The role of the Sirtuin in the pathogenesis of Lung Cancer

According to data of GLOBOCAN 2018, lung cancer is one of the most common types of cancer, it is also responsible for about one out of five of cancer deaths. It was discovered that in lung cancer, SIRT1 expression increased and correlated with poor prognosis and SIRT2 expression was decreased. While KRAS proto-oncogen mutations are mostly seen in lung adenocarcinomas, tumor suppressor gene p53 mutation and EGFR amplification and mutation are more common in small cell lung carcinoma. It is contemplated that increased expression and/or activity of SIRT1 may increase cancer risk by inhibiting p53 and potentially other tumor suppressor genes. In general, ıt was discovered tahat SIRT2 overexpression reduces cell proliferation and regulate cell death in response to DNA damage stress. In addition, it is known that SIRT2 deacetylate and regulate activity of KRAS proto-oncogene, which is common in lung adenocarcinomas. Mammalian sirtuins play an important role in cell resistance to stress and regulation of cell death. NAD + dependent deacetylase or mono-ADP-ribosyl-transferase activities of sirtuins are known. It regulates many cellular mechanisms by deacetylation of various transcription factors and enzymes. In mammals, the Sirtuin family has seven members that are localized in different cellular compartments and have various effects (SIRT 1-7). In this study, we investigated two polymorphisms (rs11596401 C / T, A and rs2015 A / C) in respectively SIRT1 and SIRT2, from Sirtuin family members. The study population composed of 100 patients with lung cancer and 100 healthy controls. Blood was collected into EDTA-containing tubes and genomic DNA was extracted. Genetic polymorphisms were detected by using polymerase chain reaction- based restriction fragment length polymorphism (PCR- RFLP) and the results were analyzed by chi-square test and logistic regression analysis. As a result of our analyzes, no statistically significant difference was found between genotype distribution (p=0.593) and allele distribution (p=0.617) for SIRT1 rs11596401 (C / T) gene polymorphism. According to our data for SIRT2 rs rs2015 (A / C) gene polymorphism, no significant difference was found between genotype (p=0.306) and allele distribution (p=1.0). As a result of our study, which investigated the relation between Sirtuin gene polymorphisms and lung cancer, no significant relation was found between SIRT1 rs11596401 (C/T) and SIRT2 rs2015 (A/C) gene polymorphisms and human lung cancer.