Constructing Susceptible Nucleotide Polymorphism Panel for Multiple Primary Cancers in Oral Cavity Cancer Patient

Oral squamous cell carcinoma (OSCC) is one of the leading causes of morbidity and mortality especially among men in Taiwan. Due to the habitual use of cigarette, alcohol and areca quid (AQ) in Taiwan, the mucosa of upper aero-digestive tract undergoes pre-malignant alterations and has higher chance to turn into malignancies. Fifteen percent of OSCC patients develop multiple primary tumors (MPTs) either synchrously or metachronously. The MPTs occur 70% in oral cavity, and the rest in oropharynx, hypopharynx, esophageus and others. Early detection of MPTs is important. Selecting high risk patients who are vulnerable to develop MPTs by susceptible gene analysis is of clinical significance.In this 3-year project, we will focus on a whole genome searching of high-risk gene polymorphisms that are most related with MPTs in OSCC patients. A high risk gene panel will be built from our analysis and validated in a large OSCC sample database.In the first and 2nd year of this project, one-to-one study design will be adopted (600 cases vs 600 controls) in whole genome screening. The cases will include 3 subsets: first is 200 cases of oral pre-malignancies, 2nd is histologic confirmed OSCC patients without multiple primary cancer, and 3rd is OSCC patients who were confirmed the development of multiple primary cancers. Six hundred normal controls will be from Taiwan Biobank and our serum database for genetic analysis. The environmental exposures will be recorded by questionnaire. A genome-wide association scan on Taiwanese ancestry will be performed by using Affymetrix Axion Genome-Wide TWB 2.0 Array Plate. Nucleotide polymorphism markers for MPTs will be selected by logistic regression under the additive genetic model. Susceptible polymorphism gene panels for MPTs will be generated by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and incorporating gene-environment interaction. In the 3rd year of the project, susceptible genes polymorphism panels will be tested in an independent sample set (1200 cases). The susceptible gene polymorphism panels will be further genotyped and compared by receiver-operator characteristic curves (ROC) and the C statistics. As such, a best-fit panel will be built from the analysis.Hopefully, susceptible gene polymorphisms for MPTs will be picked out and build a risk assessment panel in our 3-year project. The panel will help clinicians identify high risk patients for screen, surveillance and management in a more efficient manner in Taiwanese OSCC for the development of MPTs.

Project ID:PC10907-1215
External Project ID:MOST109-2314-B182-015