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Germline mutations in fumarate hydratase (FH) do not predispose to prostate cancer

Prostate Cancer and Prostatic Diseases volume 6, pages 12–14 (2003)Cite this article

Abstract

Inherited susceptibility to prostate cancer has been linked to a number of chromosomal regions, however no genes have been unequivocally shown to underlie reported linkages. The putative gene localised to chromosome 1q42–q43, has been designated PCaP. We have recently shown that germline mutations in the fumarate hydratase (FH) gene located on 1q43 cause smooth muscle tumours and renal cell carcinoma. It is conceivable that germline FH mutations might confer an increased risk of prostate cancer and underlie linkage of prostate cancer to PCaP. To examine this proposition we have analysed the entire coding region of FH in 160 prostate cancer cases in 77 multiple case families. No pathogenic mutations in FH were identified in any of the cases. This data makes it highly unlikely that mutations in FH confer susceptibility to prostate cancer.

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References

  1. Majeed A, Babb P, Jones J, Quinn M . Trends in prostate cancer incidence, mortality and survival in England and Wales 1971–1998. BJU Int 2000; 85: 1058–1062.

    Article  CAS  Google Scholar 

  2. Schulman CC, Zlotta AR, Denis L, Schroder FH, Sakr WA . Prevention of prostate cancer. Scand J Urol Nephrol 2000; 205 (Suppl): 50–61.

    Article  Google Scholar 

  3. Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC . Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci USA 1992; 89: 3367–3371.

    Article  CAS  Google Scholar 

  4. Peto J, Houlston RS . Genetics and the common cancers. Eur J Cancer 2001; 37 (Suppl 8): S88–S96.

    Article  CAS  Google Scholar 

  5. Gronberg H, Damber L, Damber J, Iselius L . Segregation analysis of prostate cancer in Sweden: support for dominant inheritance. Am J Epidemo 1997; 146: 552–557.

    Article  CAS  Google Scholar 

  6. Schaid DJ, McDonnell SK, Blute ML, Thibodeau SN . Evidence for autosomal dominant inheritance of prostate cancer. Am J Hum Genet 1998; 62: 1425–1438.

    Article  CAS  Google Scholar 

  7. Cui J, Staples MP, Hopper JL, English DR, McCredie MR, Giles GG . Segregation analyses of 1476 population-based Australian families affected by prostate cancer. Am J Hum Genet 2001; 68: 1207–1218.

    Article  CAS  Google Scholar 

  8. Smith JR, et al. Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search. Science 1996; 274: 1371–1374.

    Article  CAS  Google Scholar 

  9. Valeri E, et al. Genetic analysis of familial prostatic cancer: localisation of a gene predisposing to prostate cancer (PcaP) on chromosome 1q42.2–43. Prog Urol 1999; 9: 680–688.

    CAS  PubMed  Google Scholar 

  10. Xu J, et al. Evidence for a prostate cancer susceptibility locus on the X chromosome. Nature Genet 1998; 20: 175–179.

    Article  CAS  Google Scholar 

  11. Gibbs M, et al. Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. Am J Hum Genet 1999; 64: 776–787.

    Article  CAS  Google Scholar 

  12. Bock CH, et al. Analysis of the prostate cancer-susceptibility locus HPC20 in 172 families affected by prostate cancer. Am J Hum Genet 2001; 68: 795–801.

    Article  CAS  Google Scholar 

  13. Tavtigian SV, et al. A candidate prostate cancer susceptibility gene at chromosome 17p. Nature Genet 2001; 27: 172–180.

    Article  CAS  Google Scholar 

  14. Eagle LR, Yin X, Brothman AR, Williams BJ, Atkin NB, Prochownik EV . Mutation of the MXI1 gene in prostate cancer. Nature Genetics 2002; 30: 406–410.

    Article  Google Scholar 

  15. Cancel-Tassin G, Latil A, Valeri A, Mangin P, Fournier G, Berthon P, Cussenot O . PCAP is the major known prostate cancer predisposing locus in families from south and west Europe. Eur J Hum Genet 2001; 9: 135–142.

    Article  CAS  Google Scholar 

  16. Tomlinson A, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nature Genet 2002; 30: 406–410.

    Article  CAS  Google Scholar 

  17. Ganguly A, Rock M, Prockop D . Conformation sensitive gel electrophoresis for rapid detection of single-base differences in double stranded PCR products and DNA fragments: evidence for solvent induced bends in DNA heteroduplexes. Proc Natl Acad Sci USA 1993; 90: 10325–10329.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the families for their participation. This work was supported by the Prostate Cancer Charitable Trust, Prostate Research Campaign UK, The Times Christmas Appeal, Institute of Cancer Research, Cancer Research UK, formerly The Cancer Research Campaign UK (Grants SP2304/0201 and SP2304/0301) and a legacy from the estate of Marion Silcock. DNA sequencing was conducted in the Jean Rook Gene Cloning Laboratory, supported by BREAKTHROUGH Breast Cancer.

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  1. R S Houlston and R Eeles: Denotes equal senior authorship

Authors and Affiliations

  1. Molecular and Population Genetics Team, Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey, UK

    S Bevan & R S Houlston

  2. Translational Cancer Genetics Team, Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK

    S M Edwards, A Ardern Jones, A Dowe, C Southgate & R Eeles

  3. Academic Urology Unit, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey, UK

    D Dearnaley

  4. CRC Genetic Epidemiology Unit, Strangeways Research Labs, Worts Causeway, Cambridge, UK

    D F Easton

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  1. S Bevan
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The CRC/BPG UK Familial Prostate Cancer Study Collaborators,

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Correspondence to R S Houlston.

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Bevan, S., Edwards, S., Ardern Jones, A. et al. Germline mutations in fumarate hydratase (FH) do not predispose to prostate cancer. Prostate Cancer Prostatic Dis 6, 12–14 (2003). https://doi.org/10.1038/sj.pcan.4500616

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  • DOI: https://doi.org/10.1038/sj.pcan.4500616

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