Last year, researchers at University Hospital Seidman Cancer Center and Case Western University identified gene mutations that are unique to colon cancers in African-American patients, making it almost a different disease. Now, some members of that research team have found that tumors with such mutations are highly aggressive, with an increased likelihood of recurring and metastasizing.
The findings, published in the Journal of the National Cancer Institute, in the study “Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers,” may explain why African-Americans usually have more aggressive forms of colon cancer.
“This study is significant because it helps shed further light on why colorectal cancers are more aggressive in African Americans compared to other groups,” Joseph E. Willis, MD, chief of pathology at University Hospitals Case Medical Center, a professor of pathology at Case Western Reserve School of Medicine, and the study’s senior author, said in a press release. “While mortality rates for Caucasian men with colorectal cancer have decreased by up to 30 percent, they have increased by 28 percent for African American men since 1960.”
Although the factors that lead to such disparities between African-American and Caucasian patients are not fully known, Sanford Markowitz and colleagues thought the answer would mainly be found through genetic analysis.”We wondered if colon cancer is the same disease molecularly in African American individuals as it is in Caucasian individuals. Or could colon cancer be the same disease behaving differently in one population compared to another,” he said.
In the earlier study, researchers compared the gene signature of 103 colorectal cancer specimens from African-Americans with 129 samples from Caucasians, and found a panel of 15 genes that were significantly more mutated in the colorectal cancers of the African-American patient group.
“[That] study gave us our answer. Colon cancer in African American patients is a different disease molecularly,” Markowitz said.
Now, the research team examined 66 patients with Stage 1-3 colorectal cancer. They found that patients positive for one of the 15 previously identified mutations had a nearly three-fold increase in the rate of metastatic disease. Among patients with stage 3 colon cancer, those positive for the mutations were also nearly three times more likely to relapse, compared to patients without the mutations.
“This study builds on our previous genetic research on colorectal cancer,” said Markowitz, MD, PhD, a co-author and principal investigator of the $11.3 million federal gastrointestinal cancers research program (GI SPORE) that includes this study. “It illustrates the extraordinary impact that dedicated, collaborative teams can make when they combine scientific experience and ingenuity with significant investment.”
The researchers said more studies are needed to better understand how these mutations increase the risk for aggressive colorectal cancer, a key step to developing new therapies for these patients. They also recommend further research into whether these mutations are indicative of high risk in other ethnic groups, even if at lower frequency.