitamin D receptor (VDR) plays a role in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to PCa. Materials and Methods: Logistic regression analysis was used to assess the association of six VDR single nucleotide polymorphisms (SNPs) and factors such as tanning potential and UV sunlight exposure with PCa risk. Results: Marginal significant interactions were found, with a 2-fold increase risk of PCa between SNP 1 (c.278-69G>A) and sunlight UV exposure [odds ratio (OR)=2.02, 95% confidence intervaI (CI)=1.036-4.36; p=0.05]; and a 4-fold increase risk of PCa between SNP 4 (c.907+75C>T) and tanning potential (OR=4.40, 95% CI=0.89-29.12; p=0.0591). In contrast, SNP 5 (rs731236, TaqI) and tanning potential interaction had a protective effect by reducing the risk of PCa by 55% (β=−0.804; OR=0.448, 95% CI=0.197-9.42; p=0.0427). SNPs 2 (rs61614328) and 6 (rs533037428) did not show any association with PCa even in the presence of UV sunlight exposure. Conclusion: The protective effect of SNP 4 from PCa is lost and modified by tanning potential in African Americans. This finding needs to be verified by larger studies in different ethnic populations. Prostate cancer (PCa) has high incidence as well as high mortality, which makes it an important worldwide health issue (1, 2). Furthermore, PCa etiology is complex, involving many risk factors such as age, vitamin D status, ethnic origin, and family history of PCa (3, 4). Epidemiological studies suggest that PCa risk may at least partly be determined by interactions between the environment and genetic predisposition (5-7). PCa rates are higher in African American men compared to other ethnic groups in the United States (4, 5, 8). Additionally, this group of men are more likely to be diagnosed at a later stage of disease development. PCa risk has been inversely associated with sun exposure. In most individuals, about 90% of circulating levels of 25hydroxyvitamin D are derived from casual sun exposure (9). In the United States, high residential sun exposure has been associated with lower mortality rates and reduced risk for PCa (10, 11). A case-control study by Luscombe et al. found a 3fold increased risk with low lifetime sun exposure (12). Vitamin D is an important candidate implicated in PCa risk and its deficiency has been hypothesized to be a risk factor for PCa (13, 14). Reduced vitamin D levels correlate with established risk factors such as increasing age, African American ethnicity, and residence in northern latitudes (15). Cordera et al. also used diagnostic serum samples from blood to show that the risk of PCa decreased with higher levels of 1,25-dihydroxyvitamin D (6). The physiological and environmental factors that modify the supply of cutaneous vitamin D are levels of UV exposure, skin pigmentation, and polymorphism in the vitamin D receptor (VDR) gene ...

Insights into association between urolithiasis and prostate cancer

“…A study was done in African Americans where SNP1 and SNP4 in interaction with sun tanning showed 2 and 4 times increased chances of PCa cases respectively whereas SNP5 showed protective outcome by reducing the risk by 5%. Interestingly, among the reported SNPs, SNP2 and SNP6 showed no associations [18]. A genotype study found homologous loci for VDR rs2107301 and rs2238135 showed 2-2.5 times increased chance of risk for PCa [19].…”