Association of 3' nearby gene BTLA polymorphisms with the risk of renal cell carcinoma in the Polish population

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.