AT-rich interaction domain 1A gene polymorphisms and their genetic association: A possible impact on Gastric cancer risk in North India

Abstract

Background: AT-rich interaction domain containing protein 1A (ARID1A), has recently emerged as a novel class of gene which acts as a potent tumor suppressor in numerous types of cancers such as Gastric, Breast, Ovarian, Colorectal, Lung cancers. ARID1A is involved in the regulation of various cellular processes such as proliferation, differentiation and DNA repair, yet its association with the susceptibility of cancer remains unknown.

Objective: Here, we aimed to analyse the association of the ARID1A variants (Pro912Thr, Gln944Lys and Gln920Ter) with the risk of Gastric cancer (GC) in Kashmiri population.

Participants: The study included 103 confirmed cases of GC and 163 normal controls.

Study design & Methods: The genotypes were studied using Polymerase Chain Reaction. Different bioinformatic predictive tools were also used to analyse the possible effect of these SNP’s on the resultant protein.

Results: The Pro912Thr and Gln920Ter variants of ARID1A showed significant difference in genotypic and allelic frequencies between the GC cases and controls (P < 0.05), whereas, the data did not reveal any correlation between Gln944Lys variant and Gastric cancer risk. Both Pro912Thr and Gln920Ter SNP’s follow “Dominant mode of inheritance”. In Silico analysis predicted that amino acid substitution of Pro912Thr SNP decreases the protein stability thus changing the functional properties of resultant protein, so backing the possibility of damaging effect of this SNP.

Conclusion: Our study suggests that Pro912Thr and Gln920Ter SNP’s of ARD1A gene are associated with increased risk of GC in Kashmiri population.