Iron overload gene tied to colon cancer increased risk

CHAPEL HILL — Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that people with gene mutations associated with abnormally high iron levels are 40 percent more likely than others to develop colon cancer.

A report of the research published in the Journal of the National Cancer Institute today (Jan. 15) found the cancer risk greater in mutation carriers who are older or who consume high quantities of iron.

“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 study lead author Dr. Nicholas J. Shaheen, assistant professor of medicine and assistant professor of epidemiology in the UNC School of Public Health.

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

People inherit two copies of a gene known as HFE, one from each parent. Mutations to the gene are common, occurring in an estimated 15 percent of the U.S. population, Shaheen said. Two such mutations investigated in the study are strongly associated with the development of hereditary hemochromatosis, a condition characterized by iron overload and that leads to problems of the pancreas, liver, heart and other organs. 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.”

Thirteen hundred adults, ages 40 through 79, 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 (NSAIDs). Blood samples were provided, and DNA was extracted and analyzed for two major HFE gene mutations.

After controlling for age, race, gender, red meat consumption, NSAID use and total iron intake, study participants with any HFE gene mutation were found to be 1.4 times more likely to have colon cancer than participants with no HFE gene mutation. The risk of colon cancer associated with an HFE mutation was similar for those who did and did not have a family history of colon cancer. And among people with HFE mutations, cancer risk increased with increasing age and with total iron intake.

“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.”

Shaheen’s UNC co-authors include Drs. Lawrence Silverman and Elizabeth Rohlfs from the department of laboratory medicine and pathology; Drs. Robert Sandler, Laura Lawrence and Temitope Keku from the Center for Gastrointestinal Biology and Disease and the division of digestive diseases and nutrition; and Drs. Joseph Galenko and Christopher Martin, also from the Center for Gastrointestinal Biology and Disease.