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August 10, 2005

Racial Differences in

JAMA. 2005;294(6):677-678. doi:10.1001/jama.294.6.677-b

In Reply: We agree with Ms Alford and Dr Mouchawar that a case-control study, an efficient and powerful method for identifying risk factors for a rare outcome, requires careful attention to study design and sampling issues.1,2 These issues were addressed in several ways. First, we defined a source population from which both cases and controls were sampled. The source population was the University of Pennsylvania Health System’s primary care population. Second, we restricted the source population to women with a first- or second-degree relative with breast or ovarian cancer. This restriction limited the ability to generalize our findings to women without a family history of cancer (a small minority of whom have a BRCA1/2 mutation) but increased study efficiency by ensuring that BRCA1/2 mutation risk was relatively balanced between cases and controls. Restricting the source population to women at even greater risk of carrying a BRCA1/2 mutation would have narrowed the gap in predicted mutation risk between cases and controls, but would have further reduced the study’s generalizability and prevented any evaluation of the association between mutation risk and use of BRCA1/2 counseling.