Familial Cancer

, Volume 8, Issue 2, pp 167–171 | Cite as

Concordant colon tumors in monozygotic twins previously treated for prostate cancer

  • Arnoud Templeton
  • Giancarlo Marra
  • Emanuele Valtorta
  • Karl Heinimann
  • Hansjakob Müller
  • Dieter Köberle
  • Silke Gillessen


This report describes the quasi-simultaneous occurrence of colon cancers in monozygotic twin brothers (age 63 years) who had undergone androgen deprivation therapy for prostate cancers 4 years earlier. Concordance among male twins for both of these cancers has never been reported. Although the family history suggested possible genetic predispositions to both cancers, the twins have no evidence of the genetic alterations associated with hereditary colorectal tumors. We explore the possibility that colorectal tumorigenesis in these twins was fuelled by a combination of genetic and iatrogenic factors, in particular the androgen deprivation therapy used to treat their prostate cancers.


Androgen deprivation Colon cancer Monozygotic twins Prostate cancer Wnt signalling 



We are very grateful to the members of the family described in this report, who graciously provided permission for publication of this information for the medical community; to Paul Lichtenstein for his excellent input and for the information he provided regarding the Swedish Twin Registry; to Henry T. Lynch, Sapna Syngal, and Fred Li for productive discussion of the cases; and to Marian Kent for editorial assistance. This work was supported in part by the Sassella Stiftung Zurich and Central Switzerland Cancer League grants to GM. Genetic analyses were supported by an Oncosuisse grant to KH.


  1. 1.
    Lichtenstein P, Holm NV, Verkasalo PK et al (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85. doi: 10.1056/NEJM200007133430201 PubMedCrossRefGoogle Scholar
  2. 2.
    Schaid DJ (2004) The complex genetic epidemiology of prostate cancer. Hum Mol Genet 13(Spec No 1):R103–R121PubMedCrossRefGoogle Scholar
  3. 3.
    Vasen HF (2000) Clinical diagnosis and management of hereditary colorectal cancer syndromes. J Clin Oncol 18:81S–92SPubMedGoogle Scholar
  4. 4.
    Edwards SM, Eeles RA (2004) Unravelling the genetics of prostate cancer. Am J Med Genet C Semin Med Genet 129:65–73. doi: 10.1002/ajmg.c.30027 CrossRefGoogle Scholar
  5. 5.
    Steinberg GD, Carter BS, Beaty TH et al (1990) Family history and the risk of prostate cancer. Prostate 17:337–347. doi: 10.1002/pros.2990170409 PubMedCrossRefGoogle Scholar
  6. 6.
    Johns LE, Houlston RS (2003) A systematic review and meta-analysis of familial prostate cancer risk. BJU Int 91:789–794. doi: 10.1046/j.1464-410X.2003.04232.x PubMedCrossRefGoogle Scholar
  7. 7.
    Gronberg H, Damber L, Damber JE (1994) Studies of genetic factors in prostate cancer in a twin population. J Urol 152:1484–1487PubMedGoogle Scholar
  8. 8.
    Page WF, Braun MM, Partin AW et al (1997) Heredity and prostate cancer: a study of World War II veteran twins. Prostate 33:240–245. doi:10.1002/(SICI)1097-0045(19971201)33:4<240::AID-PROS3>3.0.CO;2-LPubMedCrossRefGoogle Scholar
  9. 9.
    Cybulski C, Gorski B, Huzarski T et al (2004) CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet 75:1131–1135. doi: 10.1086/426403 PubMedCrossRefGoogle Scholar
  10. 10.
    Lichtenstein P, Sullivan PF, Cnattingius S et al (2006) The Swedish Twin registry in the third millennium: an update. Twin Res Hum Genet 9:875–882. doi: 10.1375/twin.9.6.875 PubMedCrossRefGoogle Scholar
  11. 11.
    Nelson WG, De Marzo AM, Isaacs WB (2003) Prostate cancer. N Engl J Med 349:366–381. doi: 10.1056/NEJMra021562 PubMedCrossRefGoogle Scholar
  12. 12.
    Gelmann EP (2008) Complexities of prostate-cancer risk. N Engl J Med 358:961–963. doi: 10.1056/NEJMe0708703 PubMedCrossRefGoogle Scholar
  13. 13.
    Truninger K, Menigatti M, Luz J et al (2005) Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Gastroenterology 128:1160–1171. doi: 10.1053/j.gastro.2005.01.056 PubMedCrossRefGoogle Scholar
  14. 14.
    Catalano MG, Pfeffer U, Raineri M et al (2000) Altered expression of androgen-receptor isoforms in human colon-cancer tissues. Int J Cancer 86:325–330. doi:10.1002/(SICI)1097-0215(20000501)86:3<325::AID-IJC4>3.0.CO;2-GPubMedCrossRefGoogle Scholar
  15. 15.
    Pereira MA, Khoury MD (1991) Prevention by chemopreventive agents of azoxymethane-induced foci of aberrant crypts in rat colon. Cancer Lett 61:27–33. doi: 10.1016/0304-3835(91)90073-Q PubMedCrossRefGoogle Scholar
  16. 16.
    Rao CV, Tokumo K, Rigotty J et al (1991) Chemoprevention of colon carcinogenesis by dietary administration of piroxicam, alpha-difluoromethylornithine, 16 alpha-fluoro-5-androsten-17-one, and ellagic acid individually and in combination. Cancer Res 51:4528–4534PubMedGoogle Scholar
  17. 17.
    Stebbings WS, Vinson GP, Farthing MJ et al (1989) Effect of steroid hormones on human colorectal adenocarcinoma xenografts, of known steroid-receptor status, in nude mice. J Cancer Res Clin Oncol 115:439–444. doi: 10.1007/BF00393333 PubMedCrossRefGoogle Scholar
  18. 18.
    Aoki K, Nakajima A, Mukasa K et al (2003) Prevention of diabetes, hepatic injury, and colon cancer with dehydroepiandrosterone. J Steroid Biochem Mol Biol 85:469–472. doi: 10.1016/S0960-0760(03)00219-X PubMedCrossRefGoogle Scholar
  19. 19.
    Izbicki JR, Hamilton SR, Wambach G et al (1990) Effects of androgen manipulations on chemically induced colonic tumours and on macroscopically normal colonic mucosa in male Sprague-Dawley rats. Br J Cancer 61:235–240PubMedGoogle Scholar
  20. 20.
    Chesire DR, Isaacs WB (2002) Ligand-dependent inhibition of beta-catenin/TCF signaling by androgen receptor. Oncogene 21:8453–8469. doi: 10.1038/sj.onc.1206049 PubMedCrossRefGoogle Scholar
  21. 21.
    Mulholland DJ, Read JT, Rennie PS et al (2003) Functional localization and competition between the androgen receptor and T-cell factor for nuclear beta-catenin: a means for inhibition of the Tcf signaling axis. Oncogene 22:5602–5613. doi: 10.1038/sj.onc.1206802 PubMedCrossRefGoogle Scholar
  22. 22.
    Chen SY, Wulf G, Zhou XZ et al (2006) Activation of beta-catenin signaling in prostate cancer by peptidyl-prolyl isomerase Pin1-mediated abrogation of the androgen receptor-beta-catenin interaction. Mol Cell Biol 26:929–939. doi: 10.1128/MCB.26.3.929-939.2006 PubMedCrossRefGoogle Scholar
  23. 23.
    Van der Flier LG, Sabates-Bellver J, Oving I et al (2007) The intestinal Wnt/TCF signature. Gastroenterology 132:628–632. doi: 10.1053/j.gastro.2006.08.039 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Arnoud Templeton
    • 1
  • Giancarlo Marra
    • 2
  • Emanuele Valtorta
    • 2
  • Karl Heinimann
    • 3
  • Hansjakob Müller
    • 3
  • Dieter Köberle
    • 1
  • Silke Gillessen
    • 1
  1. 1.Department of Medical OncologyKantonsspitalSt. GallenSwitzerland
  2. 2.Institute of Molecular Cancer ResearchUniversity of ZurichZurichSwitzerland
  3. 3.Division of Medical Genetics UKBB/DKBWUniversity of BaselBaselSwitzerland

Personalised recommendations