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The link between benign prostatic hyperplasia and prostate cancer

Nature Reviews Urology volume 10, pages 49–54 (2013)Cite this article

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Abstract

Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common diseases of the prostate gland and represent significant burdens for patients and health-care systems in many countries. The two diseases share traits such as hormone-dependent growth and response to antiandrogen therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH as a causal factor for prostate cancer development could improve the accuracy of prognostication and expedite intervention, potentially reducing the number of men who die from prostate cancer.

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Figure 1: Shared risk factors such as inflammation, metabolic factors, hormonal influences, and genetic variation predispose men to both benign prostatic hyperplasia (BPH) and prostate cancer (depicted by black arrows).

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References

  1. Sommers, S. C. Endocrine changes with prostatic carcinoma. Cancer 10, 345–358 (1957).

    Article  CAS  PubMed  Google Scholar 

  2. Orsted, D. D., Bojesen, S. E., Nielsen, S. F. & Nordestgaard, B. G. Association of clinical benign prostate hyperplasia with prostate cancer incidence and mortality revisited: a nationwide cohort study of 3,009,258 men. Eur. Urol. 60, 691–698 (2011).

    Article  PubMed  Google Scholar 

  3. Ferlay, J. et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 127, 2893–2917 (2010).

    Article  CAS  PubMed  Google Scholar 

  4. Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2012. CA Cancer J. Clin. 62, 10–29 (2012).

    Article  PubMed  Google Scholar 

  5. McVary, K. T. BPH: epidemiology and comorbidities. Am. J. Manag. Care 12, S122–S128 (2006).

    PubMed  Google Scholar 

  6. Roehrborn, C. G. & Black, L. K. The economic burden of prostate cancer. BJU Int. 108, 806–813 (2011).

    Article  PubMed  Google Scholar 

  7. Lepor, H. Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. Rev. Urol. 6 (Suppl. 9), S3–S10 (2004).

    PubMed  PubMed Central  Google Scholar 

  8. Alcaraz, A., Hammerer, P., Tubaro, A., Schroder, F. H. & Castro, R. Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review. Eur. Urol. 55, 864–873 (2009).

    Article  PubMed  Google Scholar 

  9. Guess, H. A. Benign prostatic hyperplasia and prostate cancer. Epidemiol. Rev. 23, 152–158 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Nickel, J. C. et al. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur. Urol. 54, 1379–1384 (2008).

    Article  PubMed  Google Scholar 

  11. Montironi, R., Mazzucchelli, R., Lopez-Beltran, A., Scarpelli, M. & Cheng, L. Prostatic intraepithelial neoplasia: its morphological and molecular diagnosis and clinical significance. BJU Int. 108, 1394–1401 (2011).

    Article  PubMed  Google Scholar 

  12. Davidsson, S. et al. Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer. Cancer Epidemiol. Biomarkers Prev. 20, 2280–2287 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Merrimen, J. L. et al. Multifocal high grade prostatic intraepithelial neoplasia is a significant risk factor for prostatic adenocarcinoma. J. Urol. 182, 485–490 (2009).

    Article  PubMed  Google Scholar 

  14. De Marzo, A. M., Nelson, W. G., Bieberich, C. J. & Yegnasubramanian, S. Prostate cancer: new answers prompt new questions regarding cell of origin. Nat. Rev. Urol. 7, 650–652 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Andriole, G. L. et al. Effect of dutasteride on the risk of prostate cancer. N. Engl. J. Med. 362, 1192–1202 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Thompson, I. M. et al. The influence of finasteride on the development of prostate cancer. N. Engl. J. Med. 349, 215–224 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. De Nunzio, C. et al. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur. Urol. 60, 106–117 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. De Nunzio, C., Aronson, W., Freedland, S. J., Giovannucci, E. & Parsons, J. K. The correlation between metabolic syndrome and prostatic diseases. Eur. Urol. 61, 560–570 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. Chokkalingam, A. P. et al. Prostate carcinoma risk subsequent to diagnosis of benign prostatic hyperplasia: a population-based cohort study in Sweden. Cancer 98, 1727–1734 (2003).

    Article  PubMed  Google Scholar 

  20. Bostwick, D. G. et al. The association of benign prostatic hyperplasia and cancer of the prostate. Cancer 70, 291–301 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Armenian, H. K., Lilienfeld, A. M., Diamond, E. L. & Bross, I. D. Relation between benign prostatic hyperplasia and cancer of the prostate. A prospective and retrospective study. Lancet 2, 115–117 (1974).

    Article  CAS  PubMed  Google Scholar 

  22. Greenwald, P., Kirmss, V., Polan, A. K. & Dick, V. S. Cancer of the prostate among men with benign prostatic hyperplasia. J. Natl Cancer Inst. 53, 335–340 (1974).

    Article  CAS  PubMed  Google Scholar 

  23. Simons, B. D., Morrison, A. S., Young, R. H. & Verhoek-Oftedahl, W. The relation of surgery for prostatic hypertrophy to carcinoma of the prostate. Am. J. Epidemiol. 138, 294–300 (1993).

    Article  CAS  PubMed  Google Scholar 

  24. Schenk, J. M. et al. Association of symptomatic benign prostatic hyperplasia and prostate cancer: results from the prostate cancer prevention trial. Am. J. Epidemiol. 173, 1419–1428 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Thompson, I. M., Coltman, C. A. Jr & Crowley, J. Chemoprevention of prostate cancer: the Prostate Cancer Prevention Trial. Prostate 33, 217–221 (1997).

    Article  CAS  PubMed  Google Scholar 

  26. Jacobsen, S. J. et al. Do prostate size and urinary flow rates predict health care-seeking behavior for urinary symptoms in men? Urology 45, 64–69 (1995).

    Article  CAS  PubMed  Google Scholar 

  27. Meigs, J. B. et al. High rates of prostate-specific antigen testing in men with evidence of benign prostatic hyperplasia. Am. J. Med. 104, 517–525 (1998).

    Article  CAS  PubMed  Google Scholar 

  28. Allin, K. H., Bojesen, S. E. & Nordestgaard, B. G. Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J. Clin. Oncol. 27, 2217–2224 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Zacho, J. et al. Genetically elevated C-reactive protein and ischemic vascular disease. N. Engl. J. Med. 359, 1897–1908 (2008).

    Article  CAS  PubMed  Google Scholar 

  30. De Marzo, A. M., Nakai, Y. & Nelson, W. G. Inflammation, atrophy, and prostate carcinogenesis. Urol. Oncol. 25, 398–400 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. MacLennan, G. T. et al. The influence of chronic inflammation in prostatic carcinogenesis: a 5-year followup study. J. Urol. 176, 1012–1016 (2006).

    Article  PubMed  Google Scholar 

  32. Saito, K. & Kihara, K. C-reactive protein as a biomarker for urological cancers. Nat. Rev. Urol. 8, 659–666 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. Meyer, M. S. et al. Genetic variation in RNASEL associated with prostate cancer risk and progression. Carcinogenesis 31, 1597–1603 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Beuten, J. et al. Single and multivariate associations of MSR1, ELAC2, and RNASEL with prostate cancer in an ethnic diverse cohort of men. Cancer Epidemiol. Biomarkers Prev. 19, 588–599 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Merrimen, J. L., Jones, G. & Srigley, J. R. Is high grade prostatic intraepithelial neoplasia still a risk factor for adenocarcinoma in the era of extended biopsy sampling? Pathology 42, 325–329 (2010).

    Article  PubMed  Google Scholar 

  36. Mahmud, S. M. et al. Use of non-steroidal anti-inflammatory drugs and prostate cancer risk: a population-based nested case-control study. PLoS ONE 6, e16412 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mahmud, S. M., Franco, E. L. & Aprikian, A. G. Use of nonsteroidal anti-inflammatory drugs and prostate cancer risk: a meta-analysis. Int. J. Cancer 127, 1680–1691 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Roehrborn, C. G., Kaplan, S. A. & Noble, B. W. The impact of acute or chronic inflammation in baseline biopsy on the risk of clinical progression of BPH: results from the MTOPS study. J. Urol. 173, 364 (2005).

    Google Scholar 

  39. Robert, G. et al. Inflammation in benign prostatic hyperplasia: a 282 patients' immunohistochemical analysis. Prostate 69, 1774–1780 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kramer, G., Mitteregger, D. & Marberger, M. Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur. Urol. 51, 1202–1216 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Schauer, I. G. & Rowley, D. R. The functional role of reactive stroma in benign prostatic hyperplasia. Differentiation 82, 200–210 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Schenk, J. M. et al. Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am. J. Epidemiol. 171, 571–582 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  43. St. Sauver, J. L. et al. Associations between C-reactive protein and benign prostatic hyperplasia/lower urinary tract symptom outcomes in a population-based cohort. Am. J. Epidemiol. 169, 1281–1290 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Sutcliffe, S. et al. Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. BJU Int. 110, 1050–1059 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Roehrborn, C. G. et al. Baseline data from the Combination of Avodart and Tamsulosin (CombAT) trial: relationships between body mass index (BMI) and LUTS/BPH measures. Eur. Urol. Suppl. 5, 195 (2006).

    Google Scholar 

  46. Hammarsten, J. & Hogstedt, B. Calculated fast-growing benign prostatic hyperplasia—a risk factor for developing clinical prostate cancer. Scand. J. Urol. Nephrol. 36, 330–338 (2002).

    Article  PubMed  Google Scholar 

  47. Hammarsten, J. & Hogstedt, B. Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia. Eur. Urol. 39, 151–158 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Hammarsten, J. & Hogstedt, B. Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia. Blood Press. 8, 29–36 (1999).

    Article  CAS  PubMed  Google Scholar 

  49. Sarma, A. V. et al. Associations between diabetes and clinical markers of benign prostatic hyperplasia among community-dwelling Black and White men. Diabetes Care 31, 476–482 (2008).

    Article  PubMed  Google Scholar 

  50. McLaren, I. D., Jerde, T. J. & Bushman, W. Role of interleukins, IGF and stem cells in BPH. Differentiation 82, 237–243 (2011).

    Article  CAS  PubMed  Google Scholar 

  51. Nemesure, B., Wu, S. Y., Hennis, A. & Leske, M. C. Central adiposity and prostate cancer in a Black population. Cancer Epidemiol. Biomarkers Prev. 21, 851–858 (2012).

    Article  PubMed  Google Scholar 

  52. Wright, M. E. et al. Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality. Cancer 109, 675–684 (2007).

    Article  PubMed  Google Scholar 

  53. Andersson, S. O. et al. Body size and prostate cancer: a 20-year follow-up study among 135,006 Swedish construction workers. J. Natl Cancer Inst. 89, 385–389 (1997).

    Article  CAS  PubMed  Google Scholar 

  54. Dimitropoulou, P. et al. Association of obesity with prostate cancer: a case-control study within the population-based PSA testing phase of the ProtecT study. Br. J. Cancer 104, 875–881 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Albanes, D. et al. Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J. Natl Cancer Inst. 101, 1272–1279 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hayashi, N. et al. The impact of hypertriglyceridemia on prostate cancer development in patients aged >/=60 years. BJU Int. 109, 515–519 (2012).

    Article  PubMed  Google Scholar 

  57. van Hemelrijck, M. et al. Prostate cancer risk in the Swedish AMORIS study: the interplay among triglycerides, total cholesterol, and glucose. Cancer 117, 2086–2095 (2011).

    Article  CAS  PubMed  Google Scholar 

  58. Yeh, H. C. et al. A prospective study of the associations between treated diabetes and cancer outcomes. Diabetes Care 35, 113–118 (2012).

    Article  PubMed  Google Scholar 

  59. Mantzoros, C. S. et al. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br. J. Cancer 76, 1115–1118 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rowlands, M. A. et al. Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case-control study ProtecT. Cancer Res. 72, 503–515 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Tindall, D. J. & Rittmaster, R. S. The rationale for inhibiting 5alpha-reductase isoenzymes in the prevention and treatment of prostate cancer. J. Urol. 179, 1235–1242 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Nacusi, L. P. & Tindall, D. J. Targeting 5alpha-reductase for prostate cancer prevention and treatment. Nat. Rev. Urol. 8, 378–384 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gann, P. H. et al. A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia. Prostate 26, 40–49 (1995).

    Article  CAS  PubMed  Google Scholar 

  64. St. Sauver, J. L. et al. Associations between longitudinal changes in serum estrogen, testosterone, and bioavailable testosterone and changes in benign urologic outcomes. Am. J. Epidemiol. 173, 787–796 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Kristal, A. R. et al. Serum steroid and sex hormone-binding globulin concentrations and the risk of incident benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am. J. Epidemiol. 168, 1416–1424 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Roddam, A. W., Allen, N. E., Appleby, P. & Key, T. J. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J. Natl Cancer Inst. 100, 170–183 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Morgentaler, A. & Traish, A. M. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur. Urol. 55, 310–320 (2009).

    Article  PubMed  Google Scholar 

  68. Wurzel, R., Ray, P., Major-Walker, K., Shannon, J. & Rittmaster, R. The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. 10, 149–154 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. Zhu, Y. S. & Imperato-McGinley, J. L. 5alpha-reductase isozymes and androgen actions in the prostate. Ann. NY Acad. Sci. 1155, 43–56 (2009).

    Article  CAS  PubMed  Google Scholar 

  70. Balistreri, C. R., Caruso, C., Carruba, G., Miceli, V. & Candore, G. Genotyping of sex hormone-related pathways in benign and malignant human prostate tissues: data of a preliminary study. OMICS 15, 369–374 (2011).

    Article  CAS  PubMed  Google Scholar 

  71. Klotsman, M., Weinberg, C. R., Davis, K., Binnie, C. G. & Hartmann, K. E. A case-based evaluation of SRD5A1, SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH. Pharmacogenomics J. 4, 251–259 (2004).

    Article  CAS  PubMed  Google Scholar 

  72. Mononen, N. et al. Androgen receptor CAG polymorphism and prostate cancer risk. Hum. Genet. 111, 166–171 (2002).

    Article  CAS  PubMed  Google Scholar 

  73. Tang, L. et al. Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Carcinogenesis 32, 1500–1506 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Habuchi, T. et al. Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect. Cancer Res. 60, 5710–5713 (2000).

    CAS  PubMed  Google Scholar 

  75. McIntyre, M. H. et al. Prostate cancer risk and ESR1 TA, ESR2 CA repeat polymorphisms. Cancer Epidemiol. Biomarkers Prev. 16, 2233–2236 (2007).

    Article  CAS  PubMed  Google Scholar 

  76. Chae, Y. K., Huang, H. Y., Strickland, P., Hoffman, S. C. & Helzlsouer, K. Genetic polymorphisms of estrogen receptors alpha and beta and the risk of developing prostate cancer. PLoS ONE 4, e6523 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Kote-Jarai, Z. et al. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat. Genet. 43, 785–791 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Herlev Hospital, Copenhagen University Hospital, the Jascha Foundation, and the University of Copenhagen.

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  1. 54N5 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK-2730, Denmark

    David D. Ørsted & Stig E. Bojesen

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D. D. Ørsted researched and wrote this article, as well as making significant contributions towards discussions of contents. S. E. Bojesen discussed content with D. D. Ørsted and reviewed the manuscript prior to publication.

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Ørsted, D., Bojesen, S. The link between benign prostatic hyperplasia and prostate cancer. Nat Rev Urol 10, 49–54 (2013). https://doi.org/10.1038/nrurol.2012.192

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