Skip to main content
SpringerLink
Log in

The Genetics of Testicular Germ Cell Tumours

  • Conference paper
Germ Cell Tumours V

Abstract

Testicular Germ Cell Tumours (TGCT) affect 1 in 400 men in the UK. Two per cent of TGCT cases report another affected family member. The familial relative risk is estimated to be 8–10 fold for brothers of cases and 4–6 fold for fathers and sons. This familial relative risk is considerably higher than for most common cancers suggesting that the contribution of genetic factors to TGCT may be relatively more important than for other cancers. However, the search by genetic linkage analysis for familial TGCT susceptibility genes has been confounded by the limited number of large multiple case families. The International Testicular Cancer Linkage Consortium family set currently consists of more than 190 families with at least two cases of TGCT. A genome-wide search conducted on 100 families has yielded strong evidence for a TGCT susceptibility gene on the X chromosome. This gene appears to predispose to bilateral TGCT and also possibly to undescended testis. This is the first familial TGCT gene to be localised and the first cancer susceptibility gene mapped in a genome wide search using predominantly sib pairs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ferlay, J, Bray P, Pisani P, and Parkin DM GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.IARC CancerBase No.5. Lyon. 2001. IARCPress.

    Google Scholar 

  2. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int. J.Cancer 1999;80:827–41.

    Article  PubMed  CAS  Google Scholar 

  3. Power DA, Brown RS, Brock CS, Payne HA, Majeed A, Babb P. Trends in testicular carcinoma in England and Wales, 1971–99. BJU.Int. 2001;87:361–5.

    Article  PubMed  CAS  Google Scholar 

  4. Bergstrom R, Adami HO, Mohner M et al. Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon. J.Natl. Cancer Inst. 1996;88:727–33.

    Article  PubMed  CAS  Google Scholar 

  5. Skakkebaek NE. Possible carcinoma-in-situ of the testis. Lancet 1972;2:516–7.

    Article  PubMed  CAS  Google Scholar 

  6. Jorgensen N, Rajpert-De Meyts E, Graem N, Muller J, Giwercman A, Skakkebaek NE. Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells. Lab Invest 1995;72:223–31.

    PubMed  CAS  Google Scholar 

  7. Giwercman A, Muller J, Skakkebaek NE. Prevalence of carcinoma in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly. J.Urol. 1991;145:77–80.

    PubMed  CAS  Google Scholar 

  8. Forman D, Oliver RT, Brett AR et al. Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis. Br.J Cancer 1992;65:255–62.

    Article  PubMed  CAS  Google Scholar 

  9. UK Testicular Cancer Study Group. Aetiology of testicular cancer: association with congenital abnormalities, age at puberty, infertility, and exercise. United Kingdom Testicular Cancer Study Group [see comments]. BMJ. 1994;308:1393–9.

    Article  Google Scholar 

  10. Osterlind A, Berthelsen JG, Abildgaard N et al. Risk of bilateral testicular germ cell cancer in Denmark: 1960–1984. J.Natl.Cancer Inst. 1991;83:1391–5.

    Article  PubMed  CAS  Google Scholar 

  11. Wanderas EH, Fossa SD, Tretli S. Risk of a second germ cell cancer after treatment of a primary germ cell cancer in 2201 Norwegian male patients. Eur.J.Cancer 1997;33:244–52.

    Article  PubMed  CAS  Google Scholar 

  12. von der MH, Rorth M, Walbom-Jorgensen S et al. Carcinoma in situ of contralateral testis in patients with testicular germ cell cancer: study of 27 cases in 500 patients. Br.Med.J.(Clin.Res.Ed) 1986;293:1398–401.

    Article  Google Scholar 

  13. Dieckmann KP. Loy V. Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms. J.Clin.Oncol. 1996;14:3126–32.

    PubMed  CAS  Google Scholar 

  14. Loy V. Dieckmann KP. Prevalence of contralateral testicular intraepithelial neoplasia (carcinoma in situ) in patients with testicular germ cell tumour. Results of the German multicentre study. Eur. Urol. 1993;23:120–2.

    PubMed  CAS  Google Scholar 

  15. Brown LM, Pottern LM, Hoover RN. Testicular cancer in young men: the search for causes of the epidemic increase in the United States. J.Epidemiol Community.Health 1987;41:349–54.

    Article  PubMed  CAS  Google Scholar 

  16. Swerdlow AJ, Huttly SR, Smith PG. Testicular cancer and antecedent diseases. Br.J Cancer 1987;55:97–103.

    Article  PubMed  CAS  Google Scholar 

  17. Swerdlow A.J. Prenatal and familiar associations of testicular cancer. Huttly S.R.A., Smith P. G. Britih Journal of Cancer 55, 571–577.1987. Ref Type: Generic

    CAS  Google Scholar 

  18. Swerdlow AJ, Higgins CD, Pike MC. Risk of testicular cancer in cohort of boys with cryptorchidism. BMJ 1997;314:150711.

    Article  Google Scholar 

  19. Moller H, Skakkebaek NE. Risk of testicular cancer in subfertile men: case-control study. BMJ 1999;318:559–62.

    Article  PubMed  CAS  Google Scholar 

  20. Jacobsen R, Bostofte E, Engholm G et al. Risk of testicular cancer in men with abnormal semen characteristics: cohort study. BMJ 2000;321:789–92.

    Article  PubMed  CAS  Google Scholar 

  21. Harland SJ, Cook PA, Fossa SD et al. Intratubular germ cell neoplasia of the contralateral testis in testicular cancer: defining a high risk group. J.Urol. 1998;160:1353–7.

    Article  PubMed  CAS  Google Scholar 

  22. Prener A, Engholm G, Jensen OM. Genital anomalies and risk for testicular cancer in Danish men. Epidemiology 1996;7:14–9.

    Article  PubMed  CAS  Google Scholar 

  23. Tollerud DJ, Blattner WA, Fraser MC et al Familial testicular cancer and urogenital developmental anomalies. Cancer 1985;55:1849–54.

    Article  PubMed  CAS  Google Scholar 

  24. Karagas MR, Weiss NS, Strader CH, Daling JR. Elevated intrascrotal temperature and the incidence of testicular cancer in noncryptorchid men. Am.J.Epidemiol. 1989;129:1104–9.

    PubMed  CAS  Google Scholar 

  25. Verp MS,.Simpson JL. Abnormal sexual differentiation and neoplasia.

    Google Scholar 

  26. Collins GM, Kim DU, Logrono R, Rickert RR, Zablow A, Breen JL. Pure seminoma arising in androgen insensitivity syndrome (testicular feminization syndrome): a case report and review of the literature. Mod.Pathol. 1993;6:89–93.

    PubMed  CAS  Google Scholar 

  27. Hasle H, Mellemgaard A, Nielsen J, Hansen J. Cancer incidence in men with Klinefelter syndrome. Br. J.Cancer 1995;71:416–20.

    Article  PubMed  CAS  Google Scholar 

  28. Hasle H, Jacobsen BB, Asschenfeldt P, Andersen K. Mediastinal germ cell tumour associated with Klinefelter syndrome. A report of case and review of the literature. Eur.J.Pediatr. 1992;151:735–9.

    Article  PubMed  CAS  Google Scholar 

  29. Okada H, Fujioka H, Tatsumi N et al Klinefelter’s syndrome in the male infertility clinic. Hum.Reprod. 1999;14:946–52.

    Article  PubMed  CAS  Google Scholar 

  30. Reddy SR, Svec F, Richardson P. Seminoma of the testis in a patient with 48, XXYY variant of Klinefelter’s syndrome. South.Med.J. 1991;84:773–5.

    Article  PubMed  CAS  Google Scholar 

  31. Carroll PR, Morse MJ, Koduru PP, Chaganti RS. Testicular germ cell tumor in patient with Klinefelter syndrome. Urology. 1988;31:72–4.

    Article  PubMed  CAS  Google Scholar 

  32. Muller J, Skakkebaek NE, Ratcliffe SG. Quantified testicular histology in boys with sex chromosome abnormalities. Int.J.Androl 1995;18:57–62.

    Article  PubMed  CAS  Google Scholar 

  33. Satge D, Sommelet D, Geneix A, Nishi M, Malet P, Vekemans M. A tumor profile in Down syndrome. Am.J.Med.Genet. 1998;78:207–16.

    Article  PubMed  CAS  Google Scholar 

  34. Satge D, Sasco AJ, Cure H, Leduc B, Sommelet D, Vekemans MJ. An excess of testicular germ cell tumors in Down’s syndrome: three case reports and a review of the literature. Cancer 1997;80:929–35.

    Article  PubMed  CAS  Google Scholar 

  35. Dieckmann KP, Rube C, Henke RP. Association of Down’s syndrome and testicular cancer. J Urol. 1997;157:1701–4.

    Article  PubMed  CAS  Google Scholar 

  36. Heimdal K, Olsson H, Tretli S, Flodgren P, Borresen AL, Fossa SD. Familial testicular cancer in Norway and southern Sweden. Br.J.Cancer 1996;73:964–9.

    Article  PubMed  CAS  Google Scholar 

  37. Wilkinson TJ, Colls BM, Schluter PJ. Increased incidence of germ cell testicular cancer in New Zealand Maoris. Br.J.Cancer 1992;65:769–71.

    Article  PubMed  CAS  Google Scholar 

  38. Nicholson PW, Harland SJ. Inheritance and testicular cancer. Br.J.Cancer 1995;71:421–6.

    Article  PubMed  CAS  Google Scholar 

  39. Heimdal K, Olsson H, Tretli S, Fossa SD, Borresen AL, Bishop DT. A segregation analysis of testicular cancer based on Norwegian and Swedish families. Br.J.Cancer 1997;75:1084–7.

    Article  PubMed  CAS  Google Scholar 

  40. Knudson AG, Jr. Mutation and cancer: statistical study of retinoblastoma. Proc.Natl.Acad.Sci.U.S.A 1971;68:820–3.

    Article  PubMed  Google Scholar 

  41. Goss PE, Bulbul MA. Familial testicular cancer in five members of a cancer-prone kindred. Cancer 1990;66:2044–6.

    Article  PubMed  CAS  Google Scholar 

  42. Gedde-Dahl TJ, Hannisdal E, Klepp OH et al Testicular neoplasms occurring in four brothers. A search for a genetic predisposition. Cancer 1985;55:2005–9.

    Article  PubMed  Google Scholar 

  43. Rapley EA, Crockford GP, Teare D et al. Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours. Nat.Genet 2000.Feb.;24.(2.):197–200. 2000;24:197–200.

    CAS  Google Scholar 

  44. Raghavan D, Jelihovsky T, Fox RM. Father-son testicular malignancy. Does genetic anticipation occur? Cancer 1980;45:1005–9.

    Article  PubMed  CAS  Google Scholar 

  45. Han S, Peschel RE. Father-son testicular tumors: evidence for genetic anticipation? A case report and review of the literature. Cancer 2000;88:2319–25.

    Article  PubMed  CAS  Google Scholar 

  46. Lander E,.Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat.Genet. 1995;11:241–7.

    Article  PubMed  CAS  Google Scholar 

  47. Redolfi E, Montagna C, Mumm S et al Identification of CXorfl, a novel intronless gene in Xq27.3, expressed in human hippocampus. DNA Cell Biol. 1998;17:1009–16.

    Article  PubMed  CAS  Google Scholar 

  48. Phelan MC, Stevenson RE, Collins JL, Trent HE. Fragile X syndrome and neoplasia. Am.J.Med.Genet. 1988;30:77–82.

    Article  PubMed  CAS  Google Scholar 

  49. Leahy MG, Tonks S, Moses JH et al. Candidate regions for a testicular cancer susceptibility gene. Hum.MolGenet. 1995;4:1551–5.

    CAS  Google Scholar 

  50. Candidate regions for testicular cancer susceptibility genes. The International Testicular Cancer Linkage Consortium. APMIS 1998;106:64–70.

    Article  Google Scholar 

  51. Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES. Parametric and nonparametric linkage analysis: a unified multipoint approach. AmJ.Hum.Genet. 1996;58:1347–63.

    CAS  Google Scholar 

  52. Broman KW, Murray JC, Sheffield VC, White RL, Weber JL. Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet 1998;63:861–9.

    Article  PubMed  CAS  Google Scholar 

  53. Morton NE, Collins A, Lawerence S, Shields DC. Algorithms for a location database. Ann Hum Gene 1992;56:223–32.

    Article  CAS  Google Scholar 

  54. Xu J, Meyers D, Freije D et al. Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat. Genet. 1998;20:175–9.

    Article  PubMed  CAS  Google Scholar 

  55. Wooster R, Mangion J, Eeles R et al. A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome. Nat.Genet. 1992;2:132–4.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sections of Cancer Genetics, Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, SM2 5NG, UK

    E. A. Rapley & M. R. Stratton

  2. Imperial Cancer Research Fund Genetic Epidemiology Lab, Ashley Wing, Leeds, LS97TF, UK

    G. P. Crockford & D. T. Bishop

  3. CRC Genetic Epidemiology Unit, Strangeways Research Laboratories, Worts Causeway, Cambridge, CB1 8RN, UK

    D. F. Easton

Authors
  1. E. A. Rapley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. P. Crockford
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. F. Easton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. R. Stratton
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. T. Bishop
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. ICRF Cancer Medicine Research Unit, St James’s University Hospital, Leeds, UK

    Patricia Harnden MD, PhD, FRCPath, MBA

  2. Huddersfield Royal Infirmary, Huddersfield, UK

    Johnathan K. Joffe MB BS, MD, FRCP

  3. Yorkshire Centre for Cancer Treatments, Cookridge Hospital, Leeds, UK

    William G. Jones MB CHB, FRCR, DMRT

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag London Limited

About this paper

Cite this paper

Rapley, E.A., Crockford, G.P., Easton, D.F., Stratton, M.R., Bishop, D.T. (2002). The Genetics of Testicular Germ Cell Tumours. In: Harnden, P., Joffe, J.K., Jones, W.G. (eds) Germ Cell Tumours V. Springer, London. https://doi.org/10.1007/978-1-4471-3281-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-3281-3_1

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-3283-7

  • Online ISBN: 978-1-4471-3281-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation