Effects of Genetic Susceptibility Variants on the Risk of Pancreatic Cancer and the Two-way Interactions between Single Nucleotide Polymorphisms (SNPs) Open Access

Tao, Biwen (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/6t053g67b?locale=en


Pancreatic cancer is one of the most lethal cancers, with an estimated 5-year relative survival rate of 6% in the United States, the lowest among all cancer sites. Although the etiology of pancreatic cancer is still not clear, an increasing number of studies suggest that genetic mutations are associated with pancreatic carcinogenesis. In contrast to mutations with significant functional consequences on the protein, SNPs have been considered as functionally insignificant. Even though the individual effect of a SNP is relatively limited, the additive effect of the combinations of functionally related SNPs may synergistically contribute to risk of pancreatic cancer. Previous genome-wide association studies (GWAS) identified a pancreatic cancer susceptibility locus on chromosome 13q22.1, which was considered to be specific for pancreatic cancer. In order to evaluate the risk of pancreatic cancer contributed by individual SNPs, this study investigated 39 SNPs from 14 important genes and 1 highly associated non-genic locus, based on established evidence from published studies and their availability in the PanScan dataset. To better understand the role of SNPs on non-genic region of chromosome 13q22.1 that is specifically associated with pancreatic cancer, this study also assessed the interaction between these two SNPs with other selected susceptibility variants. After adjusting for age and sex, significant associations are observed between 13 SNPs and the risk of pancreatic cancer. A positive additive interaction between rs9564966 on 13q22.1 and rs3790844 on NR5A2 is identified on the risk of pancreatic cancer, with relative excess risk due to interaction (RERI) of 1.56. Further investigation of this interaction is required to evaluate the probability of false positive.

Table of Contents

Introduction. 1

Background. 1

Specific Aims. 5

Methods. 6

Study Population. 6

Data Collection. 6

Definition of Variables. 6

Statistical Analysis. 7

Ethics Approval. 7

Results. 8

Characteristics of Study Population. 8

Association of Individual SNPs and Risk of Pancreatic Cancer. 8

Two-way Interaction between SNPs. 14

Discussion. 16

References. 18

About this Master's Thesis

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
  • English
Research Field
Committee Chair / Thesis Advisor
Last modified

Primary PDF

Supplemental Files