Embargoed for release until 3 p.m. (CT) Tuesday, June 22, 1999
Deborah Pettibone, (716) 845-8593, [email protected]
PIONEERING STUDY TIES GENETIC FACTORS TO COLORECTAL CANCER IN AFRICAN AMERICANS
BUFFALO, NY - Novel genetic factors contribute to the incidence of colorectal cancer among a percentage of African-Americans, according to the results of a pioneering study conducted by a research team headed by Thomas K. Weber, MD, FACS, of the Division of Surgery, Roswell Park Cancer Institute. Their report will appear in the June 23, 1999 edition of the Journal of the American Medical Association.
This is the first study to analyze a group of African-American colorectal cancer patients for alterations in two genes (hMSH2 and hMLH1) linked to early age of onset and familial colorectal cancer in many other national and ethnic groups. In addition, each alteration detected was novel and had never been reported before. "Interestingly, the novel pattern of mutations observed in this study is reminiscent of the unique patterns of alterations seen in both the BRCA1 breast cancer gene and the APC gene among Ashkenazi Jewish patients," according to Dr. Weber.
Colorectal cancer is a serious public health challenge with more than 55,000 associated deaths estimated to occur in 1999. The challenge appears to be greater among African-Americans diagnosed with colorectal cancer who have a significantly increased risk of dying from the disease than Caucasians.
The objective of the study was to determine the frequency of germline alterations of the DNA mismatch repair genes - hMSH2 and hMLH1 - among affected members of African-American Hereditary Nonpolyposis Colorectal Cancer (HNPCC) families and early age of onset African-American colorectal cancer patients.
Eleven unrelated African-Americans diagnosed with histologically confirmed colorectal cancer enrolled in the Roswell Park Family Cancer Registry were evaluated. One patient is a member of an HNPCC family and the other 10 were diagnosed before age 50 and had no prior family history of colorectal cancer. "Mismatch repair gene associated early age of onset colorectal cancer in patients without a prior family history has been reported, but remains unstudied among African-Americans," notes Dr. Weber.
Germline mutations - hMSH2 (one patient) and hMLH1 (two patients) - were detected in 27% of the patients studied. "These results confirm that mismatch repair gene mutations contribute to colorectal cancer incidence in African-Americans and suggest that the pattern of germline mutations may be novel when compared to other racial and ethnic groups," according to Weber. "These findings also suggest that further study of mismatch repair gene associated colorectal cancer in African-Americans may facilitate clinical surveillance and contribute to colorectal cancer control in this high risk, understudied population."
The authors point out that mismatch repair gene associated colorectal cancer is probably not the explanation for the higher mortality among African-American patients. In fact, more than half of this excess mortality among African-Americans has been attributed to late stage diagnosis. "However, the observation that as much as 50% of the increased mortality sustained by this segment of the population is attributable to late stage diagnosis underscores the potential benefit that could be derived from increased clinical surveillance of members of this high-risk group in improving early stage diagnosis," concludes Dr. Weber.
Roswell Park Cancer Institute, founded in 1898, is the nation's first and one of its largest cancer research, treatment and education centers and is the only National Cancer Institute-designated comprehensive cancer center in Western New York.
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