The role of NOD1/CARD4 and NOD2/CARD15 genetic variations in lung cancer risk.

Background And Aim: NOD1/CARD4 and NOD2/CARD15 are members of the Nod-like receptor (NLR) family, and they contain a caspase recruitment domain (CARD). NLRs are located in the cytosol where they bind bacterial and viral ligands and play a key role in the innate and adaptive immune response, apoptosis, autophagy, and reactive oxygen species generation. NLR gene polymorphisms may shift the balance between pro- and anti-inflammatory cytokines and modulate the risk of infection, chronic inflammation, and cancer. NOD1/CARD4 and NOD2/CARD15 gene polymorphisms may also be associated with altered risks for many cancer types. The aim of our study was to evaluate the potential associations between lung cancer and NOD1/CARD4 and NOD2/CARD15 polymorphisms.

Method: The NOD1/CARD4 (rs5743336) and NOD2/CARD15 (rs2066847) SNPs were analyzed by PCR restriction fragment-length polymorphism analysis (PCR-RFLP) in 260 subjects (lung cancer patients: n = 160; healthy controls: n = 100) of Turkish origin. PCR products were digested with AvaI for rs5743336 and ApaI for rs2066847 and then visualized.

Results: Comparisons of the genotypes between control and lung cancer patients were performed by Chi-square tests. We found a significant difference in the genotypic distribution of the rs5743336 variant of NOD1/CARD4 between lung cancer patients and controls (p = 0.010, χ (2) = 9.220). However, we did not identify any statistically significant difference for the p.Leu1007fsX1008 (rs2066847) genotype of NOD2/CARD15 between groups (p > 0.05).

Conclusion: According to our data, the rs5743336 variant of the NOD1/CARD4 gene may influence the diagnosis and treatment of lung cancer, whereas the rs2066847 variant of the NOD2/CARD15 gene is not associated with lung cancer risk in the Turkish population.