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Genes Linked To Early Onset, Location Of Hereditary Colon Cancer

at individually, however, the age at diagnosis ranged from 26 years to 55 years. The average age of onset for colorectal cancer generally is 70 to 75 years.

Also in the group, proximal tumors (those located closer to the small intestine) were twice as common as distal tumors (those occurring closer to the rectum). This 2-to-1 ratio of proximal to distal tumors is typical of HNPCC, but why most people develop proximal tumors and some develop distal tumors has been unknown.

To explore why this variation in age of onset and tumor location exists, the researchers looked at three genes that produce enzymes for detoxifying cancer- causing, or carcinogenic, chemicals. These were the gene for N-acetyltransferase 1 (NAT1), and two forms of the glutathione S-transferase (GST) gene known as M1 and T1 (GSTM1 and GSTT1 respectively). Specifically, the researchers looked for the presence or absence of GSTM1 and GSTT1.

NAT1 is responsible for processing highly carcinogenic aromatic amines found frequently in the environment, in the diet and in cigarette smoke. The GST enzymes detoxify a variety of carcinogens and toxic drugs.

The researchers found that patients with one form of the NAT1 gene, known as NAT1- 10, and who were missing the GSTM1 and GSTT1 genes, tended to develop colorectal tumors at a younger age.

When the researchers looked at tumor location, they found that nearly half of patients with the NAT1-10 gene had distal tumors, which is significantly higher than the typical population of people with HNPCC.

People who had the GSTT1 gene also tended to have more tumors located in the distal colon than usual. There was no correlation between tumor location and the presence or absence of the GSTM1 gene.

Overall, said Peltomaki, "the presence of the NAT1-10 gene in individuals was associated with earlier tumor development and with distal location of the tumor."

Peltomaki and her colleagues are working to verify their findings in
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Contact: Paivi Peltomaki
Peltomaki-1@medctr.osu.edu
614-688-4493
Ohio State University
1-Feb-1999


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