SRD5A2 Gene Polymorphisms and the Risk of Benign Prostatic Hyperplasia but not Prostate Cancer

  • Published : 2015.03.04


Background: Testosterone, a primary androgen in males, is converted into its most active form, dihydrotestosterone (DHT), by $5{\alpha}$-reductase type 2 (encoded by the SRD5A2 gene) in the prostate. DHT is necessary for prostatic growth and has five times higher binding affinity than testosterone for androgen receptors. We hypothesized that polymorphic variations in the SRD5A2 gene may affect the risk of benign prostatic hyperplasia and prostate cancer. Materials and Methods: We analyzed SRD5A2 gene polymorphisms in 217 BPH patients, 192 PCa cases, and 171 controls. Genotyping was undertaken using direct DNA sequencing. Genotype data were compared between cases and controls using a Chi square statistical tool. Results: We found that the A49T locus was monomorphic with 'AA' genotype in all subjects. At V89L locus, the presence of 'VV' showed a marginally significant correlation with increased BPH risk (p=0.047). At the $(TA)_n$ locus, longer TA repeats were found to be protective against BPH (p=0.003). However, neither of these polymoprhisms correlated with the risk of PCa. Conclusions: We conclude that A49T is monomorphic in the study population, VV marginally correlates with BPH risk, and longer $(TA)_n$ repeats are protective against BPH. None of these polymorphisms affect the risk of PCa.


Supported by : Indian Council of Medical Research (ICMR)


  1. Allen NE, Forrest MS, Key TJ (2001). The association between polymorphisms in the CYP17 and 5$\alpha$-reductase (SRD5A2) genes and serum androgen concentrations in men. Cancer Epidemiol Biomarkers Prev, 10, 185-9.
  2. Andersson S, Russell DW (1990). Structural and biochemical properties of cloned and expressed human and rat steroid 5-alpha-reductases. Proc Natl Acad Sci USA, 87, 3640-4.
  3. Berry SJ, Coffey DS, Walsh PC, Ewing LL (1984). The development of human benign prostatic hyperplasia with age. J Urol, 132, 474-9.
  4. Boyle P, Napalkov P (1996). Epidemiology of benign prostatic hyperplasia: current perspectives. Urology, 2, 7-11.
  5. Das K, Peh YC, Pei LL. et al (2008). Shorter CAG repeats in androgen receptor and non-GG genotypes in prostatespecific antigen loci are associated with decease risk of benign prostatic hyperplasia and prostate cancer. Cancer Letters, 268, 340-7.
  6. El Ezzi AA, Zaidan WR, El-Saidi MA, et al (2014). Association of benign prostate hyperplasia with polymorphisms in VDR, CYP17, and SRD5A2 genes among Lebanese men. Asian Pac J Cancer Prev, 15, 1255-62.
  7. Feigelson HS, Ross RK, Yu MC et al (1996). Genetic susceptibility to cancer from exogenous and endogenous exposures. J Cell Biochem, 25, 15-22.
  8. Heinlein CA, Chang C (2004). Androgen receptor in prostate cancer. Endocr Rev, 25, 276-308.
  9. Imperato-Mc G J, Peterson RE, Gautier T, Sturla E (1979). Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5-alpha-reductase deficiency. N Engl J Med, 300, 1233-7.
  10. Isaacs JT (1994). Etiology of benign prostatic hyperplasia. Eur Urol, 25, 6-9.
  11. Izmirli M, Arikan B, Bayazit Y, Alptekin D (2011). Associations of polymorphisms in HPC2/ELAC2 and SRD5A2 genes with benign prostate hyperplasia in Turkish men. Asian Pac J Cancer Prev, 12, 731-3.
  12. Jamal K, Patel P, Sooriakumaran P (2008). Minimally invasive surgical modalities in the management of localized prostate cancer. Expert Rev Anticancer Ther, 8, 957-66.
  13. Jun L, Ralph J, Coates MG (2010). Steroid $5{\alpha}$-reductase type 2 ($SRD5{\alpha}2$) gene polymorphisms and risk of prostate cancer: a huge review. Am J Epidemiology, 171, 1-13.
  14. Li X, Huang Y, Fu X, et al (2011). Meta-analysis of three polymorphisms in the steroid-5-alpha-reductase, alpha polypeptide 2 gene (SRD5A2) and risk of prostate cancer. Mutagenesis, 26, 371-83.
  15. Makridakis NM, Ross RK, Pike MC, et al (1999). Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA. Lancet, 354, 975-8.
  16. Makridakis N, Ross RK, Pike MC, et al (1997). A prevalent missense substitution that modulates activity of prostatic steroid 5-alpha-reductase. Cancer Res, 57, 1020-22.
  17. Makridakis NM, di Salle E, Reichardt JK (2000). Biochemical and pharmacogenetic dissection of human steroid 5 alphareductase type II. Pharmacogenetics, 10, 407-13.
  18. Mohammad TS, Giske U, Eila CS, et al (2005). Association between polymorphisms in the steroid 5-$\alpha$ reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer. Urologic Oncology, 23, 246-53.
  19. Petitti DB (2001). Approaches to heterogeneity in meta-analysis. Stat Med, 20, 3625-33.
  20. Reichardt JK, Makridakis N, Henderson Be, et al (1995). Genetic variability of the human SRD5A2 gene: implication for prostate cancer risk. Cancer Res, 55, 3973-75.
  21. Ross RK, Bernstein L, Lobo RA, et al (1992). 5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet, 339, 887-9.
  22. Salman MT, Ursin G, Skinner EC, Dessissa T, Reichardt JK (2005). Associations between polymorphisms in the steroid 5-alpha reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer. Urol Oncol, 23, 246-53.
  23. Singh R, Krishnaswamy V, Singh P, et al (2009). Longer (TA)n repeats but not A49T and V89L polymorphisms in SRD5A2 gene may confer prostate cancer risk in south Indian men. J Androl, 30, 703-10.
  24. Sobti RC, Gupta L, Singh SK, et al (2008). Role of hormonal genes and risk of prostate cancer: gene-gene interactions in a North Indian population. Cancer Genetics Cytogenetics, 185, 78-85.
  25. Srinivas V, Mehta H, Amin A, et al (1995). Carcinoma of the prostate-state at initial presentation. Int Urol Nephrol, 27, 419-22.
  26. Stanford JL, Just JJ, Gibbs M, et al (1997). Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res, 57, 1194-98.
  27. Suzuki T, Darnel AD, Akahira JI, et al (2001). 5-alfa-reductase in human breast carcinoma: possible modulator of in situ androgenic actions. J Clin Endocrinol Metab, 86, 250-57.
  28. Thangaraj K, Singh L, Reddy AG, et al (2003). Genetic affinities of the Andaman Islanders, a vanishing human population. Curr Biol, 13, 86-93.
  29. Thigpen AE, Davis DL, Milatovich A, et al (1992). Molecular genetics of steroid 5-alpha-reductase 2 eficiency. J Clin Invest, 90, 799-09.
  30. Wilbert DM, Griffin JE, Wilson JD (2008). Characterization of the cytosol androgen receptor of the human prostate. J Clin Endocrinol Metab, 56, 113-20.
  31. Wilson JD, Griffin JE, Russell DW (1993). Steroid 5-alphareductase 2 deficiency. Endocr Rev, 14, 577-93.
  32. Wilson JD, Griffin JE, Russell DW (1993). Steroid 5-alphareductase 2 deficiency. Endocr Rev, 14, 577-93.
  33. Zhenhua LI, Tomonori H, Kenji M, et al (2003). Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population. J Urology, 169, 2378-81.

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