Heterozygosity of SNP513 in intron 9 of the human calretinin gene (CALB2) is a risk factor for colon cancer.

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. Using PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, four single nucleotide polymorphisms (SNPs) were identified in CALB2 intron 9. 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. The SNP513 in human CALB2 may thus be a predictive marker for colon tumors.