Heterozygosity of SNP513 in Intron 9 of the Human Calretinin Gene (CALB2) is a Risk Factor for Colon Cancer

Abstract

Background: The Ca²⁺-binding protein calretinin (CR), while absent in normal colonocytes, is expressed in the majority of poorly differentiated colon carcinomas, and is hypothesized that mutations in the distal part (from exon 7 to 10) of the CR gene (CALB2) could be responsible for the aberrant CR expression. Materials and Methods: Using PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, four single nucleotide polymorphisms (SNPs) were identified in CALB2 intron 9. Results: A significant positive association between the genotype at SNP513 and colon cancer was found: more C/T heterozygotes were found in patients with colon tumors (60%) compared to healthy controls (35%) or patients with lung tumors (38%). Our results indicate that C/T heterozygosity at position 513 is linked to CR expression in colon tumors and colon cancer cell lines, suggesting a link with increased carcinogenesis. Conclusion: The SNP513 in human CALB2 may thus be a predictive marker for colon tumors.