Anna Partyka1, Krzysztof Tupikowski2, Anna Kolodziej2, Romuald Zdrojowy2, Agnieszka Halon3, Bartosz Malkiewicz2, Janusz Dembowski2, Irena Frydecka1, Lidia Karabon4. 1. Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, Wroclaw, Poland. 2. Department of Urology and Oncological Urology, Wroclaw Medical University, Wroclaw, Poland. 3. Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland. 4. Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, Wroclaw, Poland; Department of Urology and Oncological Urology, Wroclaw Medical University, Wroclaw, Poland. Electronic address: lkarabon@iitd.pan.wroc.pl.
Abstract
OBJECTIVE: T cells play an important role in antitumor immunity, and molecules regulating T-cell activity could influence cancer susceptibility. The distinct role of coinhibitory receptors in immunosurveillance has been considered. B- and T-lymphocyte attenuator (BTLA) is one of these receptors, which negatively regulate immune responses. The aim of this study was to investigate the association between BTLA gene polymorphisms and susceptibility to renal cell carcinoma (RCC) in the Polish population. METHODS: Altogether 282 patients with RCC and 480 healthy subjects were genotyped for the following polymorphisms: rs2705511, rs1982809, rs9288952, rs16859633, rs9288953, rs2705535, and rs1844089 using the TaqManSNP Genotyping Assays. RESULTS: Here, we found that the presence of rs1982809G allele (genotype GG+AG) is associated with increased risk of RCC (odds ratio = 1.38; 95% CI: 1.03-1.86; P = 0.03). In patients with clear-cell RCC (ccRCC) with high-grade (3 and 4) tumors, the frequency of rs1982809[GG] genotype was significantly higher as compared to those with low-grade (1 and 2) tumors and to the controls (0.14 vs. 0.06, P = 0.05 and 0.14 vs. 0.06, P = 0.04, respectively). Moreover, we have noticed the trend for overrepresentation of carriers of rs2705511C allele in patients with RCC as compared with the controls (0.51 vs. 0.44, P = 0.08) Haplotype rs2705511C/rs1982809G/rs9288952A/rs9288953T/rs2705535C/rs1844089G (CGATCG) increased the risk of RCC of 46% (odds ratio = 1.46; 95% CI: 1.08-1.96; Pcorrected = 0.05). CONCLUSION: Our results indicate that polymorphisms rs1982809 situated in 3' UTR nearby region of BTLA gene might be considered as low-penetrating risk factor for RCC, but results have to be confirmed in further studies.
OBJECTIVE: T cells play an important role in antitumor immunity, and molecules regulating T-cell activity could influence cancer susceptibility. The distinct role of coinhibitory receptors in immunosurveillance has been considered. B- and T-lymphocyte attenuator (BTLA) is one of these receptors, which negatively regulate immune responses. The aim of this study was to investigate the association between BTLA gene polymorphisms and susceptibility to renal cell carcinoma (RCC) in the Polish population. METHODS: Altogether 282 patients with RCC and 480 healthy subjects were genotyped for the following polymorphisms: rs2705511, rs1982809, rs9288952, rs16859633, rs9288953, rs2705535, and rs1844089 using the TaqManSNP Genotyping Assays. RESULTS: Here, we found that the presence of rs1982809G allele (genotype GG+AG) is associated with increased risk of RCC (odds ratio = 1.38; 95% CI: 1.03-1.86; P = 0.03). In patients with clear-cell RCC (ccRCC) with high-grade (3 and 4) tumors, the frequency of rs1982809[GG] genotype was significantly higher as compared to those with low-grade (1 and 2) tumors and to the controls (0.14 vs. 0.06, P = 0.05 and 0.14 vs. 0.06, P = 0.04, respectively). Moreover, we have noticed the trend for overrepresentation of carriers of rs2705511C allele in patients with RCC as compared with the controls (0.51 vs. 0.44, P = 0.08) Haplotype rs2705511C/rs1982809G/rs9288952A/rs9288953T/rs2705535C/rs1844089G (CGATCG) increased the risk of RCC of 46% (odds ratio = 1.46; 95% CI: 1.08-1.96; Pcorrected = 0.05). CONCLUSION: Our results indicate that polymorphisms rs1982809 situated in 3' UTR nearby region of BTLA gene might be considered as low-penetrating risk factor for RCC, but results have to be confirmed in further studies.