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People with the mutation for hereditary hemochromatosis are at significantly higher risk for colon cancer

People who carry the mutation for hereditary hemochromatosis are 40 percent more likely than other people to develop colon cancer, according to an article in the January 15th issue of the Journal of the National Cancer Institute.

"Our findings are consistent with the view that taking in too much iron may be an environmental risk factor for colon cancer in some people," said Nicholas J. Shaheen, M.D., lead author of the study.

Iron is a pro-oxidant, which means high iron levels can lead to free radical formation and DNA damage, said Shaheen and his coauthors. The authors added that iron is an essential element for tumor cell growth and proliferation.

Mutations in the gene abbreviated as HFE are common, with a prevalence of roughly 15 percent of the U.S. population, according to Shaheen. Two such mutations investigated in the current study are strongly associated with the development of hereditary hemochromatosis. The gene itself encodes a cellular signaling protein that plays a role in iron metabolism.

"We don't fully understand why some people develop colon cancer and others do not," Shaheen said. "Our goal was to look for genetic risk factors for the disease that might be easily identifiable."

A total of 1,300 adults aged 40 to 79 years were involved in this population-based, case-control study, including people with and without colon cancer. Participants provided information on total iron intake and use of non-steroidal anti-inflammatory drugs. Blood samples were provided, and DNA was extracted and analyzed for the two major HFE mutations.

After controlling for age, race, gender, red meat consumption, non-steroidal anti-inflammatory drug use, and total iron intake, study participants with any HFE mutation were found to be 1.4 times more likely to have colon cancer than participants with no HFE mutation. The risk of colon cancer associated with an HFE mutation was similar for people with and without a family history of colon cancer. In addition, cancer risk increased with increasing age and total iron intake among people with an HFE mutation.

"When you have a high number of people with the mutation, and although the mutation itself confers only a mildly increased risk, the total number of cancers that may be attributed to HFE mutations could be fairly high," Shaheen said.

He added that further research on other populations is needed. "If we can develop a panel of adequate markers that really lets us identify a high-risk group, we can concentrate our colon cancer screening and surveillance in that group."


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