Impact of Lifestyle factors and Genetic Variations of Nuclear and Mitochondrial Genes in Ampulla of Vater Carcinoma

Abstract

Cancer has surfaced as a lethal condition affecting people around the world. Ampulla of vater carcinoma (AVC) is a rare tumor that belongs to the gastrointestinal tumor family. Since AVCs are uncommon there is a dearth in evidence-based therapy for this tumor type. newlineDespite this, the tumor has a better prognosis when compared to other malignancies. Hence, a profound analysis of this tumor is necessary to develop novel therapeutic strategies to combat this condition. Further, it is essential to understand the underlying basis of this tumor to promote clinical trial specific to this cancer. This study predominantly focuses on the life style factors, molecular dysregulation of the PI3K pathway and mitochondrial variations that occurs in this cancer. This investigation revealed that alcohol consumption, smoking, consanguinity, education and locality had a significant relationship with occurrence of AVC. Chromosomal analysis also revealed some chromosomal anomalies in patients with AVC. Further, mutations were observed in the nuclear genes mTOR, TP53 and KRAS and mitochondrial gene MT-CO3, while no variations were uncovered in the nuclear gene NRAS and mitochondrial gene MT-ND1. Additionally, increased expression of the mTOR gene and acetylation of the KRAS promoter was also found in the AVC cohort. This report emphasizes on the involvement of the PI3K pathway in the tumorigenesis of AVCs. This will serve as a groundwork for more research encompassing AVCs. More AVC based research is imperative to develop drugs for treatment of AVC and for prescription of appropriate therapy for this tumor type. newlinei) Major objectives : newlineand#61623; To Identify the demographic profile and life style factors of AVC patients. newlineand#61623; To analyse the histopathology of AVC tumor tissue. newlineand#61623; To Identify chromosomal alteration by conventional cytogenetics (trypsin G banding) in AVC patients. newlineand#61623; To Identify gene mutations in PI3K pathway genes and mitochondrial genes in AVC tumor tissue. newlineand#61623; To analyse expression of PI3K pathway proteins by western blotting.