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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 the  SCARB1  gene (OR = 1.688, 95% CI: 1.104–2.582,  P  = 0.016) and a haplotype in  VDR  comprising 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 in  GNAS1  was implicated in a strong synergistic interaction with  BIRC5 . This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between  GNAS1  and  SCARB1  ( P  = 0.036). Significance of  GNAS1-SCARB1  interaction was further confirmed by logistic regression ( P  = 0.041), which also indicated involvement of  SCARB1  in additional interaction with  EPAS1  ( P  = 0.008) as well as revealing interactions between  GNAS1  and  EPAS1  ( P  = 0.016),  GNAS1  and  MC1R  ( P  = 0.031),  GNAS1  and  VDR  ( P  = 0.032), and  MC1R  and  VDR  ( P  = 0.035).

biomed research international

Variants of<i>SCARB1</i>and<i>VDR</i>Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma

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