Environmental Factors and Genetic Polymorphisms Associate with the Development and Prognosis of Oral Squamous Cell Carcinoma

Project: A - Government Institutionb - Ministry of Science and Technology

Project Details

Description

Background: Oral squamous cell carcinoma (OSCC) is a leading cause of morbidity and mortality especially among men in Taiwan. Accumulated evidence demonstrates the important role of genetic and environmental factors in the development and prognosis of OSCC. However, despite numerous studies, the genetic determinants of OSCC remain largely inconclusive. Aim: We aim to identify loci and environmental factors associated with development and prognosis of male OSCC, including assessments on gene-gene and gene-environmental interactions.Methods: A two-stage genome-wide association scan will be performed on an initial sample of 500 histologically confirmed male OSCC cases and 2000 age- and sex-matched healthy controls (1:4 ratio) of the Taiwanese ancestry using Affymetrix Axion Genome-Wide TWB Array Plate. Genetic association tests conducted in the case-control study will explore the development risk of OSCC using logistic regression models. Similar association tests conducted in a retrospective cohort study will evaluate the prognosis of OSCC using Cox proportional hazards regression models. In both instances, gene-gene and gene-environmental interactions will be tested. Based on significantly associated markers in the first stage, a replication sample of 1500 cases and 6000 controls will be genotyped using the iPLEX MassARRAY system. Findings from the previous two studies will then be validated in a joint analysis of 2000 cases and 8000 controls. Anticipated Results: From our previous work on the genome-wide scan, we speculated that the major pathologic pathway of OSCC in the Taiwanese population involves DNA repair. Based on these findings we are confident that our result will show significant loci mainly involved in the DNA repair and other important pathways, thus validating our speculation and results from other studies. In addition, we also intend to detect novel markers not found before that will be associated with OSCC. The findings from this study will aid in identifying more efficient screening, surveillance and management strategies for OSCC in Taiwan.
StatusFinished
Effective start/end date8/1/187/1/19

Keywords

  • Oral Squamous Cell Carcinoma
  • Environmental Factors
  • Genetic Polymorphisms
  • Development
  • Prognosis