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Highly penetrant hereditary cancer syndromes


The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Approximately 5–10% of all cancers are inherited, the majority in an autosomal dominant manner with incomplete penetrance. While this is a small fraction of the overall cancer burden worldwide, the molecular genetic discoveries that have resulted from the study of families with heritable cancer have not only changed the way these families are counselled and managed, but have shed light on molecular regulatory pathways important in sporadic tumour development as well. In this review, we consider 10 of the more highly penetrant cancer syndromes, with emphasis on those predisposing to breast, colon, and/or endocrine neoplasia. We discuss the prevalence, penetrance, and tumour spectrum associated with these syndromes, as well as their underlying genetic defects.

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We are grateful to Doreen Agnese, Carrie Drovdlic, Heather Hampel, Rob Pilarski, and Leigha Senter for critical review of this manuscript. We thank Ross Waite for his assistance with electronic artwork. CE is the recipient of a Doris Duke Distinguished Clinical Scientist Award and is supported in part by the American Cancer Society, Department of Defense US Army Breast and Prostate Cancer Research Programs, Susan G Komen Breast Cancer Research Foundation, National Cancer Institute, National Institutes of Health, State of Ohio Biomedical Research and Technology Transfer Fund and V Foundation.

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Recently, it was reported that among seven unrelated cases of JPS individuals with germline MADH4 mutations, all were found to have hereditary haemorrhagic telangectasia (HHT) (Gallione et al., 2004).Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, Mitchell G, Drouin E, Westermann CJJ and Marchuk DA. (2004) Lancet, 363, 852–859.

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Nagy, R., Sweet, K. & Eng, C. Highly penetrant hereditary cancer syndromes. Oncogene 23, 6445–6470 (2004).

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  • inherited cancer susceptibility
  • familial cancer syndromes
  • breast cancer
  • colon cancer
  • endocrine neoplasia

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