The Common polymorphisms in P21 and MDM2 genes as a risk factor for susceptibility and poor prognosis of non-small cell lung cancer in Iraqi population

Abstract

Background: Cyclin-dependent kinase inhibitor (P21/WAFI) and murine double minute 2 (MDM2) genes regulate cell growth. In malignant tumors, altered expression of these gene products is associated with poor prognosis, this study was designed to determine genotyping of P21 and MDM2. Methods: This case-control study included 140 lung cancer patients (101 males and 39 females) diagnosed with non-small cell lung carcinoma, matched with 150 healthy individuals(105 males and 45 females). The study was done between 2018 to 2022. The current study aimed to investigate P21-rs1801270 and MDM2-rs2279744 genes polymorphisms with lung cancer risk in the Iraqi population using the PCR-RFLP technique. Results: Compared with the P21-98 C and MDM2-309T genotypes, we found that P21-98A and MDM2-309G variants were associated with a high risk of NSCLC in Iraqi patients (OR= 5.0, C.I= 3.2-14.2, P<0.0001) for AA and (OR= 6.7, C.I= 4.0-12.4, P<0.0001)for GG. Also, AA and GG genotypes were associated with poor prognosis and significant associations were observed with a stage (p= 0.02) and metastasis status (p =0.003) for the P21 gene, (p= 0.01) and (p= 0.04) for the MDM2 gene respectively of NSCLC in elderly and smokers. Our results obviously showed the multiplicative interaction of P21 AA and MDM2 GG genotypes in the risk of developing lung cancer. Conclusions: The presence of AA variant alleles for p21 and GG for MDM2 increased the risk of lung cancer in males mainly those smokers older than 45. For this reason, these gene mutations may have a role as markers for susceptibility to lung cancer in those groups of people.