GST is a big family of isoezymes, and based on their locations they can be divided into cytosolic and microsomal GST. The major role of this isozymes is to detoxify the chemicals. Mutations that alter the expression level or structure of the GST enzymes will impair the ability of removing the carcinogens and hence lead to cancer development. Many previous studies showed that cytosolic GSTs polymorphism is relate to cancers. This project is to investigate the correlations between the SNPs in microsomal glutathione-S- transferase (GST) gene and colon cancer....[ Read more ]

GST is a big family of isoezymes, and based on their locations they can be divided into cytosolic and microsomal GST. The major role of this isozymes is to detoxify the chemicals. Mutations that alter the expression level or structure of the GST enzymes will impair the ability of removing the carcinogens and hence lead to cancer development. Many previous studies showed that cytosolic GSTs polymorphism is relate to cancers. This project is to investigate the correlations between the SNPs in microsomal glutathione-S- transferase (GST) gene and colon cancer.

This is a case-control study. Blood samples were collected from 50 health volunteers, 50 sporadic colorectal cancer cases and 7 families. Genome DNA were prepared from the blood samples and subjected to analysis of the SNPs in the mGST-1 gene. Gene fragments were amplified from the promoter region and all the exons by polymerase chain reaction (PCR) using specific primers. The PCR fragments were purified and sequenced directly by dideoxy-chain termination method.

Seven, one and four SNPs were found in the promoter region, exon 2 and exon 4 respectively. Based on the predigree, some halpotypes in the promoter region and exon 4 were worked out for some family members. The correlations between the SNPs haplotypes and colon cancer were analyzed using statistical method. Chi-squares test was used to test the hypothesis. The SNP, SN70322, in exon 4 demonstrated a correlation with colorectal cancer (P = 0.009).

In exon 2, there were two SNPs occur in a colon cancer individual that lead to two amino acids subsitution. One subsitution is from non-polar amino acid to polar amino acid while the other is just opposite. Whether these subsitutions may impair the function of the mGST-1 enzyme, or the SNP in exon 4 can be used as a marker for colorectal cancer require further investigation.