Copy Number Variant Genes as Risk Factors for Colorectal Cancer

Here we seek genetic factors associated with metachronous adenoma occurrence, hypothesizing that
genetic risk factors have been missed because association studies have sought risk-associated single
nucleotide polymorphisms, while ignoring structural variation causing gene copy number changes. Our
laboratory is looking for gene copy number variants that influence colorectal cancer risk using a number
of strategies:

  1. We are identifying candidate genes by using the Database of Genomic Variants to identify gene copy number variation (CNV) in genes in the vitamin D, polyamine and selenium pathways (Table 1).
  2. We have analyzed Illlumina genotyping data for evidence of CNV in previously genotyped candidate genes.
  3. We are experimentally determining candidate gene copy number status for individuals from two interventional trials using multiplex ligation-dependent probe amplification (MLPA).
  4. We will seek statistical associations between copy number genotype and adenoma recurrence, and will validate any associations in additional trial data.

By combining the data from these studies, we will increase power to discover individual gene copy
number variants and to investigate the association of each of these, along with a total genome
variation score, with the risk of adenoma recurrence.

Table1:Population Frequency of CNV in Candidate Genes

CNV chart updated.jpg