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Effect of CYP17 and PSA gene polymorphisms on prostate cancer risk and circulating PSA levels in the Slovak population

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Abstract

Cytochrome P-450c17α (CYP17) and prostate-specific antigen (PSA) genes, which are involved in the androgen metabolism cascade, have been studied as possible candidates for genetic influences on prostate cancer development. Contradictory results prompted us to evaluate the frequencies of polymorphisms in the CYP17 and PSA genes as well as the association between these genetic variants and serum PSA levels in prostate cancer patients and men routinely screened for prostate cancer with PSA in the Slovak male population. The CYP17 and PSA polymorphisms were determined by the PCR–RFLP analysis in 197 Caucasian prostate cancer patients and 256 Caucasian controls. We did not find any association between the CYP17 and PSA genotypes and prostate cancer risk overall, or by grade. Also the total serum PSA levels in the cases with the AG or AA genotype were not significantly higher than in the men with the GG genotype (P > 0.05). Our study did not provide support for the hypothesized relationship between CYP17 and PSA gene polymorphisms and prostate cancer in the Slovak male population.

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References

  1. Grönberg H (2003) Prostate cancer epidemiology. Lancet 361:859–864

    Article  PubMed  Google Scholar 

  2. Sanchez-Visconti G, Herrero L, Rabadan M, Pereira I, Ruiz-Torres A (1995) Ageing and prostate: age-related changes in androgen receptors of epithelial cells from benign hypertrophic glands compared with cancer. Mech Ageing Dev 82:19–29

    Article  PubMed  CAS  Google Scholar 

  3. Brawley OW, Jani AB, Master V (2007) Prostate cancer and race. Curr Probl Cancer 31:211–225

    Article  PubMed  Google Scholar 

  4. Khan N, Afaq F, Mukhtar H (2010) Lifestyle as risk factor for cancer: evidence from human studies. Cancer Lett 293:133–143

    Article  PubMed  CAS  Google Scholar 

  5. Stein QP and Flanagan JD (2010) Genetic and familial factors influencing breast, colon, prostate and lung cancers. S D Med Spec No.:16–22

  6. Moorthy HK, Venugopal P (2008) Strategies for prostate cancer prevention: review of the literature. Indian J Urol 24:295–302

    Article  PubMed  Google Scholar 

  7. Imamoto T, Suzuki H, Utsumi T, Endo T, Takano M et al (2009) Association between serum sex hormone levels and prostate cancer: effect of prostate cancer on serum testosterone levels. Future Oncol 5:1005–1013

    Article  PubMed  CAS  Google Scholar 

  8. Payne AH, Hales DB (2004) Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 25:947–970

    Article  PubMed  CAS  Google Scholar 

  9. Twiddy AL, Leon CG, Wasan KM (2010) Cholesterol as a potential target for castration-resistant prostate cancer. Pharm Res 28:423–437

    Article  PubMed  Google Scholar 

  10. Miller WL (2005) Disorders of androgen synthesis-from cholesterol to dehydroepiandrosterone. Med Princ Pract 14:58–68

    Article  PubMed  Google Scholar 

  11. Vis AN, Schröder FH (2009) Key targets of hormonal treatment of prostate cancer. Part 2: the androgen receptor and 5alpha-reductase. BJU Int 104:1191–1197

    Article  PubMed  CAS  Google Scholar 

  12. Penning TM (2010) New frontiers in androgen biosynthesis and metabolism. Curr Opin Endocrinol Diabetes Obes 17:233–239

    Article  PubMed  CAS  Google Scholar 

  13. Lamont KR, Tindall DJ (2010) Androgen regulation of gene expression. Adv Cancer Res 107:137–162

    Article  PubMed  CAS  Google Scholar 

  14. Balk SP, Ko YJ, Bubley GJ (2003) Biology of prostate-specific antigen. J Clin Oncol 21:383–391

    Article  PubMed  CAS  Google Scholar 

  15. Botchorishvili G, Matikainen MP, Lilja H (2009) Early prostate-specific antigen changes and the diagnosis and prognosis of prostate cancer. Curr Opin Urol 19:221–226

    Article  PubMed  Google Scholar 

  16. Schröder FH, Roobol MJ (2009) Defining the optimal prostate-specific antigen threshold for the diagnosis of prostate cancer. Curr Opin Urol 19:227–231

    Article  PubMed  Google Scholar 

  17. Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO, Trapman J (1996) Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem 271:6379–6388

    Article  PubMed  CAS  Google Scholar 

  18. Xue WM, Coetzee GA, Ross RK, Irvine R, Kolonel L et al (2001) Genetic determinants of serum prostate-specific antigen levels in healthy men from a multiethnic cohort. Cancer Epidemiol Biomarkers Prev 10:575–579

    PubMed  CAS  Google Scholar 

  19. Cohen P, Peehl D, Graves H, Rosenfeld R (1994) Biological effects of prostate specific antigen (PSA) as an IGF binding protein-3 (IGFBP-3) protease. J Endocrinol 142:407–415

    Article  PubMed  CAS  Google Scholar 

  20. Cramer S, Chen Z, Peehl D (1996) Prostate specific antigen cleaves parathyroid hormone-related protein (PTHrP) in the PTH-like domain: inactivation of PTHrP-stimulated cAMP accumulation in mouse osteoblasts. J Urol 156:526–531

    Article  PubMed  CAS  Google Scholar 

  21. Dallas SL, Zhao S, Cramer SD, Chen Z, Peehl DM et al (2005) Preferential production of latent transforming growth factor beta-2 by primary prostatic epithelial cells and its activation by prostate-specific antigen. J Cell Physiol 202:361–370

    Article  PubMed  CAS  Google Scholar 

  22. Schaid DJ, Guenther JC, Christensen GB, Hebbring S, Rosenow C et al (2004) Comparison of microsatellites versus single-nucleotide polymorphisms in a genome linkage screen for prostate cancer-susceptibility Loci. Am J Hum Genet 75:948–965

    Article  PubMed  CAS  Google Scholar 

  23. Reynolds MA, Kastury K, Groskopf J, Schalken JA, Rittenhouse H (2007) Molecular markers for prostate cancer. Cancer Lett 249:5–13

    Article  PubMed  CAS  Google Scholar 

  24. Sharp L, Cardy AH, Cotton SC, Little J (2004) CYP17 gene polymorphisms: prevalence and associations with hormone levels and related factors. A HuGE review. Am J Epidemiol 160:729–740

    Article  PubMed  CAS  Google Scholar 

  25. Miyoshi Y, Iwao K, Ikeda N, Egawa C, Noguchi S (2000) Genetic polymorphism in CYP17 and breast cancer risk in Japanese women. Eur J Cancer 36:2375–2379

    Article  PubMed  CAS  Google Scholar 

  26. Wang LZ, Sato K, Tsuchiya N, Yu JG, Ohyama C et al (2003) Polymorphisms in prostate-specific antigen (PSA) gene, risk of prostate cancer, and serum PSA levels in Japanese population. Cancer Lett 202:53–59

    Article  PubMed  CAS  Google Scholar 

  27. Wang F, Zou YF, Feng XL, Su H, Huang F (2011) CYP17 gene polymorphisms and prostate cancer risk: a meta-analysis based on 38 independent studies. Prostate 71:1167–1177

    Article  PubMed  CAS  Google Scholar 

  28. Sobti RC, Gupta L, Singh SK, Seth A, Kaur P et al (2008) Role of hormonal genes and risk of prostate cancer: gene–gene interactions in a North Indian population. Cancer Genet Cytogenet 185:78–85

    Article  PubMed  CAS  Google Scholar 

  29. Binnie MC, Alexander FE, Heald C, Habib FK (2005) Polymorphic forms of prostate specific antigen and their interaction with androgen receptor trinucleotide repeats in prostate cancer. Prostate 63:309–315

    Article  PubMed  CAS  Google Scholar 

  30. Cicek MS, Liu X, Casey G, Witte JS (2005) Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11alpha in prostate cancer risk and aggressiveness. Cancer Epidemiol Biomarkers Prev 14:2173–2177

    Article  PubMed  CAS  Google Scholar 

  31. Hamada A, Danesi R, Price DK, Sissung T, Chau C et al (2007) Association of a CYP17 polymorphism with overall survival in Caucasian patients with androgen-independent prostate cancer. Urology 70:217–220

    Article  PubMed  Google Scholar 

  32. Stanford JL, Noonan EA, Iwasaki L, Kolb S, Chadwick RB et al (2002) A polymorphism in the CYP17 gene and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 11:243–247

    PubMed  CAS  Google Scholar 

  33. Jesser C, Mucci L, Farmer D, Moon C, Li H et al (2008) Effects of G/A polymorphism, rs266882, in the androgen response element 1 of the PSA gene on prostate cancer risk, survival and circulating PSA levels. Br J Cancer 99:1743–1747

    Article  PubMed  CAS  Google Scholar 

  34. Xue W, Irvine RA, Yu MC, Ross RK, Coetzee GA et al (2000) Susceptibility to prostate cancer: interaction between genotypes at the androgen receptor and prostate-specific antigen loci. Cancer Res 60:839–841

    PubMed  CAS  Google Scholar 

  35. Allen NE, Forrest MS, Key TJ (2001) The association between polymorphisms in the CYP17 and 5alpha-reductase (SRD5A2) genes and serum androgen concentrations in men. Cancer Epidemiol Biomarkers Prev 10:185–189

    PubMed  CAS  Google Scholar 

  36. Tajtakova M, Pidanicova A, Valansky L, Lachvac L, Nagy V et al (2010) Serum level of IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and single nucleotide polymorphism in PSA and CYP17 gene may contribute to early diagnostics of prostate cancer. Neoplasma 57:118–122

    Article  PubMed  CAS  Google Scholar 

  37. dos Santos RM, de Jesus CM, Trindade Filho JC, Trindade JC, de Camargo JL et al (2008) PSA and androgen-related gene (AR, CYP17, and CYP19) polymorphisms and the risk of adenocarcinoma at prostate biopsy. DNA Cell Biol 27:497–503

    Article  PubMed  Google Scholar 

  38. Lunn RM, Bell DA, Mohler JL, Taylor JA (1999) Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2). Carcinogenesis 20:1727–1731

    Article  PubMed  CAS  Google Scholar 

  39. Kittles RA, Panguluri RK, Chen W, Massac A, Ahaghotu C et al (2001) Cyp17 promoter variant associated with prostate cancer aggressiveness in African Americans. Cancer Epidemiol Biomarkers Prev 10:943–947

    PubMed  CAS  Google Scholar 

  40. Wadelius M, Andersson AO, Johansson JE, Wadelius C, Rane E (1999) Prostate cancer associated with CYP17 genotype. Pharmacogenetics 9:635–639

    Article  PubMed  CAS  Google Scholar 

  41. Haiman CA, Stampfer MJ, Giovannucci E, Ma J, Decalo NE et al (2001) The relationship between a polymorphism in CYP17 with plasma hormone levels and prostate cancer. Cancer Epidemiol Biomarkers Prev 10:743–748

    PubMed  CAS  Google Scholar 

  42. Gsur A, Bernhofer G, Hinteregger S, Haidinger G, Schatzl G et al (2000) A polymorphism in the CYP17 gene is associated with prostate cancer risk. Int J Cancer 87:434–437

    Article  PubMed  CAS  Google Scholar 

  43. Yamada Y, Watanabe M, Murata M, Yamanaka M, Kubota Y et al (2001) Impact of genetic polymorphisms of 17-hydroxylase cytochrome P-450 (CYP17) and steroid 5alpha-reductase type II (SRD5A2) genes on prostate-cancer risk among the Japanese population. Int J Cancer 92:683–686

    Article  PubMed  CAS  Google Scholar 

  44. Souiden Y, Mahdouani M, Chaieb K, Elkamel R, Mahdouani K (2010) CYP17 gene polymorphism and prostate cancer susceptibility in a Tunisian population. Cancer Epidemiol 45(10):772–774

    Google Scholar 

  45. Habuchi T, Liqing Z, Suzuki T, Sasaki R, Tsuchiya N et al (2000) 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

    PubMed  CAS  Google Scholar 

  46. Chang B, Zheng SL, Isaacs SD, Wiley KE, Carpten JD et al (2001) Linkage and association of CYP17 gene in hereditary and sporadic prostate cancer. Int J Cancer 95:354–359

    Article  PubMed  CAS  Google Scholar 

  47. Latil AG, Azzouzi R, Cancel GS, Guillaume EC, Cochan-Priollet B et al (2001) Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways. Cancer 92:1130–1137

    Article  PubMed  CAS  Google Scholar 

  48. Madigan MP, Gao YT, Deng J, Pfeiffer RM, Chang BL et al (2003) CYP17 polymorphisms in relation to risks of prostate cancer and benign prostatic hyperplasia: a population-based study in China. Int J Cancer 107:271–275

    Article  PubMed  CAS  Google Scholar 

  49. Ntais C, Polycarpou A, Ioannidis JP (2003) Association of the CYP17 gene polymorphism with the risk of prostate cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 12:120–126

    PubMed  CAS  Google Scholar 

  50. Cotter MP, Gern RW, Ho GY, Chang RY, Burk RD (2002) Role of family history and ethnicity on the mode and age of prostate cancer presentation. Prostate 50:216–221

    Article  PubMed  Google Scholar 

  51. Zmuda JM, Cauley JA, Kuller LH, Ferrell RE (2001) A common promotor variant in the cytochrome P450c17alpha (CYP17) gene is associated with bioavailability testosterone levels and bone size in men. J Bone Miner Res 16:911–917

    Article  PubMed  CAS  Google Scholar 

  52. Gsur A, Preyer M, Haidinger G, Zidek T, Madersbacher S et al (2003) Polymorphic CAG repeats in the androgen receptor gene, prostate-specific antigen polymorphism and prostate cancer risk. Carcinogenesis 23:1647–1651

    Article  Google Scholar 

  53. Lai J, Kedda MA, Hinze K, Smith RL, Yaxley J et al (2007) PSA/KLK3 AREI promoter polymorphism alters androgen receptor binding and is associated with prostate cancer susceptibility. Carcinogenesis 28:1032–1039

    Article  PubMed  CAS  Google Scholar 

  54. Sävblom C, Giwercman A, Malm J, Halldén C, Lundin K et al (2009) Association between polymorphisms in the prostate-specific antigen (PSA) promoter and release of PSA. Int J Androl 32:479–485

    Article  PubMed  Google Scholar 

  55. Medeiros R, Morais A, Vasconcelos A, Costa S, Pinto D et al (2002) Linkage between polymorphisms in the prostate specific antigen ARE1 gene region, prostate cancer risk, and circulating tumor cells. Prostate 53:88–94

    Article  PubMed  CAS  Google Scholar 

  56. Chiang CH, Chen KK, Chang LS, Hong C (2004) The impact of polymorphism on prostate specific antigen gene on the risk, tumor volume and pathological stage ofprostate cancer. J Urol 171:1529–1532

    Article  PubMed  CAS  Google Scholar 

  57. Rao A, Chang BL, Hawkins G, Hu JJ, Rosser CJ et al (2003) Analysis of G/A polymorphism in the androgen response element I of the PSA gene and its interactions with the androgen receptor polymorphisms. Urology 61:864–869

    Article  PubMed  Google Scholar 

  58. Salinas CA, Austin MA, Ostrander EO, Stanford JL (2005) Polymorphisms in the androgen receptor and the prostate-specific antigen genes and prostate cancer risk. Prostate 65:58–65

    Article  PubMed  CAS  Google Scholar 

  59. Shibahara T, Onishi T, Franco OE, Arima K, Nishikawa K et al (2006) A G/A polymorphism in the androgen response element 1 of prostate-specific antigen gene correlates with the response to androgen deprivation therapy in Japanese population. Anticancer Res 26:3365–3371

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Ministry of Health of the Slovak Republic under the project 2007/45-UK-10 “Genetic polymorphism of xenobiotic metabolising enzymes and susceptibility to prostate cancer in the Slovak population” and by grant MH SR 2007/57-UK-17. This work was supported by project “CENTER OF EXCELLENCE FOR RESEARCH ON PERSONALIZED THERAPY (CEVYPET)”, code 2622012053, co-financed from EU sources and European Regional Development Fund. The authors are grateful to Dr N. A. Yeboah for critical reading of the manuscript and wish to thank Mrs M. Martinčeková, M. Pisková and B. Vidová for their technical assistance.

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Correspondence to Monika Kmeťová Sivoňová.

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Sivoňová, M.K., Dobrota, D., Dušenka, R. et al. Effect of CYP17 and PSA gene polymorphisms on prostate cancer risk and circulating PSA levels in the Slovak population. Mol Biol Rep 39, 7871–7880 (2012). https://doi.org/10.1007/s11033-012-1631-y

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  • DOI: https://doi.org/10.1007/s11033-012-1631-y

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