A team of scientists at Memorial Sloan-Kettering Cancer Center and the University of Michigan collaborated with colleagues in the United States and at the Carmel Medical Center/Technion University in Israel to test whether the mutation, called BLMAsh, plays a role in the development of cancer.
The investigators analyzed the frequency of BLMAsh mutations in 1,244 colon cancer patients from New York City and Israel, and compared this frequency to that observed in 1,839 healthy volunteers. Almost two percent of the patients with colon cancer were found to carry the mutation compared to less than one percent of the healthy individuals in the study.
"The interesting aspect of this study is the discovery of a possible novel pathway for colon cancer in humans, which had not previously been suggested in laboratory models," said Kenneth Offit, MD, Chief of the Clinical Genetics Service at Memorial Sloan-Kettering, and senior author of the paper.
It was previously known that persons with mutations affecting both of their BLM genes were at increased risk for colon cancer. "However, this is the first study to show that individuals carrying a single BLM mutation are at increased risk for colon cancer," commented Nathan Ellis, PhD, Director of the Laboratory of Cancer Susceptibility at Memorial Sloan-Kettering and a lead author of the study.
In 1995, Dr. Ellis and colleagues cloned the BLM gene, alterations of which cause Bloom's syndrome, a rare genetic disorder associated with a predisposition to cancer. The current study focused solely on individuals of Ashkenazi Jewish origin because a single BLM mutation, BLMAsh, is most common in this group. About one in 100 healthy individuals of Ashkenazi ancestry carry the BLMAsh mutation.
"Although the finding that BLM mutations are associated with colon cancer risk pertains only to those of Ashkenazi Jewish ancestry, we feel the scientific implications are relevant to understanding the fundamental genetic mechanisms that cause colon cancer in the general population," said Dr. Offit.
The researchers at Memorial Sloan-Kettering also analyzed the frequency of the mutation in 960 Ashkenazi patients with cancers of the breast, uterus, ovary, prostate, and lymphoid organs. They saw no increased risk for cancers at these sites associated with the BLMAsh mutation, suggesting that the BLM pathway may be of special relevance in colon tumor formation.
The authors plan to conduct additional studies to determine molecular mechanisms whereby mutations in BLM lead to the formation of colon cancer. They also plan to study how likely individuals who carry the mutation are to develop pre-cancerous lesions called polyps. These lesions may be found and removed by screening procedures such as colonoscopy.
The researchers caution that testing for the BLM mutation should only be performed in the context of clinical trials, since medical and family history are still the best guide to recommendations on cancer screening.
Researchers from the University of Cincinnati, North Shore Long Island Jewish Research Institute, Columbia University, and the National Cancer Institute also contributed to this research, which was supported by the National Cancer Institute, the Academic Medicine Development Company of New York (AMDEC), the Irving Weinstein Foundation, the Lymphoma Foundation, the Cancer Research Foundation of America, and the Frankel Fellowship Fund.
Memorial Sloan-Kettering Cancer Center is the world's oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Throughout its long distinguished history, the Center has played a leadership role in defining the standard of care for patients with cancer.
EDITOR'S NOTE: To speak with Dr. Stephen Gruber, Assistant Professor of Internal Medicine and Epidemiology at the University of Michigan Medical School, and a lead author of the paper, please contact Sally Pobojewski at 732-615-6912.
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