Variants ofSCARB1andVDRInvolved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma

Abstract

The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC) based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in theSCARB1gene (OR=1.688, 95% CI: 1.104–2.582,P=0.016) and a haplotype inVDRcomprising positions rs739837, rs731236, rs7975232, and rs1544410 (P=0.012) to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation inGNAS1was implicated in a strong synergistic interaction withBIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy betweenGNAS1andSCARB1(P=0.036). Significance ofGNAS1-SCARB1interaction was further confirmed by logistic regression (P=0.041), which also indicated involvement ofSCARB1in additional interaction withEPAS1(P=0.008) as well as revealing interactions betweenGNAS1andEPAS1(P=0.016),GNAS1andMC1R(P=0.031),GNAS1andVDR(P=0.032), andMC1RandVDR(P=0.035).