Abstract 198P
Background
Importance of immune checkpoints molecules in NSCLC was proven by the introduction of blockade of these receptors in routine treatment. B and T lymphocyte attenuator (BTLA) is another immune checkpoint molecule that regulates immune response. Our previous studies showed a significant association between BTLA gene variants and susceptibility to renal cell carcinoma and chronic lymphoblastic leukemia. The aim of this study was to verify the hypothesis that BTLA polymorphic variants are associated with susceptibility to NSCLC.
Methods
Genomic DNA was isolated from the venous blood of 384 patients diagnosed with NSCLC and 475 controls. Using TaqMan probes we genotyped seven BTLA SNPs: rs1982809, rs1844089, rs9288952, rs9288953, rs2705511, rs2633582, and rs11921669 on ViiA 7 Real-Time PCR System.
Results
Statistical analysis of genotypes and alleles distributions for all investigated BTLA SNPs showed that SNP rs1982809 may be associated with susceptibility to NSCLC. In particular presence of G allele at rs1982809 (AG+GG genotypes) was more frequent in NSCLC group compared to controls (38.8% vs 45.3%, p=0.056). Allele distribution showed that the presence of allele G in rs1982809 significantly increases NSCLC risk (OR=1.25, p=0.046). For other studied SNPs in the overall analysis, we did not observe differences between NSCLC patients and controls. However, in the subgroup analysis we found that in patients with adenocarcinoma (AD) genotypes distribution of rs1982809 was significantly different between AD patients and controls (p=0.048). Moreover, we noticed the trend for overrepresentation of rs2705511[C] allele (AC+CC genotypes) in patients with AD compared to controls (43.4% vs 53%, p=0.079). After stratification by gender, we observed an association between the presence of rs9288953[T] and NSCLC susceptibility (p=0.004) in females. The global distributions of the haplotypes did not differ significantly between the cases and controls. However, we noticed that the global distribution of the haplotypes differs significantly between the never-smokers and smokers (p=0.0003).
Conclusions
Results of our study show that rs1982809 in BTLA gene might be considered a low penetrating risk factor for NSCLC susceptibility in the Polish population.
Legal entity responsible for the study
Laboratory of Genetics and Epigenetics of Human Diseases.
Funding
National Science Center Poland OPUS17 2019/33/B/NZ5/03029.
Disclosure
All authors have declared no conflicts of interest.