Jornal de Biomarcadores Moleculares e Diagnóstico

A Significant Association of IL1R2 DraIII T/G Polymorphism with the Risk of Gall Bladder Cancer in Ethnic Kashmiri Population

Abstract

Malik Gawharul Haq, Sabzar A Malik, Imtiyaz A Bhat, Sadaf Ali, Arshad A Pandith, Omer J Shah and Zafar A Shah

Background: Chronic inflammation is considered as an emerging area of research interest because of its cognize association with different organ cancers. Recent advances in cancer research have substantiated that targeting cytokines have a strong therapeutic potential in reducing the mortality of inflammation-related cancers. Gallbladder cancer (GBC) has been consistently associated with inflammation mostly due to presence of gallstones which prelude inflammatory response. The Interleukin-1 (IL1) gene cluster serves an important function of immunomodulation, thereby regulating interplay between inflammation and cancer. Studies on the association of IL1 polymorphisms with GS and GBC have shown drastic variations in different populations. Since no such study has been carried out in ethnic Kashmiri population which is known for high incidence of GS disease, we aimed to evaluate the possible role of pro-inflammatory IL1 family in the pathogenesis of GBC and GS disease. Methods: A total of 370 individuals (120 GBC, 120 GS and 130 healthy controls) were prospectively recruited. The study analyzed various polymorphisms of IL1 gene family to predict their association with GBC and gallstone disease. PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) was used for genotyping and SPSS 23.0 software was used to calculate odds ratios (ORs) and confidence intervals (CIs). Tissuespecific expression of IL-1α was done by Quantitative Real-time PCR (qRT-PCR) and the data was analyzed by Graph Pad Prism version 5. Results: IL1R2 T/G DraIII 'GG' genotype (OR: 2.65, 95% CI: 1.27-5.53, P=0.011) and 'G' allele (OR: 1.57, 95% CI: 1.10-2.24, P=0.014) indicated a positive association with GBC. Two polymorphisms in the IL1 gene family (IL-1α +4845G/T and IL1R1Pst1C/T) were observed to be insignificant towards GBC in our study cohort. IL-1α mRNA expression did not differ between tumor and adjacent normal GB tissues. Above all none of the studied polymorphisms was significant towards gallstone disease. Conclusion:  We conclude that IL1R2 DraIII T/G SNP bears a significant association with GBC and could be an important etiological factor for GBC in our population.