SNP-SNP Interaction in Genes Encoding PD-1/PD-L1 Axis as a Potential Risk Factor for Clear Cell Renal Cell Carcinoma.

PD-1/PD-L1 axis plays an important role in maintaining homeostasis and prevention from autoimmunity; however, in the tumor microenvironment, PD-1/PD-L1 interaction is responsible for the evasion of immune surveillance by tumor cells. We therefore hypothesized that single nucleotide polymorphisms (SNPs) in genes encoding PD-1 and PD-L1 molecules are associated with the development and outcome of renal cell carcinoma (RCC). Here we genotyped nine polymorphisms: five of PDCD1: rs36084323G>A, rs11568821G>A, rs2227981C>T, rs10204525G>A, rs7421861T>C and four of PD-L1: rs822335C>T, rs4143815G>C, rs4742098A>G, rs10815225G>C in 237 RCC patients (including 208 with clear cell RCC (ccRCC)) and 256 controls, with application of allelic discrimination method with use of TaqMan Assays. Interestingly, we found the SNP-SNP interaction between rs10815225 and rs7421861 polymorphisms associated with ccRCC risk. The rs7421861 TC genotype decreased the risk of ccRCC development compared to TT and CC genotypes in the group of rs10815225 GC + CC individuals (OR = 0.21, CI95% = 0.08; 0.54). While possessing of rs10815225 GC or CC genotype increased susceptibility to ccRCC when compared to rs10815225 GG genotype in individuals with rs7421861 TT or CC genotype (OR = 2.40, CI95% = 1.25; 4.61). In conclusion, genetic variants in PDCD1 and PD-L1 genes, especially taken together as SNP-SNP interactions, can be considered to be ccRCC risk factors.

Cancers. 2020 Nov 26*** epublish ***

Marta Wagner, Krzysztof Tupikowski, Monika Jasek, Anna Tomkiewicz, Agata Witkowicz, Kuba Ptaszkowski, Pawel Karpinski, Romuald Zdrojowy, Agnieszka Halon, Lidia Karabon

Laboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Ul. Weigla 12, 53-114 Wroclaw, Poland., Subdivision of Urology, Wroclaw Comprehensive Cancer Center, Pl. Hirszfelda 12, 53-413 Wroclaw, Poland., Department of Clinical Biomechanics and Physiotherapy in Motor System Disorders, Wroclaw Medical University, Ul. Grunwaldzka 2, 50-355 Wroclaw, Poland., Department of Genetics, Wroclaw Medical University, 50-367 Wroclaw, Poland., Department of Urology and Oncological Urology, Wroclaw Medical University, Ul. Borowska 213, 50-556 Wroclaw, Poland., Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Ul. Borowska 213, 50-556 Wroclaw, Poland.