Effect of BRCA1 and BRCA2 on the association between breast cancer risk and family history

Elizabeth B. Claus, Joellen Schildkraut, Edwin S. Iversen, Donald Berry, Giovanni Parmigiani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1824-1829
Number of pages6
JournalJournal of the National Cancer Institute
Volume90
Issue number23
StatePublished - Dec 2 1998
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Claus, E. B., Schildkraut, J., Iversen, E. S., Berry, D., & Parmigiani, G. (1998). Effect of BRCA1 and BRCA2 on the association between breast cancer risk and family history. Journal of the National Cancer Institute, 90(23), 1824-1829.