"People carrying BRCA1 or BRCA2 mutations already have their plates full managing a high risk of breast and ovarian cancer," says Stephen B. Gruber, M.D., Ph.D., a cancer geneticist in the U-M's Comprehensive Cancer Center. "The good news in our study is that they don't have to deal with an increased risk of colorectal cancer, as well."
Results of the study will be published in the Jan. 7 issue of the Journal of the National Cancer Institute.
Scientists have known for years that mutations in genes called BRCA1 and BRCA2 are associated with a much higher incidence of breast and ovarian cancer. Studies to determine whether BRCA mutations also increase the risk of colorectal cancer, however, have produced mixed and inconsistent results.
In the current study, Gruber and colleagues tested blood samples from 1,422 patients with colorectal cancer and 1,566 control subjects without colorectal cancer for mutations in BRCA1 or BRCA2.
Study participants were selected from the population-based Molecular Epidemiology of Colorectal Cancer (MECC) study in northern Israel - a collaboration between Gruber and Gad Rennert, M.D., Ph.D, of the Technion-Israel Institute of Technology Faculty of Medicine and Carmel Medical Center in Haifa, Israel. Colorectal cancer patients in the study were all treated at five major hospitals in northern Israel. They were matched with study participants without colorectal cancer who were of the same age, sex, ethnicity and from the same geographic area.
U-M scientists used DNA assays designed to identify three specific mutations in BRCA1 or BRCA2 genes. Called founder mutations, they are present in about 2.5 percent of men and women of Ashkenazi Jewish ancestry. Of the patients with colorectal cancer in the study, 1,002 were Ashkenazi Jews, as were 1,038 people without colorectal cancer.
"The advantage of working with founder mutations is that we know exactly where they occur in the DNA sequence, so it makes it makes it relatively easy to develop an assay to identify them," explains Bethany L. Niell, a student in the U-M Medical School's M.D./Ph.D. program, who was the paper's first author.
When they compared the results of DNA testing, U-M scientists found no statistically significant difference between the number of cancer patients with BRCA1 or BRCA2 mutations (24), and the number of non-cancer controls whose DNA contained one of these mutations (20).
"We found no strong common genetic basis between colorectal and breast cancer," says Gruber. "They are different diseases with different genetic factors."
In the second part of the study, scientists compared whether a family history of breast cancer in a parent, sister or daughter was associated with the development of colorectal cancer.
"We found no association between a family history of breast cancer in a first-degree female relative and an increased risk of colorectal cancer," says Gruber, an assistant professor of internal medicine and human genetics in the U-M Medical School and an assistant professor of epidemiology in the U-M School of Public Health.
"Population-based studies like the MECC study allow you to select patients and controls from the same general population," explains Niell. "Previous studies may have overestimated the risk of colorectal cancer because they used patients from high-risk families - those with a family history of breast or ovarian cancer - who may not be representative of the entire population."
While current national clinical care guidelines recommend informing BRCA1 and BRCA2 mutation carriers of an increased risk of colorectal cancer, Gruber says physicians should advise people with these mutations to follow colorectal cancer screening guidelines established for the general public. "Anyone over age 50 is at risk for colorectal cancer and screening save lives," he adds.
Colorectal cancer is the leading cause of deaths from cancer in Israel and the second leading cause of cancer deaths in the United States. Over 2,000 people are diagnosed with colorectal cancer in Israel each year, but incidence rates vary widely among different ethnic groups. Nearly 150,000 U.S. residents were diagnosed with colorectal cancer in 2002.
The research was funded by the National Institutes of Health. In addition to Gad Rennert, co-authors include Joseph D. Bonner and Lynn P. Tomsho from the U-M Medical School, and Ronit Almog, a study coordinator for the Molecular Epidemiology of Colorectal Cancer study in Haifa, Israel.
Journal of the National Cancer Institute, Vol. 96(1), Jan. 7, 2004