© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 18, 1358-1365,
September 18, 2002
© 2002 Oxford University Press
ARTICLE |
Cancer Incidence in BRCA1 Mutation Carriers
Affiliations of authors: D. Thompson, D. F. Easton, Cancer Research U.K., Genetic Epidemiology Unit, University of Cambridge, United Kingdom.
Correspondence to: Douglas Easton, Ph.D., Cancer Research U.K., Genetic Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK (e-mail: douglas{at}srl.cam.ac.uk).
Background: Germline BRCA1 mutations confer a substantial lifetime risk of breast and ovarian cancer, but whether cancer at other sites is increased is less clear. To evaluate the risks of other cancers in BRCA1 mutation carriers, we conducted a cohort study of 11 847 individuals from 699 families segregating a BRCA1 mutation that were ascertained in 30 centers across Europe and North America. Methods: The observed cancer incidence was compared with the expected cancer incidence based on population cancer rates. Relative risks (RRs) of each cancer type in BRCA1 carriers relative to risks for the general population were estimated by weighting individuals according to their estimated probability of being a mutation carrier. All statistical tests were two-sided. Results: BRCA1 mutation carriers were at a statistically significantly increased risk for several cancers, including pancreatic cancer (RR = 2.26, 95% confidence interval [CI] = 1.26 to 4.06, P = .004) and cancer of the uterine body and cervix (uterine body RR = 2.65, 95% CI = 1.69 to 4.16, P<.001; cervix RR = 3.72, 95% CI = 2.26 to 6.10, P<.001). There was some evidence of an elevated risk of prostate cancer in mutation carriers younger than 65 years old (RR = 1.82, 95% CI = 1.01 to 3.29, P = .05) but not in those 65 years old or older (RR = 0.84, 95% CI = 0.53 to 1.33, P = .45). Overall, increases in the risk for cancer at sites other than the breast or ovary were small and evident in women (RR = 2.30, 95% CI = 1.93 to 2.75, P = .001) but not in men (RR = 0.95, 95% CI = 0.81 to 1.12, P = .58). Conclusions: In carriers of BRCA1 mutations, the overall increased risk of cancer at sites other than breast and ovary is small and is observed in women but generally not in men. BRCA1 mutations may confer increased risks of other abdominal cancers in women and increased risks of pancreatic cancer in men and women.
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