Research Introduction

The majority of human disease phenotypes are now believed to be of a complex nature, influenced by the presence of genetic variants and exposures to environmental factors. The inheritance of dominant predisposition genes, conferring a high cancer risk, has been demonstrated by the discovery of high penetrant predisposition gene mutations. Despite of their high penetrance, mutant alleles of such genes are relatively rare, accounting for only a small proportion of cancer cases. An emerging concept in genetics emphasizes the role of other rare and as well as common genetic variants in cancer risk. Single nucleotide polymorphisms (SNPs) are the major source of genetic variation in humans and inheritance of specific patterns of these SNPs are thought to contribute to cancer risk.

Disease-associated SNPs are hypothesized to alter the function and intrinsic properties of proteins involved in cancer-related pathways. A major challenge in this field involves the presence of enormous number of SNPs in the genome and the lack of functional studies to help us understand which ones are more likely to be candidates for cancer predisposition. In our laboratory, we have developed a genome wide approach to identify and characterize the functional consequences of SNPs from cancer related pathways. This strategy provides an invaluable source of functional SNPs to be utilized in disease association studies.