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Lack of association between the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphism and the risk of benign prostatic hyperplasia in Caucasian men

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Abstract

Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is an important metabolic process during which steroids are converted to more easily excreted compounds in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphism and benign prostatic hyperplasia. 421 blood samples were obtained from 138 consecutive patients diagnosed with benign prostatic hypeplasia (BPH group) and 283 healthy volunteers (control group). A(TA)6TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. No significant differences were observed between the BPH group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P = 0.39). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA)7) vs. TA(6)/TA(7) + TA(6)/TA(6)) (P = 0.31). Our data suggest that the TA repeat polymorphism of UGT1A1 is not associated with increased BPH risk susceptibility in Caucasian men.

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References

  1. Rhodes T, Girman CJ, Jacobsen SJ, Roberts RO, Guess HA, Lieber MM (1999) Longitudinal prostate growth rates during 5 years in randomly selected community men 40 to 79 years old. J Urol 161(4):1174–1179. doi:10.1016/S0022-5347(01)61621-5

    Article  PubMed  CAS  Google Scholar 

  2. Girman CJ, Jacobsen SJ, Guess HA, Oesterling JE, Chute CG, Panser LA, Lieber MM (1995) Natural history of prostatism: relationship among symptoms, prostate volume and peak urinary flow rate. J Urol 153(5):1510–1515. doi:10.1016/S0022-5347(01)67448-2

    Article  PubMed  CAS  Google Scholar 

  3. Vesely S, Knutson T, Damber JE, Dicuio M, Dahlstrand C (2003) Relationship between age, prostate volume, prostate-specific antigen, symptom score and uroflowmetry in men with lower urinary tract symptoms. Scand J Urol Nephrol 37(4):322–328. doi:10.1080/00365590310014760

    Article  PubMed  Google Scholar 

  4. Farnsworth WE (1996) Roles of estrogen and SHBG in prostate physiology. Prostate 28(1):17–23. doi:10.1002/(SICI)1097-0045(199601)28:1<17:AID-PROS3>3.0.CO;2-L

    Article  PubMed  CAS  Google Scholar 

  5. Roberts RO, Bergstralh EJ, Farmer SA, Jacobson DJ, Hebbring SJ, Cunningham JM, Thibodeau SN, Lieber MM, Jacobsen SJ (2006) Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia. Prostate 66(4):392–404. doi:10.1002/pros.20362

    Article  PubMed  CAS  Google Scholar 

  6. Ricke WA, McPherson SJ, Bianco JJ, Cunha GR, Wang Y, Risbridger GP (2008) Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling. FASEB J 22(5):1512–1520. doi:10.1096/fj.07-9526com

    Article  PubMed  CAS  Google Scholar 

  7. Ellem SJ, Risbridger GP (2009) The dual, opposing roles of estrogen in the prostate. Ann NY Acad Sci 1155:174–186. doi:10.1111/j.1749-6632.2009.04360.x

    Article  PubMed  CAS  Google Scholar 

  8. Royuela M, de Miguel MP, Bethencourt FR, Sanchez-Chapado M, Fraile B, Arenas MI, Paniagua R (2001) Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate. J Endocrinol 168(3):447–454. doi:10.1677/joe.0.1680447

    Article  PubMed  CAS  Google Scholar 

  9. DuSell CD, Umetani M, Shaul PW, Mangelsdorf DJ, McDonnell DP (2008) 27-Hydroxycholesterol is an endogenous selective estrogen receptor modulator. Mol Endocrinol 22(1):65–77. doi:10.1210/me.2007-0383

    Article  PubMed  CAS  Google Scholar 

  10. Wong SY, Lau WW, Leung PC, Leung JC, Woo J (2007) The association between isoflavone and lower urinary tract symptoms in elderly men. Br J Nutr 98(6):1237–1242. doi:10.1017/S0007114507787433

    Article  PubMed  CAS  Google Scholar 

  11. Brossner C, Petritsch K, Fink K, Auprich M, Madersbacher S, Adlercreutz H, Rehak P, Petritsch P (2004) Phytoestrogen tissue levels in benign prostatic hyperplasia and prostate cancer and their association with prostatic diseases. Urology 64(4):707–711. doi:10.1016/j.urology.2004.04.046

    Article  PubMed  Google Scholar 

  12. King CD, Rios GR, Green MD, Tephly TR (2000) UDP-glucuronosyltransferases. Curr Drug Metab 1(2):143–161

    Article  PubMed  CAS  Google Scholar 

  13. Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Belanger A, Fournel-Gigleux S, Green M, Hum DW, Iyanagi T, Lancet D, Louisot P, Magdalou J, Chowdhury JR, Ritter JK, Schachter H, Tephly TR, Tipton KF, Nebert DW (1997) The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 7(4):255–269

    Article  PubMed  CAS  Google Scholar 

  14. Vallee M, Albert C, Beaudry G, Hum DW, Belanger A (2001) Isolation and characterization of the monkey UDP-glucuronosyltransferase cDNA clone monUGT1A01 active on bilirubin and estrogens. J Steroid Biochem Mol Biol 77(4–5):239–249. doi:10.1016/S0960-0760(01)00062-0

    Article  PubMed  CAS  Google Scholar 

  15. Yong M, Schwartz SM, Atkinson C, Makar KW, Thomas SS, Stanczyk FZ, Westerlind KC, Newton KM, Holt VL, Leisenring WM, Lampe JW (2011) Associations between polymorphisms in glucuronidation and sulfation enzymes and sex steroid concentrations in premenopausal women in the United States. J Steroid Biochem Mol Biol 124(1–2):10–18. doi:10.1016/j.jsbmb.2010.12.014

    Article  PubMed  CAS  Google Scholar 

  16. Beutler E, Gelbart T, Demina A (1998) Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci USA 95(14):8170–8174

    Article  PubMed  CAS  Google Scholar 

  17. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, Lindhout D, Tytgat GN, Jansen PL, Oude Elferink RP et al (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 333(18):1171–1175. doi:10.1056/NEJM199511023331802

    Article  PubMed  CAS  Google Scholar 

  18. Barry MJ, Fowler FJ Jr, O’Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, Cockett AT et al (1992) The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol 148(5):1549–1557 discussion 1564

    PubMed  CAS  Google Scholar 

  19. Brossner C, Bayer G, Madersbacher S, Kuber W, Klingler C, Pycha A (2000) Twelve prostate biopsies detect significant cancer volumes (>0.5 mL). BJU Int 85(6):705–707. doi:10.1046/j.1464-410x.2000.00558.x

    Article  PubMed  CAS  Google Scholar 

  20. Albert C, Barbier O, Vallee M, Beaudry G, Belanger A, Hum DW (2000) Distribution of uridine diphosphate-glucuronosyltransferase (UGT) expression and activity in cynomolgus monkey tissues: evidence for differential expression of steroid-conjugating UGT enzymes in steroid target tissues. Endocrinology 141(7):2472–2480

    Article  PubMed  CAS  Google Scholar 

  21. Hajdinjak T, Zagradisnik B (2004) Prostate cancer and polymorphism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: frequency of DD homozygotes increases with Gleason Score. Prostate 59(4):436–439. doi:10.1002/pros.20024

    Article  PubMed  CAS  Google Scholar 

  22. Park J, Chen L, Shade K, Lazarus P, Seigne J, Patterson S, Helal M, Pow-Sang J (2004) Asp85tyr polymorphism in the udp-glucuronosyltransferase (UGT) 2B15 gene and the risk of prostate cancer. J Urol 171(6 Pt 1):2484–2488. doi:10.1097/01.ju.0000117748.44313.43

    Article  PubMed  CAS  Google Scholar 

  23. Park JY, Tanner JP, Sellers TA, Huang Y, Stevens CK, Dossett N, Shankar RA, Zachariah B, Heysek R, Pow-Sang J (2007) Association between polymorphisms in HSD3B1 and UGT2B17 and prostate cancer risk. Urology 70(2):374–379. doi:10.1016/j.urology.2007.03.001

    Article  PubMed  Google Scholar 

  24. Karypidis AH, Olsson M, Andersson SO, Rane A, Ekstrom L (2008) Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate. Pharmacogenomics J 8(2):147–151. doi:10.1038/sj.tpj.6500449

    Article  PubMed  CAS  Google Scholar 

  25. Olsson M, Lindstrom S, Haggkvist B, Adami HO, Balter K, Stattin P, Ask B, Rane A, Ekstrom L, Gronberg H (2008) The UGT2B17 gene deletion is not associated with prostate cancer risk. Prostate 68(5):571–575. doi:10.1002/pros.20700

    Article  PubMed  CAS  Google Scholar 

  26. Gsur A, Preyer M, Haidinger G, Schatzl G, Madersbacher S, Marberger M, Vutuc C, Micksche M (2002) A polymorphism in the UDP-Glucuronosyltransferase 2B15 gene (D85Y) is not associated with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 11(5):497–498

    PubMed  CAS  Google Scholar 

  27. Karatzas A, Giannatou E, Tzortzis V, Gravas S, Aravantinos E, Moutzouris G, Melekos M, Tsezou A (2010) Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men. Cancer Epidemiol 34(3):345–349. doi:10.1016/j.canep.2010.02.009

    Article  PubMed  Google Scholar 

  28. Tang L, Yao S, Till C, Goodman PJ, Tangen CM, Wu Y, Kristal AR, Platz EA, Neuhouser ML, Stanczyk FZ, Reichardt JK, Santella RM, Hsing A, Hoque A, Lippman SM, Thompson IM, Ambrosone CB (2011) Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Carcinogenesis 32(10):1500–1506. doi:10.1093/carcin/bgr139

    Article  PubMed  CAS  Google Scholar 

  29. Zintzaras E, Lau J (2008) Trends in meta-analysis of genetic association studies. J Hum Genet 53(1):1–9. doi:10.1007/s10038-007-0223-5

    Article  PubMed  CAS  Google Scholar 

  30. Zintzaras E, Lau J (2008) Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. J Clin Epidemiol 61(7):634–645. doi:10.1016/j.jclinepi.2007.12.011

    Article  PubMed  Google Scholar 

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Karatzas, A., Tzortzis, V., Giannatou, E. et al. Lack of association between the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphism and the risk of benign prostatic hyperplasia in Caucasian men. Mol Biol Rep 40, 6665–6669 (2013). https://doi.org/10.1007/s11033-013-2781-2

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  • DOI: https://doi.org/10.1007/s11033-013-2781-2

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