BACKGROUND: Mutations in the BRCA1 and BRCA2 genes are associated with increased 
risk of breast, ovarian, and several other cancers. The purpose of the present 
study was to evaluate the incidence of cancer in first- and second-degree 
relatives of BRCA mutation carriers compared with the general population.
MATERIALS AND METHODS: A total of 1,086 pedigrees of BRCA mutation carriers was 
obtained from a prospectively maintained, internal review board-approved study 
of persons referred for clinical genetic counseling at the University of Texas 
MD Anderson Cancer Center. We identified 9,032 first- and second-degree 
relatives from 784 pedigrees that had demonstrated a clear indication of 
parental origin of mutation. Standardized incidence ratios (SIRs) were used to 
compare the observed incidence of 20 primary cancer sites to the expected 
incidence of each cancer based on the calculated risk estimates according to 
each subject's age, sex, and ethnicity.
RESULTS: BRCA1 families had increased SIRs for breast and ovarian cancer (p < 
.001) and decreased SIRs for kidney, lung, prostate, and thyroid cancer and 
non-Hodgkin's lymphoma (p < .001). BRCA2 families had increased SIRs for breast, 
ovarian, and pancreatic cancer (p < .001) and decreased SIRs for kidney, lung, 
thyroid, and uterine cancer and non-Hodgkin's lymphoma (p < .0025). Analysis of 
only first-degree relatives (n = 4,099) identified no decreased SIRs and agreed 
with the increased SIRs observed in the overall study population.
CONCLUSION: We have confirmed previous reports of an association between breast, 
ovarian, and pancreatic cancers with BRCA mutations. Additional research to 
quantify the relative risks of these cancers for BRCA mutation carriers can help 
tailor recommendations for risk reduction and enhance genetic counseling.
IMPLICATIONS FOR PRACTICE: BRCA gene mutations have been well described to carry 
an increased risk of both breast and ovarian cancer. However, the implications 
and risks of other cancers continues to be investigated. Evaluating the risks 
for other cancers further is key in identifying and managing risk reduction 
strategies.