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Genetic anticipation and breast cancer: a prospective follow‐up study

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Abstract

Genetic anticipation is characterized by an earlier age of disease onset, increased severity, and a greater proportion of affected individuals in succeeding generations. The discovery of trinucleotide repeat expansion (TRE) mutations as the molecular correlate of anticipation in a number of rare Mendelian neurodegenerative disorders has led to a resurgence of interest in this phenomenon. Because of the difficulties presented to traditional genetics by complex diseases, the testing for genetic anticipation coupled with TRE detection has been proposed as a strategy for expediting the identification of susceptibility genes for complex disorders. In the case of breast cancer, a number of previous studies found evidence consistent with genetic anticipation. It is known that a proportion of such families are linked to either BRCA1 or BRCA2, but no TRE mutations have been identified. It has been shown that the typical ascertainment employed in studies purporting to demonstrate genetic anticipation combined with unadjusted statistical analysis can dramatically elevate the type I error. We re‐examine the evidence for anticipation in breast cancer by applying a new statistical approach that appears to have validity in the analysis of anticipation to data ascertained from a recent follow‐up of a large prospective cohort family study of breast cancer. Using this approach, we find no statistically significant evidence for genetic anticipation in familial breast cancer. We discuss the limitations of our analysis, including the problem of adequate sample size for this new statistical test.

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Authors and Affiliations

  1. Neurogenetics Section, Clarke Division, Center for Addiction and Mental Health, Toronto, Canada

    Andrew D. Paterson, David M.J. Naimark & Arturas Petronis

  2. Department of Statistics and Actuarial Science, The University of Iowa, Iowa City, IA, USA

    Jian Huang

  3. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Richard A. King & V. Elving Anderson

  4. Department of Health Sciences Research and Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN, USA

    Celine Vachon & Thomas A. Sellers

Authors
  1. Andrew D. Paterson
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  2. David M.J. Naimark
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  3. Jian Huang
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  4. Celine Vachon
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  5. Arturas Petronis
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  6. Richard A. King
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  7. V. Elving Anderson
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  8. Thomas A. Sellers
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Paterson, A.D., Naimark, D.M., Huang, J. et al. Genetic anticipation and breast cancer: a prospective follow‐up study. Breast Cancer Res Treat 55, 21–28 (1999). https://doi.org/10.1023/A:1006151132592

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