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Familial prostate cancer: the damage done and lessons learnt

Nature Reviews Urology volume 10, pages 116–122 (2013)Cite this article

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Abstract

Background. A 51-year-old French Canadian man presented to his family physician owing to an extensive family history of prostate cancer in five brothers, his father and two paternal uncles. His serum PSA level was 4.9 ng/ml and a six-core biopsy revealed the presence of a prostate adenocarcinoma with a Gleason score of 7 (3+4). He was treated with radical prostatectomy. Repeat PSA tests revealed a gradual rise in PSA levels despite androgen deprivation therapy with bicalutamide and goserelin over the course of 3 years. Genetic evaluation was undertaken in view of his personal and family history. The proband died at the age of 58 years of widespread metastasis.

Investigations. PSA testing, six-core biopsy, genetic counselling and mutation analysis for French Canadian founder mutations in the BRCA1 and BRCA2 genes, histopathological review of tumour tissue from family members, examination of loss of heterozygosity at the BRCA2 gene locus, immunohistochemistry to determine the expression of the ERG nuclear oncoprotein in prostate tumours, genotyping with eight selected risk-associated single nucleotide polymorphisms, Doppler ultrasonography of the leg, CT of the abdomen and pelvis with intravenous and oral contrast, chest CT with intravenous contrast for the assessment of metastatic prostate cancer, genetic testing for the G84E variant in the HOXB13 gene.

Diagnosis. Early-onset and aggressive prostate cancer associated with a nonsense French Canadian BRCA2 founder mutation, c.5857G>T (p.Glu1953*).

Management. Radical prostatectomy, hormone therapy with bicalutamide and goserelin, palliative chemotherapy initially with docetaxel plus prednisone then with mitoxantrone plus prednisone, as well as genetic counselling and testing for the proband and his family members.

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Figure 1: Pedigree analysis of a family affected by hereditary prostate cancer.
Figure 2: Histology of prostate tissue that harbours the familial BRCA2 mutation (from individual III-6).

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Acknowledgements

We are indebted to the proband and his family members for their contributions to this Case Study. The work was supported by funds provided by Drs Armen Aprikian and Franck Bladou, Division of Urology, McGill University, and by a subcontract to the NIH Grant # 5U01CA089600-09 [International Consortium on Prostate Cancer Genetics (ICPCG), PI: William Isaacs].

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Research Institute of McGill University Health Centre, Montreal, H3G 1A4, QC, Canada

    Nassim Taherian & Nancy Hamel

  2. Division of Anatomic Pathology, Hôpital du Sacré-Cœur de Montréal, Montreal, H4J 1C5, QC, Canada

    Louis R. Bégin

  3. Department of Pathology and Laboratory Medicine and Oncology, University of Calgary and Southern Alberta Cancer Institute, Calgary, T2V 1P9, AB, Canada

    Tarek A. Bismar

  4. Department of Dermatology, University of Utah School of Medicine, Salt Lake City, 84132, UT, USA

    David E. Goldgar & Bing-Jian Feng

  5. Department of Oncology and Human Genetics, Program in Cancer Genetics, McGill University, Montreal, H2W 1S6, QC, Canada

    William D. Foulkes

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Contributions

N. Taherian researched data for and wrote this article. All authors made a substantial contribution to discussion of content and review of the manuscript before submission.

Corresponding author

Correspondence to William D. Foulkes.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Liability classes (DOC 46 kb)

Supplementary Table 2

Total number of risk alleles and genotype score weighted by the logarithmic of the odds (LOD) ratio for 8 different SNPs (DOC 58 kb)

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Taherian, N., Hamel, N., Bégin, L. et al. Familial prostate cancer: the damage done and lessons learnt. Nat Rev Urol 10, 116–122 (2013). https://doi.org/10.1038/nrurol.2012.257

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