Genetic Makeup of Colon Cancer Tumors Varies among Whites, Blacks, Asians

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Colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer death in the United States. According to a recent study from Mayo Clinic researchers, the rate of survival for patients with stage III colon cancer varies with race. Strikingly, these racial disparities in survival persist despite uniform stage and treatment. The Mayo Clinic study analyzed data from more than 3 ,000 patients from a phase III trial, which included Asians, blacks, and whites. The results, published in the Journal of the National Cancer Institute, further reveal that the genetic makeup of colon tumors, and their frequency of mutation, also varies among races.

For the study, two cancer genes were analyzed, BRAF and KRAS, which have been associated with poor survival outcomes. BRAF mutation frequency in tumors from whites (13.9%) was twice that of tumors from Asians or blacks, while KRAS mutation rates were highest in tumors from blacks (44.1%). And BRAF/KRAS wild-type tumors were most common among Asians (66.7%).

Also, black patients younger than age 50 had shorter disease-free survival (DFS), compared with whites or Asians of any age. DFS is a composite endpoint of colon cancer recurrence or death from any cause.

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Harry Yoon, M.D.

“These findings put the issue more prominently on the radar of investigators that colon cancer biology may contribute to race-based disparities in survival,” says the study’s co-lead author Harry Yoon, M.D., an assistant professor of oncology at Mayo Clinic.

Plenty of literature has already examined social and economic factors as potential reasons for this disparity—late-stage diagnosis and decreased access to care, for example. “However, those factors are unlikely to adequately explain the study’s results,” says Dr. Yoon. “Because every patient analyzed was enrolled in the trial and therefore received very similar treatment and follow-up and had the same stage.”

A key finding of the study was that colon cancers among blacks under age 50 have more than double the risk of recurrence than whites. Almost half of younger black patients had colon cancer recurrence within five years, compared with 22 to 35 percent of white and Asian patients of any age.

“The high recurrence rate in young black patients is what’s driving the unfavorable DFS,” says Dr. Yoon. “I’m not aware of other data revealing that young black patients with stage III colon cancer, treated with modern chemotherapy, have a higher recurrence rate. It’s a major novelty of our study.”

Researchers adjusted for a number of potential confounders of this disparity, such as tumor grade; the degree of lymph node involvement; depth of tumor invasion; body-mass index; location of the tumor within the colon; history of smoking, obesity, or anomalies in mismatch repair genes; as well as BRAF/KRAS mutation status.

“The higher KRAS rate among black patients doesn’t adequately explain the survival disparities because young black patients still had the worst survival rate after we adjusted for KRAS and BRAF mutation status,” says Dr. Yoon.

It’s still too early for doctors to change the way they treat these patients, according to Dr. Yoon. More studies are needed to examine potential biological drivers of these differences more closely.

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Frank Sinicrope, M.D.

“We’re going to need to do some genetic profiling of the cancers,” says Frank Sinicrope, M.D., co-lead author of the study and professor of medicine and oncology at Mayo, “whereby we look at hundreds of thousands of genes and see if we can identify the genetic signatures, or profiles, that can distinguish the cancers by race. The main challenge will be interpretation of the data and trying to extract something meaningful from the results.”

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Justin Kreuter, M.D.

Justin Kreuter, M.D., is a clinical pathologist at Mayo Clinic in Rochester, Minnesota. His practice consists of both general and subspecialty aspects of clinical pathology. At Federal Medical Center-Rochester, Dr. Kreuter runs the general laboratory that supports a local in-patient population and does a large amount of reference work. At Mayo Clinic, Dr. Kreuter's time is split between the transfusion medicine service and transplant laboratory. In addition to clinical activities, his academic interests include several aspects of medical education, including teaching clinical judgement, frameworks for feedback, and reflection in medical practice.