PSA ciągle najlepszy marker nowotworowy, modyfi kacje testu i nowe markery raka stercza

• Authors: Michał Braczkowski , Michał Białożyt , Ryszard Braczkowski , Zdzisława Kondera-Anasz

Title variants

EN

PSA still the best cancer marker, PSA test modifi cations and new prostate cancer markers

• Languages of publication: PL

Abstracts

PL

Od wielu lat specyficzny antygen sterczowy (PSA) uważany jest za najlepszy, choć daleki od ideału marker nowotworowy. Podstawowy cel jego zastosowania to pomoc w rozpoznawaniu i różnicowaniu raka i łagodnego przerostu gruczołu krokowego. Wartość markerów nowotworowych w przypadku raka stercza jest szczególnie ważna wobec faktu wieloletniego bezobjawowego rozwoju tego nowotworu, a szczególnego znaczenia nabiera ona w ostatnich latach, gdy obserwujemy stale wzrastającą tendencję do zachorowań. W pracy przedstawiono zalety i wady testu PSA, jego modyfikacje (np. testy dynamiczne) wprowadzone w celu zwiększenia czułości i specyficzności oraz – co za tym idzie – wiarygodności testu. W dalszej kolejności opisano proenzymy oraz formy prekursorowe PSA i możliwości wykorzystania ich w diagnostyce. W drugiej części pracy opisano nowe, potencjalne markery raka stercza, których próby wprowadzenia wiążą się z rozwojem technik biologii molekularnej. Należy tu wymienić kolejne kalikreiny (PSA jest także przedstawicielem tej rodziny), EPCA-2, PCA3, AMACR, produkty rearanżacji i fuzji genów, hipermetylacja GSTP1, wolne DNA w surowicy krwi, przeciwciała i szereg innych o nieco mniejszym znaczeniu.

EN

The prostate-specific antigen is considered to be the most eff ective, though far from ideal, tumor marker. The basic aim of its application is to diagnose and diff erentiate between cancer and benign prostatic hyperplasia. The value of markers in case of prostate cancer is of particular importance, because of the long-term asymptomatic development. And recently, these values have become even more signifi cant, since there has been an increasing tendency to suff er from the disease. Our study presents advantages and imperfections of the PSA test, its modifi cations (e.g. dynamic tests) introduced in order to increase the specificity and sensitivity of the test, and thus its reliability. Subsequently proenzymes and PSA precursor forms as well as the opportunities for their use in the diagnostics are described. The rest of the article is devoted to the description of new potential prostate cancer markers, the implementation of which is closely associated with the development of molecular biology techniques. Among them the most important are: new kallikreins (PSA is also the member of kallikreins family), EPCA-2, PCA3, AMACR, products of gene fusion and rearrangements, GSTP1 hypermethlation, free non-cellular DNA and some antibodies.

Keywords

EN

PSA; benign prostatic hyperplasia; biologia molekularna; cancer markers; markery nowotworowe; molecularbiology; new prostate cancer markers; nowemarkery raka stercza; prostate cancer; rak stercza; łagodny przerost stercza

Discipline

• MEDICINE: MEDICINE

• Publisher: Śląski Uniwersytet Medyczny w Katowicach
• Journal: Annales Academiae Medicae Silesiensis
• Year: 2011
• Volume: 65
• Issue: 1-2
• Pages: 89–98

Contributors

author

Michał Braczkowski

• Wyższa Szkoła Medyczna w Sosnowcu

author

Michał Białożyt

• Szpital im. Prof. E. Michałowskiego w Katowicach

author

Ryszard Braczkowski

• Katedra Zdrowia Publicznego Wydziału Zdrowia Publicznego Śląskiego Uniwersytetu Medycznego w Katowicach ul. Piekarska 18 41-902 Bytom, tel. [phone] do 5

author

Zdzisława Kondera-Anasz

• Katedra i Zakład Immunologii i Serologii Wydziału Farmaceutycznego z Oddziałem Medycyny Laboratoryjnej Śląskiego Uniwersytetu Medycznego w Katowicach

References

• 1. Mcshane L.M., Altman D.G., Sauerbrei W., Taube S.E., Gion M., Clark G.M. Reporting recomendations for Tumor Marker Prognostic Studies (REMARK). J. Natl. Cancer. Inst. 2005; 97: 1180 –1184.
• 2. Hayat M.J., Howlander N., Reichman M.E., Edwards B.K. Cancer statistics, trends and multiple primary cancer analysis from the Surveillance, Epidemiology, and End Results (SEER) Program. Oncologist 2007; 12: 20–37.
• 3. Jemal A., Siegel R., Ward E., Murray T., Xu J., Thun M.J. Cancer statistics 2007. Ca Cancer. J. Clin. 2007; 57: 43–46.
• 4. Wang M.C., Valanzuela L.A., Murphy G.P., Chu T.M. Purifi cation of human prostate-specifi c antigen. Invest. Urol. 1979; 17: 159–163.
• 5. Pepsidero L.D., Kurijama M, Wang M.C i wsp. Prostate antigen: a marker for prostate epithelial cells. J. Natl. Cancer. Inst. 1981; 66: 37– 42.
• 6. Yousef G.M., Diamandis E.P. Human, tissue kallikrein gene family: structure, function and association to disease. Endocrine Rev. 2001; 22: 184–204.
• 7. Lilja H., Christenson A., Dahlen U. i wsp. Prostate specifi c antigen in serum ocurs predominantly in complex with alpha 1- antichymotripsin. Clin. Chem. 1991; 37: 1618–1625.
• 8. Stennman U.H., Leinonen J., Alfhan H., Ranniko S., Tuhkannen K., Alfhan O. Complex between prostate specifi c antigen and alpha-I-antichymotripsin, the major form prostate specifi c antigen in serum of patients with prostatic cancer. Assay of the complex improves sensitivity for cancer. Cancer Res. 1991; 51: 222–226.
• 9. Oesterling J.E., Jacobsen S.J., Chute C.G. i wsp. Serum prostate specifi c antigen in a community-based population of healthy man. Establishment of age specifi c reference ranges. JAMA 1993; 279: 860–864.
• 10. Oesterling J.E. Age-specifi c reference ranges for serum PSA. N. Engl. J. Med. 1996; 335: 345–356.
• 11. Potter S.R, Partin A.W. Prostate cancer detection, staging and treatment of localised disease. Sem. Roentg. 1999; 34: 269–283.
• 12. Stennaman U.H., Abrahamsson P.A., Lilja H., Ekman P., Hammady F.C., Boccon- Gibbod L. Prognostic value of serum markers for prostate cancer. Scand. J. Urol. Nephrol. 2005; 2161–2181.
• 13. Thompson I.M., Pauler D.K., Goodman P.J. i wsp. Prevalence of prostate cancer among man with prostate specifi c antygen level 􀂔 4ng per milliliter. N. Engl. J. Med. 2004; 350: 2239–2246.
• 14. Ankerst D.P., Thompson I.M. Sensitivity and specifi ty of prostate-specifi c antigen for prostate cancer detection with high rates of biopsy verifi cation. Arch. Ital. Urol. Androl. 2006; 78: 125–129.
• 15. Rohde D., Mihelicic V. Does plasmatic dilution infl uence the validity of PSA-tests. Aktuelle Urol. 2007; 38: 113–143.
• 16. Rundle A., Richards C., Neugut A.I. Body composition, abdominal fat distribution, and prostate-specifi c antigen test results. Cancer Epidemiol. Biomarkers Prev. 2009; 18: 33–36.
• 17. Wever E.M., Draisma G., Heijnsdijk E. i wsp. Prostate-Specifi c Antigen Screening in the United States vs in the European Randomized Study of Screening for Prostate Cancer-Rotterdam. J. Natl. Cancer. Inst. 2010; 102: 352–355.
• 18. Babaian R.J., Fritsle H.A., Evans R.B. Prostate-specifi c antigen and prostate gland volume, correlation and clinical application. J. Clin. Lab. Anal. 1990; 18: 112–116.
• 19. Benson M.C., Whang I.S., Pantuck A. i wsp. Prostate specifi c antigen density; Means of distinguishing benign prostatic hypertophy and prostate cancer. J. Urol. 1992; 147: 815–816.
• 20. Kochańska-Dziurowicz A., Szewczyk W., Mielniczuk M, Kasperkiewicz K. Przydatność oznaczania surowiczego stężenia wolnej i całkowitej formy swoistego antygenu sterczowego (PSA) w zakresie stężeń PSA od 4,0 do 10,0 ng/ml w diagnostyce różnicowej łagodnego rozrostu i raka gruczołu krokowego. Urol. Pol. 1998; 51: 67–75.
• 21. Seaman E., Whang M., Olsson C.A., Katz A., Cooner W.H., Benson M.C. PSA density (PSAD), role in patient evaluation and management. Urol. Clin. North. Am. 1993; 20: 653–663.
• 22. Catalona W.J., Richie J.P., DeKermion J.B. i wsp. Comparison of prostate specifi c antigen concentration versus prostate specifi c density in the early detection of prostate cancer: receiver operating characteristic curves. J. Urol. 1994; 152: 2031–203
• 23. Kalish J., Cooner W.H., Graham S.D.jr. Serum PSA ajusted for volume of transition zone (PSAT) is more acurate than PSA adjusted for total gland volume (PSAD) in detecting adenocarcionoma of the prostate. Urology 1994; 43: 601–606.
• 24. Zlotta A.R., Djavan B., Marberger M., Schulman C. Prostate specifi c antigen density of the tranzition zone: a new eff ective parameter for prostate cancer prediction. J. Urol. 1997; 157: 1315–1321.
• 25. Schmid H-P., Prikler R., Sturgeon C.M., Semjonow A. Diagnosis of prostate Cancer – The Clinical use of prostate specifi c antigen. EAU Update Series 2003; 1: 3–8.
• 26. Berger, A., Deibl M., Steiner H.B. i wsp. Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk. Prostate 2005; 64: 240–245.
• 27. Catalona. , Loeb S. The PSA era is not over for prostate cancer. Eur. Urol. 2005: 48; 541–545.
• 28. Smith D.S., Catalona W.J. Rate of change in serum prostate-specifi c antigen levels as a method for prostate cancer detection. J. Urol. 1994; 152: 1163–1167.
• 29. Thompson I.M., Ankerst D.P., Chi C. i wsp. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J. Natl. Cancer. Inst. 2006; 98: 529–534.
• 30. Wolters T., Roobol M.J., Bangma C.H., Schröder F.H. Is prostate specifi c antigen velocity selective for clinically signifi cant prostate cancer in screening? European randomized study of screening for prostate cancer (Rotterdam). Eur. Urol. 2009; 55: 385–393.
• 31. Schmid H-P., McMeal J.E., Staney T.A. Observation on the doubling time of prostate cancer. The use of serial prostate-specifi c antigen in patients with untreated disease as a measure of increasing cancer volume. Cancer 1993; 71: 2031–2040.
• 32. Stephan C., Jung K., Lein M., Diamandis A.P. PSA and other tissue kallikreins for prostate cancer detection. Eur. J. Cancer 2007; 43: 1918–1926.
• 33. Catalona W.J., Partin A.W., Stawin K.M. i wsp. Use of percentage of free prostate specifi c antigen to enhance diff erentiation of prostate cancer from benign prostatic disease A prospective multicenter clinical trial. JAMA 1998; 279: 1542–1547.
• 34. Stephan C., Lein M., Jung K., Schnorr D., Loening S.A. The infl uence of prostate volume on the ratio of free to total prostate-specifi c antigen in serum of patients with prostate carcinoma and benign prostate hyperplasia. Cancer 1997; 79: 104–109.
• 35. Brawer M.K., Mayer G.E., Letran J.L. Measurment of complexed PSA improves specifi ty for early detection of prostate cancer. Urology 1998; 52: 372–378.
• 36. Mitchel I.D.C., Croal B.L., Dickie A., Cohen N.P., Ross I. A prospective study to evaluate the role of complexed prostate specifi c antigen and free/total prostate specifi c antigen ratio for the diagnosis of prostate cancer. J. Urol. 2001; 162: 1549–1553.
• 37. Djavan B., Remzi M., Zlotta A.R. i wsp. Complexed prostate specifi c antigen, complexed prostate specifi c antigen density of total and transition zone, complexed/total prostate-specifi c antigen ratio, free to total prostate-specifi c antigen ratio, density of total and trasition zone prostate specifi c antigen; results of multicenter European trial. Urology 2002; 60(suppl): 4–9.
• 38. Fillela X., Alcover J, Molina R., Corrla J.M., Carretero P., Balesta A.M. Measurment of complexed PSA in the diff erential diagnosis between prostate cancer and benign prostate hyperplasia. Prostate 2000; 42: 181–185.
• 39. Zhang W.M., Finne P., Leinonen J., Salo J., Stenman U.H. Detrmination of prostatespecifi c antigen complexed to alpha(2)- macroglobulin in serum increase the specifi ty of free to total PSA for prostate cancer. J. Urol. 2000; 56: 267–272.
• 40. Sokoll L.J., Chan D.W., Mikolajczyk S.D. i wsp. Proenzyme PSA for the early detection of prostate cancer in the 2,5 to 4,0 ng/ ml total PSA range: preleminary analyses. Urology 2003; 61: 274–276.
• 41. Khan M.A., Sokol L.J., Chan D.W. i wsp. Clinical utility of proPSA and „binign” PSA when percent fre PSA is less than 15%. Urology 2004; 64: 1160–1164.
• 42. Mikołajczyk S.D., Catalona W.J., Evans C.L. i wsp. Proenzyme forms of prostatespecifi c antigen in serum improve the detection of prostate cancer. Clin. Chem. 2004; 50: 1017–1025.
• 43. Jansen F.H., Roobol M., Jenster G., Schröder F.H., Bangma C.H. Screening for prostate cancer in 2008: the importance of molecular subforms of prostate-specifi c antigen and tissue kallikreins. Eur. Urol. 2009; 55: 563–674.
• 44. Tabar􀒿s G., Jung K., Reice J. i wsp. Free PSA forms in prostatic tissue and sera of prostate cancerpatients: analisis by 2-DE and western blotting of immunopurifi ed samples. Clin. Biochem. 2007; 40: 343–350.
• 45. Wang T.J., Slawin K.M., Rittenhouse H.G., Millar L.S., Mikolajczyk S.D. Benign prostatic hyperplasia-associated prostatespecifi c antigen (BPSA), shows unique reactivity with anti-PSA monoclonal antibodies Eur. J. Biochem. 2000; 267: 4040– 4045.
• 46. Canto E.I., Singh H., Shariat S.F. i wsp. Serum BPSA outperforms both total PSA and free PSA as predictor of prostatic enlargement in man without prostate cancer. Urology 2004; 63: 905–910.
• 47. Nurmikko P, Petterson K., Piironnen T., Huggoson J., Lilja H. Discrimination of prostate cancer from benign disease by plasma measurment of intact free prostatespecifi c antigen lacking an internal cleavage site at Lys145 – Lys146 Clin. Chem. 2001; 47: 1415–1423.
• 48. Irani J., Milet C., Levillain P., Dore B., Begon M., Aubert J. Serum to-urinary prostate specifi c antigen ratio: its impact in distingnishing proste cancer when serum prostate antigen level is 4 to 10 ng/ml. J. Urol. 1997, 157, 185–188.
• 49. Partin A.W., Catalona W.J., Finlay J.A. i wsp. Use of human glandular kallikrein 2 in the detection of prostate cancer: preleminary analisis. Urology 1999; 54: 839–845.
• 50. Sardana G., Dowell B., Diamandis E.P. Emerging biomarkers for the diagnosis and prognosis of prostate cancer. Clin. Chem. 2006; 54: 1951–1960.
• 51. Haese A., Graefen M., Steuber T. i wsp. Total and Gleason grade 4/5 cancer volumes are major contributors of human kallikrein 2, whereas free prostate-specifi c antigen is largely contributed by benign gland volume in serum from patients with prostate cancer or benign prostatic biopsies. J. Urol. 2003; 170: 2269–2273.
• 52. Kwiatkowski M. K., Recker F., Piironen T. i wsp. In prostatism patients the ratio of human glandular kallikrein to free PSA improves dicimination between prostate cancer and benign hyperplasia within the diagnostic “ gray zone” of total PSA 4 to 10 ng/ml. Urology 1998; 5: 360–365.
• 53. Haese A., Becker C., Noldus J. i wsp. Human glandular kallikrein 2 a potential serum marker for predicting the organ confi ned growth of prostate cancer. J. Urol. 2000; 163: 149–157.
• 54. Recker F., Kwiatkowski M.K., Piironen T. i wsp. Human glandular kallikrein as tool to improve discrimination of poorly diff erentiated and non organ-confi dent prostate cancer compared with prostate-specifi c antigen. Urology 2000; 55: 481–485.
• 55. Stephan C., Jung K., Nakamura T., Yousef G.M., Kristiansen G., Diamandis E. P. Serum human glandular kallikrein 2 (hk2) for distinguishing stage and grade of prostate cancer. Int. J. Urol. 2006; 13: 238–243.
• 56. Diamandis E.P., Okui A., Mitsui S. i wsp. Human kallikrein 11. Cancer Res. 2002; 62: 295–300.
• 57. Nakamura T., Scorilas A., Stephan C., Jung K., Soosaipillai A.R., Diamandis E.P. The usefulness of serum human kallikrein 11 for discriminating between prostate cancer and benign prostatic hyperplasia. Cancer Res. 2003; 63: 6534 –6546.
• 58. Beckett M.L., Wright G. L. jr. Characterization of a prostate carcinoma mucin like-antigen (PMA). Int. J. Cancer 1995; 62): 703–710.
• 59. Yu H., Rohan H. Role of the insulinlike growth factor family in cancer development and progression. J. Natl Cancer Inst. 2000; 92: 1472–1489.
• 60. Jain A., Mc Knight G.A., Fisher L.W. i wsp. Small integrin-binding proteins as serum markers for prostate cancer detection. Clin. Cancer Res. 2009; 15: 5199– 5207.
• 61. Getzenberg R.H., Pienta K.J., Huang E.Y. W., Coff ey D.S. Identifi cation of nuclear matrix proteins in the cancer and normal rat prostate. Cancer Res. 1991; 51: 6514–6520.
• 62. Paul B., Dhir R., Landsittel D, Hitchens M.R., Getzenberg R.H. Detection of Prostate Cancer with a Blood-Based Assay for Early Prostate Cancer Antigen. Cancer Res. 2005; 65: 4097–4100.
• 63. Dhir R., Vietmeier B., Arlotti J. i wsp. Early identifi cation of individualas with prostate cancer in negative biopsies. J. Urol. 2004; 171: 1419 –1423.
• 64. Lin D.W. Utility of novel tumor markers in the setting of elevated PSA. Urol Oncol. 2009; 27(3): 315–321.
• 65. Leman E.S., Cannon G.W., Trock B.J. i wsp. EPCA-2: Highly specifi c serum marker for prostate cancer. Urology 2007; 69: 714–720.
• 66. Leman E.S., Magheli A., Cannon G.W., Magold L., Partin A.W., Getzenberg R.H. Analysis of serum test for prostate cancer that detects a second epitope of EPCA-2. Prostate 2009; 69: 1188–1194.
• 67. Wanders R.J., Vreken P., Ferdinandusse S. i wsp. Peroxisomal metabolite transporters and peroxisomal diseases. Biochem. Soc. Trans. 2001; 29: 250–267.
• 68. Rhodes D.R., Barette T.R., Rubin M.A., Ghosh D., Chinnaiyan A.M. Meta-analysis of microarrays: interstudy validation of gene expression profi les reveals pathway dysregulation in prostate cancer. Cancer Res. 2002: 62: 4427–4433.
• 69. Jiang Z., Wu C.L., Woda B.A., Iczkowski K.A. i wsp. Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker. Histopathology 2004; 45: 218–225.
• 70. Sreecumar A., Laxman B., Rhodes D.R i wsp. Humoral immune response to alpha- methylacyl-CoA racemase and prostate cancer. J. Natl. Cancer Inst. 2004; 96: 834–843.
• 71. Tomlins S.A., Rhodes D.R., Perner S. i wsp. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005; 310: 644–648.
• 72. Laxman B., Tomlins S.A., Mehra R. i wsp. Noninvasive detection of TMPRSS2: ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia 2006; 8: 885–888.
• 73. Jhavar S., Brewer D., Edwards S. i wsp. Integration of ERG gene mapping and gene-expression profi ling identifi es distinct categories of human prostate cancer. BJU Int. 2009; 103: 1256–1269.
• 74. Bussemakers M.J.G., van Bokhoven A, Verhaegh G.W. i wsp. DD3; a new prostate- specifi c gene, highly overexpressed in prostate cancer. Cancer Res. 1999; 59: 5975–5979.
• 75. Grokskopf J., Aubin S.M.J., Deras I.L. i wsp. Aptima PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem 2006; 52: 1089–1095.
• 76. Hessels D., Gunnewiek J.K., van Oort I. i wsp. DD3PCA3 based molecular urine analises for the diagnosis of prostate cancer. Eur. Urol. 2003; 44: 8–15.
• 77. Tinzl M., Marberger M., Horvath S, Chypre C. i wsp. DD3PCA3 RNA analysis in urine – a new perspective for detecting prostate cancer. Eur. Urol. 2004; 46: 182–187.
• 78. de-Kok J.B., Verhaegh G.W., Roelofs R.W. i wsp. DD3(PCA3) a very specifi c marker to detect prostate tumors. Cancer Res. 2002; 62: 2695–2698.
• 79. Laxman B., Morris D.S., Yu J. i wsp. A fi rst-generation multiplex biomarker analysis of urine for early detection of prostate cancer. Cancer Res. 2008 68: 645–649.
• 80. Ouyang B., Bracken B., Burke B., Chung E., Liang J., Ho S.M. A duplex quantitative polymerase chain reaction assay based on quantifi cation of alpha-methylacyl-CoA racemase transcripts of Prostate Cancer Antigen 3 in urine sediments improved diagnostic accuracy for prostate cancer. J. Urol, 2009, 181, 2508–2513.
• 81. Hoff mann W., Jagla W., Wiede A. Molecular medicine of TFF-peptides: from gut to brain. Histol. Histopathol. 2001; 16: 319–334.
• 82. Vestergaard EM, Borre M, Poulsen SS, Nexř E, Třrring N Plasma levels of trefoil factors are increased in patients with advanced prostate cancer. Clin. Cancer Res. 2006; 12: 807–812.
• 83. Kristiansen G., Fritzsche F.R., Wassermann K. i wsp. GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue based diagnostics. Br. J. Cancer 2008; 99: 939–948.
• 84. Verma M., Srivastava S. Epigenetyka nowotworów: implikacje dla wczesnego wykrywania i zapobiegania. Lancet Oncol. (PL) 2003; 2: 121–131.
• 85. Jerónimo C., Usadel H., Henrique R i wsp. Quantitative GSTP1 hypermethylation in bodily fl uids of patients with prostate cancer. J. Natl. Cancer Inst. 2001; 93: 1747–1752.
• 86. Roupert N., Hupertan V., Yates D.R Molecular detection of localized prostate cancer using quantitative methylation-specifi c PCR on urinary cells obtained following prostate massage. Clin. Cancer Res. 2007; 13: 1720–1725.
• 87. Mandel P., Metais P. Les accedes nucleiques du plasma sanguine che l’homme C R Acad Sci Paris. 1948; 142: 241–243.
• 88. Leon S.A., Shapiro B., Sklaroff D.M., Yaros M.J. Free DNA in the serum of cancer patients and the eff ect of therapy. Cancer Res. 1977; 37: 646–650.
• 89. Sozzi G., Conte D., Mariani L. i wsp. Analysis of circulating tumor DNA in plasma at diagnosis and during follow up of lung cancer patients. Cancer Res. 2001; 61: 4675–4678.
• 90. Wu T.L., Zhang D., Chia J.H., Tsao K.H., Sun C.F. i wsp. Cell-free DNA: measurement in various carcinomas and establishment of normal reference range. Clin. Chim. Acta. 2002; 321: 77–87.
• 91. Boddy J.L., Gal S., Malone P.R., Harris A.L., Wainscoat J.S. Prospective study of quantifi cation of plasma DNA levels in the diagnosis of malignant versus benign prostate disease. Clin. Cancer Res. 2005; 11: 1394–1399.
• 92. Cassiano C.A., Mediavilla-Varela M., Tan E.M. Tumor-associated antigen arrays for the serological diagnosis of cancer. Moll Cell Proteomics. 2006; 5: 1745–1759.
• 93. Bradley S.V., Oravecz-Wilson K.I. i wsp. Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer. Cancer Res. 2005; 65: 26–33.
• 94. Vickers A.J., Savage C., O’Brien M.F., Lilja H. Systematic review of pretreatment prostate-specifi c antigen velocity and doubling time as predictors for prostate cancer. J. Clin. Oncol. 2009; 27: 398–403.
• 95. Ross, R.K., Pike, M.C., Coetzee, G.A. i wsp. Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Res. 1998; 58: 4497– 4504.
• 96. Xue W., Irvine R.A., Yu M.C., Ross R.K., Coetze G. A., Ingles S.A. Susceptibility to prostate cancer: interaction between genotypes at the androgen receptor and prostate-specifi c antigen loci. Cancer Res. 2000; 60: 839–841.
• 97. Meyer A. Dörk T., Bremer M., Baumann R., Karstens J.H., Machtens S. ATM missense variant P1054R predisposes to prostate cancer. Radiother. Oncol. 2007; 83: 283–288.
• 98. Chen M., Huang Y.C., Yang S. i wsp. Common variants at 8q24 are associated with prostate cancer risk in Taiwanese men. Prostate 2010; 70: 502–507.

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