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. 2001 May;84(10):1344–1347. doi: 10.1054/bjoc.2001.1789

A missense substitution A49T in the steroid 5-alpha-reductase gene (SRD5A2) is not associated with prostate cancer in Finland

N Mononen 1, T Ikonen 1, K Syrjäkoski 1, M Matikainen 1, J Schleutker 1, T L J Tammela 2, P A Koivisto 1, O P Kallioniemi 1
PMCID: PMC2363646  PMID: 11355945

Abstract

Prostatic steroid 5-alpha-reductase gene (SRD5A2) encodes a critical enzyme involved in the conversion of testosterone to dihydrotestosterone. A germline mis-sense substitution (A49T) leads to a variant SRD5A2 protein, which has a 5-fold higher in vitro V max than the wild-type protein (Ross et al, 1998; Makridakis et al, 1999). The A49T variant was recently associated with 2.5 to 3.28-fold increased risk of prostate cancer (PC) in African-American and Hispanic men (Makridakis et al, 1999). Also, Jaffe et al (2000) reported an association between A49T and more aggressive disease among Caucasian patients. Here, we report that the prevalence of the A49T variant in 449 Finnish PC patients was 6.0%, not significantly different from 6.3% observed in 223 patients with benign prostatic hyperplasia or 5.8% in 588 population-based controls (odds ratio for PC 1.04, 95% C.I. 0.62–1.76 P = 0.89). There was no association between A49T and the family history of the patients nor with tumour stage or grade. Our results argue against a prominent role of the A49T variant as a genetic risk factor for prostate cancer development and progression in the Finnish population. © 2001 Cancer Research Campaign www.bjcancer.com

Keywords: prostate cancer, 5-alpha-reductase, A49T, mutation

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Selected References

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  1. Berry R., Schroeder J. J., French A. J., McDonnell S. K., Peterson B. J., Cunningham J. M., Thibodeau S. N., Schaid D. J. Evidence for a prostate cancer-susceptibility locus on chromosome 20. Am J Hum Genet. 2000 May 16;67(1):82–91. doi: 10.1086/302994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berthon P., Valeri A., Cohen-Akenine A., Drelon E., Paiss T., Wöhr G., Latil A., Millasseau P., Mellah I., Cohen N. Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2-43. Am J Hum Genet. 1998 Jun;62(6):1416–1424. doi: 10.1086/301879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cunha G. R., Donjacour A. A., Cooke P. S., Mee S., Bigsby R. M., Higgins S. J., Sugimura Y. The endocrinology and developmental biology of the prostate. Endocr Rev. 1987 Aug;8(3):338–362. doi: 10.1210/edrv-8-3-338. [DOI] [PubMed] [Google Scholar]
  4. Davis D. L., Russell D. W. Unusual length polymorphism in human steroid 5 alpha-reductase type 2 gene (SRD5A2). Hum Mol Genet. 1993 Jun;2(6):820–820. doi: 10.1093/hmg/2.6.820. [DOI] [PubMed] [Google Scholar]
  5. Devgan S. A., Henderson B. E., Yu M. C., Shi C. Y., Pike M. C., Ross R. K., Reichardt J. K. Genetic variation of 3 beta-hydroxysteroid dehydrogenase type II in three racial/ethnic groups: implications for prostate cancer risk. Prostate. 1997 Sep 15;33(1):9–12. doi: 10.1002/(sici)1097-0045(19970915)33:1<9::aid-pros2>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  6. Febbo P. G., Kantoff P. W., Platz E. A., Casey D., Batter S., Giovannucci E., Hennekens C. H., Stampfer M. J. The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer. Cancer Res. 1999 Dec 1;59(23):5878–5881. [PubMed] [Google Scholar]
  7. Ford D., Easton D. F., Bishop D. T., Narod S. A., Goldgar D. E. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994 Mar 19;343(8899):692–695. doi: 10.1016/s0140-6736(94)91578-4. [DOI] [PubMed] [Google Scholar]
  8. Friedman L. S., Szabo C. I., Ostermeyer E. A., Dowd P., Butler L., Park T., Lee M. K., Goode E. L., Rowell S. E., King M. C. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families. Am J Hum Genet. 1995 Dec;57(6):1284–1297. [PMC free article] [PubMed] [Google Scholar]
  9. Gibbs M., Stanford J. L., Jarvik G. P., Janer M., Badzioch M., Peters M. A., Goode E. L., Kolb S., Chakrabarti L., Shook M. A genomic scan of families with prostate cancer identifies multiple regions of interest. Am J Hum Genet. 2000 May 19;67(1):100–109. doi: 10.1086/302969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gibbs M., Stanford J. L., McIndoe R. A., Jarvik G. P., Kolb S., Goode E. L., Chakrabarti L., Schuster E. F., Buckley V. A., Miller E. L. Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. Am J Hum Genet. 1999 Mar;64(3):776–787. doi: 10.1086/302287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Giovannucci E., Stampfer M. J., Krithivas K., Brown M., Dahl D., Brufsky A., Talcott J., Hennekens C. H., Kantoff P. W. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3320–3323. doi: 10.1073/pnas.94.7.3320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ingles S. A., Ross R. K., Yu M. C., Irvine R. A., La Pera G., Haile R. W., Coetzee G. A. Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst. 1997 Jan 15;89(2):166–170. doi: 10.1093/jnci/89.2.166. [DOI] [PubMed] [Google Scholar]
  13. Irvine R. A., Yu M. C., Ross R. K., Coetzee G. A. The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. Cancer Res. 1995 May 1;55(9):1937–1940. [PubMed] [Google Scholar]
  14. Jaffe J. M., Malkowicz S. B., Walker A. H., MacBride S., Peschel R., Tomaszewski J., Van Arsdalen K., Wein A. J., Rebbeck T. R. Association of SRD5A2 genotype and pathological characteristics of prostate tumors. Cancer Res. 2000 Mar 15;60(6):1626–1630. [PubMed] [Google Scholar]
  15. Kantoff P. W., Febbo P. G., Giovannucci E., Krithivas K., Dahl D. M., Chang G., Hennekens C. H., Brown M., Stampfer M. J. A polymorphism of the 5 alpha-reductase gene and its association with prostate cancer: a case-control analysis. Cancer Epidemiol Biomarkers Prev. 1997 Mar;6(3):189–192. [PubMed] [Google Scholar]
  16. Lunn R. M., Bell D. A., Mohler J. L., Taylor J. A. Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2). Carcinogenesis. 1999 Sep;20(9):1727–1731. doi: 10.1093/carcin/20.9.1727. [DOI] [PubMed] [Google Scholar]
  17. Makridakis N. M., Ross R. K., Pike M. C., Crocitto L. E., Kolonel L. N., Pearce C. L., Henderson B. E., Reichardt J. K. Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA. Lancet. 1999 Sep 18;354(9183):975–978. doi: 10.1016/S0140-6736(98)11282-5. [DOI] [PubMed] [Google Scholar]
  18. Makridakis N., Ross R. K., Pike M. C., Chang L., Stanczyk F. Z., Kolonel L. N., Shi C. Y., Yu M. C., Henderson B. E., Reichardt J. K. A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase. Cancer Res. 1997 Mar 15;57(6):1020–1022. [PubMed] [Google Scholar]
  19. Peltonen L. Molecular background of the Finnish disease heritage. Ann Med. 1997 Dec;29(6):553–556. doi: 10.3109/07853899709007481. [DOI] [PubMed] [Google Scholar]
  20. Reichardt J. K., Makridakis N., Henderson B. E., Yu M. C., Pike M. C., Ross R. K. Genetic variability of the human SRD5A2 gene: implications for prostate cancer risk. Cancer Res. 1995 Sep 15;55(18):3973–3975. [PubMed] [Google Scholar]
  21. Ross R. K., Pike M. C., Coetzee G. A., Reichardt J. K., Yu M. C., Feigelson H., Stanczyk F. Z., Kolonel L. N., Henderson B. E. Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Res. 1998 Oct 15;58(20):4497–4504. [PubMed] [Google Scholar]
  22. Smith J. R., Freije D., Carpten J. D., Grönberg H., Xu J., Isaacs S. D., Brownstein M. J., Bova G. S., Guo H., Bujnovszky P. Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search. Science. 1996 Nov 22;274(5291):1371–1374. doi: 10.1126/science.274.5291.1371. [DOI] [PubMed] [Google Scholar]
  23. Suarez B. K., Lin J., Burmester J. K., Broman K. W., Weber J. L., Banerjee T. K., Goddard K. A., Witte J. S., Elston R. C., Catalona W. J. A genome screen of multiplex sibships with prostate cancer. Am J Hum Genet. 2000 Mar;66(3):933–944. doi: 10.1086/302818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Syvänen A. C. Solid-phase minisequencing as a tool to detect DNA polymorphism. Methods Mol Biol. 1998;98:291–298. doi: 10.1385/0-89603-443-7:291. [DOI] [PubMed] [Google Scholar]
  25. Taylor J. A., Hirvonen A., Watson M., Pittman G., Mohler J. L., Bell D. A. Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res. 1996 Sep 15;56(18):4108–4110. [PubMed] [Google Scholar]
  26. Xu J., Meyers D., Freije D., Isaacs S., Wiley K., Nusskern D., Ewing C., Wilkens E., Bujnovszky P., Bova G. S. Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat Genet. 1998 Oct;20(2):175–179. doi: 10.1038/2477. [DOI] [PubMed] [Google Scholar]

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