Colon Cancer :: Gene changes increases colon cancer susceptibility in African Americans

Genetic variations in the body’s immune system could play a role in making African Americans more susceptible to developing colon cancer, scientists have found.

Researchers led by Krista Zanetti, Ph.D., a postdoctoral fellow in the National Cancer Institute’s Division of Cancer Prevention and Center for Cancer Research, looked at variations in genetic sequences of the gene that makes mannose-binding lectin (MBL), a protein that plays a role in inflammation and innate immunity. They compared 26 MBL variations, or single nucleotide polymorphisms (SNPs), in 261 colon cancer patients and 537 normal controls in the Baltimore area.

Of the 26, four SNPs were associated with a significant increase in colon cancer risk in African Americans, though not in Caucasians. African Americans who carried two copies of all four variants had an approximately six-fold higher risk of colon cancer compared to those without such variants.

The four DNA variants occur in linkage disequilibrium ? that is, they appear together at a higher frequency than by random chance ? in both African Americans and Caucasians, though they are more prevalent in the former. “It was surprising,” Zanetti said, “because we wouldn’t necessarily assume that any one SNP would be linked to one race more than others. It wasn’t our hypothesis.”

Zanetti and her team currently are attempting to validate the findings with data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial, a randomized control trial originally designed to test the effectiveness of cancer screening methods. They will screen the colorectal cancer patient subset of the study for the four SNPs, with individuals with colorectal polyps as controls. Both of the latter groups are mostly Caucasian.

“Before we validate these associations in African Americans, we first need to know whether or not they exist in Caucasians ? that’s the number one question we want to answer,” Zanetti said. “Is it possible that this is actually an African American risk factor?”

According to Zanetti, the PLCO study gives the researchers the high level of power needed to detect whether these associations really exist in Caucasians. That would then enable the team to design the rest of their study.

Zanetti noted that over the past three decades colon cancer deaths in African Americans have generally been higher than in Caucasians. “We don’t know why the decline in death rates has been smaller in African Americans, but we believe it’s more than one factor,” she said. “These SNPs aren’t necessarily the only answer. We need to keep working to uncover all the contributors to this increased risk, whether there are underlying biological issues or social determinants.

“We’re doing a multitude of functional studies in the laboratory to see if we can link a phenotype to the genotype we have found,” she said. “We’re trying to link it to biological function ? I think there’s more to it than just association.”

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