Genetic Polymorphisms in Lung Cancer Susceptibility between Palestinian Population (Gaza Strip)

Abstract

Lung cancer is a leading cause of cancer-related deaths throughout the world. Recent GWAS and consecutive validation supported that SNPs in the 15q25, 5p15.33 and 6p22 regions showed significant association with lung cancer risk in multiple populations. Therefore, in this study six SNPs in three genomic regions were investigated because of their already established involvement in different populations. The relationship between these SNPs and smoking has been investigated. Methods: The SNPs rs16969968, rs1051730, rs402710, rs2736100, rs9295740 and rs4324798 were genotyped in a case-control study with 30 cancer cases and 60 age- and gender-matched cancer-free controls, all from Palestinian population of Gaza strip. Whole blood samples were collected from all subjects and relevant personal and clinical data was also collected from the participants and/or their medical record. Gene polymorphisms at the specified SNPs were determined by allele specific PCR and RFLP-PCR methodology. Results: The SNP rs16969968 G>A allele and rs1051730 C>T allele were found significantly related to lung cancer risk (P-value = 0.022, OR= 3.23; 0.001, OR=3.05 respectively). The allelic frequencies for the susceptibility alleles of rs16969968 and rs1051730 were higher in the cases than in the controls (36.7% vs 23.3% and 46.7 vs 22.5% respectively). Homo- and heterozygote nicotine consuming individuals have higher rate of cigarettes consumption in case of rs16969968 G>A (40.0±15.81 and 36.04±12.2 CPD compared to the wild type P-Value=0.006), and in case of rs1051730 C>T (39.17±15.62 and 33.00±10.36 CPD P-Value=0.015). The rs402710 has significant relation with lung cancer susceptibility (P-Value =0.015, OR= 3.00) between cases and controls. However, No statistically significant differences could be found in the distribution of rs402710 SNP between smoker control and smoker cases (P-value = 0.621). In addition, rs402710 T allele can be considered as risk allele for NSCLC. The rs2736100 was also associated with risk of lung cancer (P=0.044, OR= 4.33) and the frequency of the risk allele between cases and controls was 35% vs 18.3% respectively. However, it didn’t have correlation with smoking quantity (P- value = 0.269). Also, the rs9295740 distribution for the risk allele among case (30.0%) and control (15.0%) is not statistically significant (P-value = 0.075), but between the smoker cases and smoker controls is statistically significant (P-value = 0.016), so it may be risk factor for lung cancer between smokers. The allele frequency for rs4324798 was 20% in controls and 0.0% in cases, so it may have a role in protection from lung cancer. Conclusion: Our findings provide further evidence supporting the genetic variants in 15q25, 5p15.33 and 6p22 regions associated with the risk of lung cancer. Smoking and lung infections are important triggers for lung cancer. Further studies with larger cohorts of Palestinian lung cancer patients are recommended to extend the outcomes of this study.