Mutations in the BRCA1 tumor suppressor gene have been associated with a marked increase in the risk of breast and ovarian cancer. Several studies have examined the association of BRCA1 with other cancers, particularly prostate cancer and colon cancer, but the results have been mixed.
To clarify this connection, Deborah Thompson, Ph.D., and Douglas F. Easton, Ph.D., of the University of Cambridge, and their colleagues from the Breast Cancer Linkage Consortium estimated cancer risk rates among 11,847 people from families with a history of breast and/or ovarian cancer and in which at least one family member was a BRCA1 mutation carrier.
They found small but statistically significant increases in the risk of colon, liver, pancreatic, uterine, and cervical cancers among female BRCA1 mutation carriers, compared with the general population. In male BRCA1 mutation carriers, there was a slightly elevated risk of prostate cancer. However, this increase was seen only in men younger than age 65.
In the second study, Marcia S. Brose, M.D., Ph.D., and Barbara L. Weber, M.D., of the University of Pennsylvania Cancer Center, and their colleagues used a different method to estimate BRCA1-related cancer risks among 483 mutation carriers identified through a cancer risk counseling program. Some of the participants were the same ones used in the first study.
Over their lifetimes, BRCA1 mutation carriers had an estimated 73% risk of breast cancer and 41% risk of ovarian cancer, compared with risks of 13% and 2%, respectively, in the general population. In addition, mutation carriers had a small increase in risk of colon, pancreatic, and gastric cancers. Although the risk of fallopian tube cancer increased 120-fold, the authors point out that this cancer is extremely rare in the general population.
Stephen B. Gruber, M.D., Ph.D., of the University of Michigan, Ann Arbor, and Gloria M. Petersen, Ph.D., of the Mayo Clinic in Rochester, Minn., emphasize the importance of accuracy in estimating cancer risk among mutation carriers because these estimates influence choices regarding screening, chemoprevention, and prophylactic surgery.
"Both of these studies provide intriguing new patterns to investigate further, and it is now time for the next generation of studies to follow each lead more directly," they write in an accompanying editorial. "In the meantime, the message is that the major cancer risks conferred by BRCA1 are related to cancers of the breast, ovary, and fallopian tube, but increased risks of other cancers are likely to be small."
Contact: Douglas F. Easton, Ph.D., University of Cambridge, United Kingdom, 44-122-374-0160, Douglas@srl.cam.ac.uk
Olivia Fermano, University of Pennsylvania Cancer Center, 215-349-5653; fax: 215-349-8312, olivia.fermano@uphs.upenn.edu
Editorial: Kara Gavin, University of Michigan, 734-764-2220; fax: 734-615-2169, umhsmedia@umich.edu
Thompson D, Easton D, The Breast Cancer Linkage Consortium. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002;94:1358–65.
Brose M, Rebbeck T, Calzone K, Stopfer J, Nathanson K, Weber B. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 2002;94:1365–72.
Editorial: Gruber S, Petersen G. Cancer risks in BRCA1 carriers: time for the next generation of studies. J Natl Cancer Inst 2002;94:1344–5.
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