considering getting tested:
7 December 2006
BRCA prevalence, impact underestimated
BRCAgene mutations are more prevalent than previously thought and predispose to a wide variety of cancers, researchers have found.
About 1% of the general population in Ontario, Canada, harbor BRCA mutations, the researchers estimate, and these appear to multiply the risk of testicular and pancreatic as well as breast and ovarian cancer.
The team recommends that BRCA mutations "should be suspected in families with breast, ovarian, and various other cancers in male relatives as well as female."
Knowledge of the proportion of people carrying mutations in BRCA1 and BRCA2 and the associated cancer risk "is important for genetic screening and counseling," Harvey Risch (Yale University School of Medicine, New Haven, Connecticut, USA) and colleagues note.
To investigate, they studied the results of screening for germline BRCA mutations in 1171 women who were diagnosed with ovarian cancer in Ontario between 1995 and 1999, and studied the incidence of cancer in 8680 of the women's first-degree relatives.
Among the 977 participants with invasive ovarian cancer, 75 had mutations in BRCA1 and 54 in BRCA2, giving an overall mutation prevalence of 13.2%, the researchers report in the Journal of the National Cancer Institute.
Using these values and the relative risk of cancer estimated for the probands' relatives, Risch et al calculated the frequencies of mutation carriage in the general population of Ontario.
Carriage of BRCA1 mutations was linked to a 21-fold increased risk of ovarian cancer, an 11-fold increase in female breast cancer, and a 17-fold increased risk of testicular cancer. Novel associations were also made with the BRCA2 mutation, which was linked to 4.6-fold increase in male and female breast cancers and a 6.6-fold increase in pancreatic cancer, alongside a seven-fold increase in ovarian cancer.
The team also assessed how the location of mutations within the coding sequence of the BRCA genes influenced the associated risk. "For BRCA2, compared with no mutation, we found increased risk [for breast cancer] associated with mutations outside of the ovarian cancer cluster region (OCCR) but not with mutations in the OCCR," they report.
If confirmed, this finding indicates that "patients carrying such mutations may be able to avoid disfiguring prophylactic mastectomy," the team notes.
"Our lifetime ovarian cancer penetrance estimate for BRCA2 mutations is also low and indicates that women with BRCA2 mutations may be able to delay prophylactic oophorectomy until menopause," Risch and colleagues conclude.
J Natl Cancer Inst 2006; 98: 1694-1706
http://jncicancerspectrum.oxfordjour...nci;98/23/1694
© 2006 CMG