title: Variants of SCARB1 and VDR Involved 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 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).
authors.affiliation: Institute of Zoology, Faculty of Biology and Earth Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Cracow, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Pośpiech
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Ligęza
authors.affiliation: Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Garncarska 11, 31-115 Cracow, Poland.
authors.forename: Wacław
authors.initials: W
authors.lastname: Wilk
authors.affiliation: Institute of Zoology, Faculty of Biology and Earth Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Cracow, Poland.
authors.forename: Aniela
authors.initials: A
authors.lastname: Gołas
authors.affiliation: Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Garncarska 11, 31-115 Cracow, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Jaszczyński
authors.affiliation: Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Garncarska 11, 31-115 Cracow, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Stelmach
authors.affiliation: Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Garncarska 11, 31-115 Cracow, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Ryś
authors.affiliation: Institute of Zoology, Faculty of Biology and Earth Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Cracow, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Blecharczyk
authors.affiliation: Department of Dermatology, Collegium Medicum of the Jagiellonian University, Skawińska 8, 31-066 Cracow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wojas-Pelc
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jura
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Branicki
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D051122:Scavenger Receptors, Class B / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D018167:Receptors, Calcitriol; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C579457:VDR protein, human