© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 1824-1829, Copyright © 1998 by Oxford University Press
EB Claus, J Schildkraut, ES Iversen Jr, D Berry and G Parmigiani
BACKGROUND: The discovery of BRCA1 and BRCA2 has led to a reassessment of
the association between family history of breast/ovarian cancer and breast
cancer risk after controlling for carrier status for mutations in the BRCA1
and BRCA2 genes. We examined whether family history of breast cancer
remains a predictive risk factor for this disease after carrier status for
BRCA1 and/or BRCA2 mutations is taken into consideration. METHODS: The data
are from 4730 case subjects with breast cancer and 4688 control subjects
enrolled in the Cancer and Steroid Hormone Study. The probability of being
a BRCA1 and/or BRCA2 gene carrier was calculated for each woman. Among
predicted noncarriers, logistic regression was used to assess the
relationship (odds ratios and 95% confidence intervals [CIs]) between case
or control status and family history of breast or ovarian cancer. Estimates
of age-specific breast cancer risk are presented by predicted carrier
status. RESULTS: Among predicted noncarriers, case subjects were 2.06 times
(95% CI = 1.69-2.50) and 1.24 times (95% CI = 1.17- 1.32) more likely to
report a first-degree or second-degree family history of breast cancer,
respectively, than were control subjects. Case subjects were 1.99 times
(95% CI = 1.63-2.44), 1.66 times (95% CI = 1.18-2.38), and 2.23 times (95%
CI = 0.21-24.65) more likely to report an affected mother, sister, or both,
respectively, than were control subjects. A family history of ovarian
cancer was not statistically significantly associated with breast cancer
risk. Noncarriers were predicted to have a lifetime risk of 9% of
developing breast cancer compared with a 63% risk for carriers.
CONCLUSIONS: Among women with a moderate family history of breast cancer,
i.e., predicted noncarriers of BRCA1 and/or BRCA2 mutations, family history
remains a factor in predicting breast cancer risk. In families with breast
and ovarian cancers, the aggregation of these two cancers appears to be
explained by BRCA1/BRCA2 mutation-carrier probability.
ARTICLES
Effect of BRCA1 and BRCA2 on the association between breast cancer risk and family history
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
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