Abstract LB-410: A single nucleotide polymorphism in human PIGK gene associates with low PIGK expression in colorectal cancer patients

Abstract Colorectal cancer (CRC) has one of the highest incidences of cancers worldwide and is the fourth most common cancer among men and women in the United States. In Israel, approximately 3000 new CRC cases are being diagnosed annually, representing 13% of all new cases. CRC ranks second in the total number of cancer cases both in the Jewish male and female population. It is uncommon in the non-Jewish (Arab) population. Phosphatidylinositol glycan, class K (PIGK) is an integral member of the Glycosylphosphatidylinositol transamidase (GPIT) protein complex that attaches a diverse group of macromolecules to the plasma membrane of eukaryotes. It is well established that PIGK catalyzes the endoproteolysis and amidation steps involved in transfer of a GPI-anchor to proteins. However, the role of PIGK in tumorigenesis remains largely unknown. Recently, we found a markedly low expression of PIGK protein in some colorectal cancer (CRC) patients. In order to understand the mechanism behind, we examined all the 10 exons of the PIGK gene by DNA sequencing and genotyping in 20 CRC patients from Israel (16 Jews and 4 Arabs). Corresponding expression of the PIGK protein was also determined by immunohistochemistry in all the above CRC patients. We found a single nucleotide polymorphism (C/C C/G or G/G; rs1048575) in the 3′UTR of the PIGK gene in 65% (13/20) of the CRC patients. Most of the patients with the altered genotype were Jews (12 vs. 1). Three out of four Arab patients (75%) exhibited the ancestral C/C genotype. We also observed a significantly low (P<0.002) expression of PIGK protein in all the patients with the altered allele (C/G or G/G) compared to the ancestral alleles (C/C). Similar observation was made on PIGK expression in a couple of transformed human colon cell lines with the ancestral (C/C) and altered (/C/G) genotype. Our results demonstrate for the first time a link between the SNP-1048575 and low PIGK expression in CRC patients and also suggest a possible association between altered PIGK expression and CRC susceptibility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-410.