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To the Editor: Dr de la Hoya and colleagues¹ found that in families with breast and/or ovarian cancer, mutations in BRCA1 but not BRCA2 were associated with a sex ratio skewed against male births. However, because the authors did not assess for several possible sources of confounding, their results may not permit the conclusion that BRCA1 mutations are associated with an asymmetrical sex ratio. The highly penetrant breast and ovarian cancer in BRCA1 families is an example of an autosomal dominant sex-limited phenotype. That is, only females carrying a BRCA1 mutation can develop ovarian cancer, and the majority of cases of breast cancer in families with the BRCA1 mutation also occurs in females.

Thus, the finding that more female offspring are seen in BRCA1 pedigrees is more likely to be explained by ascertainment bias than a true sex-ratio distortion. Families in this study were ascertained by the presence of 3 . . . [Full Text of this Article]

Matthew E. Mealiffe, MD
Department of Medicine
University of Washington
Seattle

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