Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Prostate cancer incidence varies among males from different Y-chromosome lineages

Abstract

The incidence rate of prostate cancer in African-American males is two times higher than Caucasian men and ten times higher than Japanese men. The geographical specificity of Y haplogroups implies that males from different ethnic groups undoubtedly have various Y lineages with different Y-chromosomal characteristics that may affect their susceptibility or resistance to such a male-specific cancer. To confirm this hypothesis we studied the Y-chromosomal haplogroups of 92 Japanese prostate cancer patients comparing them with randomly selected 109 unrelated healthy Japanese male controls who were confirmed to be residents of the same geographical area. Males could be classified using three binary Y-chromosome markers (sex-determining region Y (SRY), YAP, 47z) into four haplogroups DE, O2b*, O2b1, and untagged group. Our results confirmed that prostate cancer incidence varies among males from different Y-chromosome lineages. Males from DE and the untagged haplogroups are at a significantly higher risk to develop prostate cancer than O2b* and O2b1 haplogroups (P=0.01), odds ratio 2.17 and 95% confidence interval (1.16–4.07). Males from haplogroup DE are over-represented in the patient group showing a percentage of 41.3%. The underlying possible causes of susceptibility variations of different Y lineages for such a male-specific cancer tumorigenesis are discussed. These findings explain the lower incidence of prostate cancer in Japanese and other South East Asian males than other populations. To our knowledge, this is the first reliable study examining the association between prostate cancer and Y-chromosomal haplogroups, comparing prostate cancer patients with carefully selected matched controls.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Greenlee RT, Hill-Harmon MB, Murray T, Thun M . Cancer statistics, 2001. CA Cancer J Clin 2001; 51: 15–36.

    Article  CAS  Google Scholar 

  2. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55: 10–30.

    Article  Google Scholar 

  3. Parkin DM, Pisani P, Ferlay J . Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999; 80: 827–841.

    Article  CAS  Google Scholar 

  4. Taylor JD, Holmes TM, Swanson GM . Descriptive epidemiology of prostate cancer in metropolitan Detroit. Cancer ( 1994; 73: 1704–1707.

    Article  CAS  Google Scholar 

  5. Oishi K, Yoshida O, Schroeder FH . The geography of prostate cancer and its treatment in Japan. Cancer Surv 1995; 23: 267–280.

    CAS  PubMed  Google Scholar 

  6. Sata F, Umemura T, Kishi R . The epidemiology of prostate cancer – recent trends in prostate cancer incidence and mortality. Gan To Kagaku Ryoho 2001; 28: 184–188.

    CAS  PubMed  Google Scholar 

  7. 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 

  8. Gronberg H . Prostate cancer epidemiology. Lancet 2003; 361: 859–864.

    Article  Google Scholar 

  9. Lundgren R, Mandahl N, Heim S, Limon J, Henrikson H, Mitelman F . Cytogenetic analysis of 57 primary prostatic adenocarcinomas. Genes Chromosomes Cancer 1992; 4: 16–24.

    Article  CAS  Google Scholar 

  10. Konig JJ, Teubel W, van Dongen JW, Romijin JC, Hagemeijer A, Schroder FH . Loss and gain of chromosomes 1, 18, and Y in prostate cancer. Prostate 1994; 25: 281–291.

    Article  CAS  Google Scholar 

  11. Alcaraz A, Takahashi S, Brown JA, Herath JF, Bergstralh EJ, Larson-Keller JJ et al. Aneuploidy and aneusomy of chromosome 7 detected by fluorescence in situ hybridization are markers of poor prognosis in prostate cancer. Cancer Res 1994; 54: 3998–4002.

    CAS  PubMed  Google Scholar 

  12. Brothman AR, Maxwell TM, Cui J, Deubler DA, Zhu XL . Chromosomal clues to the development of prostate tumors. Prostate 1999; 38: 303–312.

    Article  CAS  Google Scholar 

  13. Alers JC, Rochat J, Krijtenburg PJ, Hop WC, Kranse R, Rosenberg C et al. Identification of genetic markers for prostatic cancer progression. Lab Invest 2000; 80: 931–942.

    Article  CAS  Google Scholar 

  14. Suzuki K, Matsui H, Ohtake N, Nakata S, Takei T, Nakazato H et al. A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese. J Biomed Sci 2003; 10: 430–435.

    Article  CAS  Google Scholar 

  15. Van Dekken H, Alers J . Loss of chromosome Y in prostatic cancer cells but not in stromal tissue. Cancer Genet Cytogenet 1993; 66: 131–132.

    Article  CAS  Google Scholar 

  16. Alers JC, Krijtenburg PJ, Vissers CJ, Bosman FT, van der Kwast TH, Van Dekken H . Cytogenetic heterogeneity and histologic tumor growth patterns in prostatic cancer. Cytometry 1995; 21: 84–94.

    Article  CAS  Google Scholar 

  17. Lau YF, Zhang J . Expression analysis of thirty one Y chromosome genes in human prostate cancer. Mol Carcinog 2000; 27: 308–321.

    Article  CAS  Google Scholar 

  18. Kasahara K, Taguchi T, Yamasaki I, Karashima T, Kamada M, Yuri K et al. Fluorescence in situ hybridization to assess transitional changes of aneuploidy for chromosomes 7, 8, 10, 12, 16, X and Y in metastatic prostate cancer following anti-androgen therapy. Int J Oncol 2001; 19: 543–549.

    CAS  PubMed  Google Scholar 

  19. Karan D, Schmied BM, Dave BJ, Wittel UA, Lin MF, Batra SK . Decreased androgen-responsive growth of human prostate cancer is associated with increased genetic alterations. Clin Cancer Res 2001; 7: 3472–3480.

    CAS  PubMed  Google Scholar 

  20. Dasari VK, Deng D, Perinchery G, Yeh CC, Dahiya R . DNA methylation regulates the expression of Y chromosome specific genes in prostate cancer. J Urol 2002; 167: 335–338.

    Article  CAS  Google Scholar 

  21. Perinchery G, Sasaki M, Angan A, Kumar V, Carroll P, Dahiya R . Deletion of Y-chromosome specific genes in human prostate cancer. J Urol 2000; 163: 1339–1342.

    Article  CAS  Google Scholar 

  22. Dasari VK, Goharderakhshan RZ, Perinchery G, Li LC, Tanaka Y, Alonzo J et al. Expression analysis of Y chromosome genes in human prostate cancer. J Urol 2001; 165: 1335–1341.

    Article  CAS  Google Scholar 

  23. Jordan JJ, Hanlon AL, Al-Saleem TI, Greenberg RE, Tricoli JV . Loss of the short arm of the Y chromosome in human prostate carcinoma. Cancer Genet Cytogenet 2001; 124: 122–126.

    Article  CAS  Google Scholar 

  24. Jobling M, Tyler-Smith C . Father and sons – the Y chromosome and human evolution. Trends Genet 1995; 11: 449–456.

    Article  CAS  Google Scholar 

  25. Jobling MA, Tyler-Smith C . New uses for new haplotypes the human Y chromosome, disease and selection. Trends Genet 2000; 16: 356–362.

    Article  CAS  Google Scholar 

  26. Shinka T, Tomita K, Toda T, Kotliarova SE, Lee J, Kuroki Y et al. Genetic variations on the Y chromosome in the Japanese population and implications for modern human Y chromosome lineage. J Hum Genet 1999; 44: 240–245.

    Article  CAS  Google Scholar 

  27. Kuroki Y, Iwamoto T, Lee JW, Yoshike M, Nozawa S, Nishida T et al. Spermatogenic ability is different among males in different Y chromosome lineage. J Hum Genet 1999; 44: 289–292.

    Article  CAS  Google Scholar 

  28. Y Chromosome Consortium. A nomenclature system for the tree of human Y-chromosomal binary haplogroups. Genome Res 2002; 12: 339–348.

  29. The Japanese Urological Association and the Japanese Society of Pathology. General Rules for Clinical and Pathological Studies on Prostate Cancer, 2nd edn, Kanahara-Shuppan Co.: Tokyo, Japan, 1992.

  30. Gleason DF, the VACURG. Histological grading and clinical staging of prostatic carcinoma. In: Tannenbaum M (ed). Urologic Pathology. Lea & Febiger: Philadelphia, 1977, pp 171–197.

    Google Scholar 

  31. International Union Against Cancer. Urological tumours: prostate. In: Hermanek P, Sobin LH (eds). TNM Classification of Malignant Tumors, 4th edn, Springer-Verlag: Berlin, 1992, pp 141–144.

  32. Sambrook F, Fritsch EF, Maniathis T . Molecular Cloning: A Laboratoty Manual, 2nd edn, Cold Spring Harbor Laboratory Press: New York, 1989.

    Google Scholar 

  33. Hammer MF . A recent insertion of an Alu element on the Y chromosome is a useful marker for human population studies. Mol Biol Evol 1994; 11: 749–761.

    CAS  PubMed  Google Scholar 

  34. Hammer MF, Horai S . Y chromosomal DNA variation and the peopling of Japan. Am J Hum Genet 1995; 56: 951–962.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Nakahori Y . A hypothesis on the evolution of sex chromosomes. Front Endocrinol 1996; 17: 1–14.

    Google Scholar 

  36. De-Rosa M, De-Brasi D, Zarrilli S, Paesano L, Pivonello R, D'Agostino A et al. Short stature and azoospermia in a patient with Y chromosome long arm deletion. J Endocrinol Invest 1997; 20: 623–628.

    Article  CAS  Google Scholar 

  37. Vogt PH . Human Y chromosome deletions in Yq11 and male fertility. Adv Exp Med Biol 1997; 424: 17–30.

    Article  CAS  Google Scholar 

  38. Bourgeron T, Barbaux S, McElreavey K, Fellous M . Y chromosome and spermatogenesis. Contracept Fertil Sex 1997; 25: 620–625.

    CAS  PubMed  Google Scholar 

  39. Salo P, Ignatius J, Simola KO, Tahvanainen E, Kaariainen H . Clinical features of nine males with molecularly defined deletions of the Y chromosome long arm. J Med Genet 1995; 32: 711–715.

    Article  CAS  Google Scholar 

  40. Maxson SC . Searching for candidate genes with effects on an agonistic behavior, offense, in mice. Behav Genet 1996; 26: 471–476.

    Article  CAS  Google Scholar 

  41. Corballis MC, Lee K, McManus IC, Crow TJ . Location of the handedness gene on the X and Y chromosomes. Am J Med Genet 1996; 67: 50–52.

    Article  CAS  Google Scholar 

  42. Alvesalo L . Sex chromosomes and human growth. A dental approach. Hum Genet 1997; 101: 1–5.

    Article  CAS  Google Scholar 

  43. Crow TJ . Commentary on Annett, Yeo et al., Klar, Saugstad and Orr: cerebral asymmetry, language and psychosis–the case for a Homo sapiens-specific sex-linked gene for brain growth. Schizophr Res 1999; 39: 219–231.

    Article  CAS  Google Scholar 

  44. Kittles RA, Bergen AW, Urbanek M, Virkkunen M, Linnoila M, Goldman D et al. Autosomal, mitochondrial, and Y chromosome DNA variation in Finland: evidence for a male-specific bottleneck. Am J Phys Anthropol 1999; 108: 381–399.

    Article  CAS  Google Scholar 

  45. Ellis JA, Stebbing M, Harrap SB . Association of the human Y chromosome with high blood pressure in the general population. Hypertension 2000; 36: 731–733.

    Article  CAS  Google Scholar 

  46. Krausz C, Quintana-Murci L, Rajpert-De Meyts E, Jorgensen N, Jobling MA, Rosser ZH et al. Identification of a Y chromosome haplogroup associated with reduced sperm counts. Hum Mol Genet 2001; 10: 1873–1877.

    Article  CAS  Google Scholar 

  47. Ellis JA, Stebbing M, Harrap SB . Significant population variation in adult male height associated with the Y chromosome and the aromatase gene. J Clin Endocrinol Metab 2001; 86: 4147–4150.

    Article  CAS  Google Scholar 

  48. Ewis AA, Lee J, Naroda T, Sasahara K, Sano T, Kagawa S et al. Linkage between prostate cancer incidence and different alleles of the human Y-linked tetranucleotide polymorphism DYS19. J Med Invest 2002; 49: 56–60.

    PubMed  Google Scholar 

  49. Quintana-Murci L, Weale ME, Thomas MG, Erdei E, Bradman N, Shanks JH et al. Y chromosome haplotypes and testicular cancer in the English population. J Med Genet 2003; 40: e20.

    Article  CAS  Google Scholar 

  50. Whittemore AS, Wu AH, Kolonel LN, John EM, Gallagher RP, Howe GR et al. Family history and prostate cancer risk in black, white, and Asian men in the united states and Canada. Am J Epidemiol 1995; 141: 732–740.

    Article  CAS  Google Scholar 

  51. Tsuchiya K, Reijo R, Page DC, Disteche CM . Gonadoblastoma: molecular definition of the susceptibility region on the Y chromosome. Am J Hum Genet 1995; 57: 1400–1407.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Lau YF . Gonadoblastoma, testicular and prostate cancers, and the TSPY gene. Am J Hum Genet 1999; 64: 921–927.

    Article  CAS  Google Scholar 

  53. Schnieders F, Dork T, Arnemann J, Vogel T, Werner M, Schmidtke J . Testis-specific protein, Y-encoded (TSPY) expression in testicular tissues. Hum Mol Genet 1996; 5: 1801–1807.

    Article  CAS  Google Scholar 

  54. Oakey R, Tyler-Smith C . Y chromosome DNA haplotyping suggests that most European and Asian men are descended from one of two males. Genomics 1990; 7: 325–330.

    Article  CAS  Google Scholar 

  55. Catalona WJ . Management of cancer of the prostate. N Engl J Med 1994; 331: 996–1004.

    Article  CAS  Google Scholar 

  56. Suzuki H, Ueda T, Ichikawa T, Ito H . Androgen receptor involvement in the progression of prostate cancer. Endocr Relat Cancer 2003; 10: 209–216.

    Article  CAS  Google Scholar 

  57. Yuan X, Lu ML, Li T, Balk SP . SRY interacts with and negatively regulates androgen receptor transcriptional activity. J Biol Chem 2001; 276: 46647–46654.

    Article  CAS  Google Scholar 

  58. Hemminki K, Dong C, Vaittinen P . Cancer risks to spouses and offspring in the Family-Cancer Database. Genet Epidemiol 2001; 20: 247–257.

    Article  CAS  Google Scholar 

  59. Kushi L, Giovannucci E . Dietary fat and cancer. Am J Med 2002; 113 (Suppl 9B): 63S–70S.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank all the physicians, urologists and pathologists of different university and municipal hospitals in Shikoku Island for providing samples and clinical information. Also, many thanks are due to Miss Tsuji K., Unemi Y and Endo A for their excellent technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A A Ewis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ewis, A., Lee, J., Naroda, T. et al. Prostate cancer incidence varies among males from different Y-chromosome lineages. Prostate Cancer Prostatic Dis 9, 303–309 (2006). https://doi.org/10.1038/sj.pcan.4500876

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.pcan.4500876

Keywords

This article is cited by

Search

Quick links