SNP analysis of nasopharyngeal carcinoma (NPC) associated genetic loci in LMP1 signalling pathway genes in tribal populations from North-Eastern India using computational methods

Abstract Background Nasopharyngeal carcinoma (NPC), a rare head and neck cancer, has distinct racial and geographic characteristics. It is considered rare in India, with the exception of a few endemic locations in the Northeast (NE), namely Manipur, Mizoram, and Nagaland. Genome-wide association studies (GWAS) indicate that NPC and the LMP1 signalling pathway may share disease processes. To gain a better understanding of the LMP1 signalling pathway, we looked at polymorphisms in the genes CHUK , PIK3CA , NFKBIA , TRAF3 and MAP2K4 , which are associated with the risk of NPC. Methods This study used whole exome sequencing (WES) to identify NPC-focused germline coding and non-coding changes in the three major NE tribal tribes (Mizoram, Manipur, and Nagaland) from 15 samples (9 cases and 6 controls). The Ion Proton™ platform was used to identify case and control variations. Case -control variants were then screened for quality control using Haploview. The significant variations were examined and compared to other clinical datasets. Results After segregating the variations, 22 of them were found to have passed Haploview filtering criteria. A variety of in-silico approaches were then utilised to process and filter these variants. We identified that one of the case-control variations might be associated with the risk factor for NPC in the NFKBIA region (NM_020529.3:c.336 + 104T > C) (ACMG criterion PP3). The identified NFKBIA variant represents a high-priority candidate for future Sanger sequencing validation in larger, independent cohorts to confirm its role as a definitive risk factor for NPC in this population’. Conclusion These data indicate that high-risk EBV and genes from the LMP-1 signalling pathway could have a combined effect on NPC. Given the limited sample size and the exploratory nature of the analyses, this study should be regarded as hypothesis-generating. To validate our findings, more study with larger independent samples and functional analysis is required.