Abstract
Abstract
Autozygosity is a term used to denote the presence of two identical haplotypes that are derived from an ancestor shared by both parents, so it essentially represents a special type of homozygosity. Runs of homozygosity (ROH) in the genome is a measure of the extent of autozygosity and is directly correlated with the extent of inbreeding. While the role of ROH in unmasking recessively acting mutations is well established in Mendelian genetics, much less is known about their contribution to more complex disorders such as cancer. Recently, it has been suggested that ROH may contribute to the risk of colorectal cancer (CRC) perhaps through the unmasking of a recessively acting CRC-predisposing mutations in one or more genes. However, this observation could not be replicated. In this study, we examine the role of homozygosity in the CRC risk by asking four specific questions. First, do CRC patients have enrichment for ROH in particular chromosomal regions compared to controls? Second, do CRC patients have longer ROH compared to controls? Third, is there a particular SNP that is more likely to be homozygous in CRC patients compared to controls? And fourth, are CRC patients more inbred than controls? By comparing 48 Saudi CRC patients to 100 ethnically matched controls, all processed on Affy 250SytI SNP Chip platform and analyzed by Partek, we found that the answer is no to all these four questions. We note here that this is the first study to address these questions in an inbred population so the negative results in our study carry more significance than what has been previously reported in the literature. We also note that our subgroup analysis of patients with MSI-positive tumors compared to other groups did not significantly change our results. While these results do not rule out the potential presence of recessively acting CRC-predisposing genes in a small percentage of patients that our relatively small sample size could not capture, they do suggest that such genes are unlikely to account for the disturbingly high incidence of CRC in our consanguineous population and that future research should consider other mechanisms.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3768. doi:10.1158/1538-7445.AM2011-3768