OJPM  Vol.3 No.4 , July 2013
UGT2B17 status and risk of prostate cancer: A meta-analysis
ABSTRACT

Objective: Recent studies on the association between Uridine diphosphoglucuronosyl tranferases (UGT) 2B17 status and risk of prostate cancer (PCa) showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies. Methods: We searched published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI). According to our inclusion criteria, studies that observed the association between UGT2B17 status and PCa risk were included. The principal outcome measure was the adjusted odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with UGT2B17 status. Results: A total of 6 studies with 7029 subjects (3839 cases and 3190 controls) were eligible for inclusion in the meta-analysis. Overall, there was a significant association between UGT2B17 status and increased risk of prostate cancer (OR = 1.74, 95% CI 1.14 - 2.64, P < 0.001). Similar results were found in the subgroup analyses by ethnicity and types of controls. Conclusion: This meta-analysis demonstrates that UGT2B17 status is associated with prostate cancer susceptibility, and it contributes to increased risk of prostate cancer.


Cite this paper
Kpoghomou, M. , Kalembo, F. , Soatiana, J. , Bishwajit, G. and Sheng, W. (2013) UGT2B17 status and risk of prostate cancer: A meta-analysis. Open Journal of Preventive Medicine, 3, 329-337. doi: 10.4236/ojpm.2013.34044.
References
[1]   Potter, J.D. (1997) Food, nutrition and the prevention of cancer: A global perspective. American Institute for Cancer Research.

[2]   Damber, J.E. and Aus, G. (2008) Prostate cancer. Lancet, 371, 1710-1721. doi:10.1016/S0140-6736(08)60729-1

[3]   Cardon, L.R., et al. (2008) Genetic susceptibility to cancer: The role of polymorphisms in candidate genes. JAMA, 299, 2423-2436. doi:10.1001/jama.299.20.2423

[4]   Gronberg, H. (2003) Prostate cancer epidemiology. Lancet, 361, 859-864. doi:10.1016/S0140-6736(03)12713-4

[5]   Lipsett, M.B. (1977) Estrogen use and cancer risk. Journal of the American Medical Informatics Association, 237, 1112-1115. doi:10.1001/jama.1977.03270380056020

[6]   Denis, L. and Mahler, C. (1990) Prostatic cancer. An overview. Acta Oncologica, 29, 665-677. doi:10.3109/02841869009090072

[7]   Hsing, A.W. and Chokkalingam, A.P. (2006) Prostate cancer epidemiology. Frontiers in Bioscience, 11, 1388-1413. doi:10.2741/1891

[8]   Belanger, G., Beaulieu, M., Marcotte, B., et al. (1995) Expression of transcripts encoding steroid UDP-glucuronosyltransferases in human prostate hyperplastic tissue and the LNCaP cell line. Molecular and Cellular Endocrinology, 113, 165-173. doi:10.1016/0303-7207(95)03627-J

[9]   Ross, R., Bernstein, L., Judd, H., et al. (1986) Serum testosterone levels in healthy young black and white men. Journal of the National Cancer Institute, 76, 45-48.

[10]   Hajdinjak, T. and Zagradisnik, B. (2004) Prostate cancer and polymor-phism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: Frequency of DD homozygotes increases with Glasgow Score. Prostate, 59, 436439. doi:10.1002/pros.20024

[11]   Gsur, A., Preyer, M., Haidinger, G., et al. (2002) A polymorphism in the UDP-glucuronosyltransferase 2B15 gene (D85Y) is not associated with prostate cancer risk. Cancer Epidemiology, Biomarkers & Prevention, 11, 497-498.

[12]   Park, J., Chen, L., Shade, K., et al. (2004) Asp85tyr polymorphism in the UDP-glucuronosyltransferase (UGT) 2B15 gene and the risk of prostate cancer. Journal of Urology, 171, 2484-2488. doi:10.1097/01.ju.0000117748.44313.43

[13]   Park, J., Chen, L., Ratnashinge, L., et al. (2006) Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate cancer in African American and Caucasian men. Cancer Epidemiology, Biomarkers & Prevention, 15, 1473-1478. doi:10.1158/1055-9965.EPI-06-0141

[14]   Hsing, A.W. (2001) Hormones and prostate cancer: What’s next? Epidemiologic Reviews, 23, 42-58. doi:10.1093/oxfordjournals.epirev.a000795

[15]   Ross, R.K., Bernstein, L., Lobo, R.A., Shimizu, H., Stanczyk, F.Z., Pike, M.C., et al. (1992) 5-Alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet, 339, 887-889. doi:10.1016/0140-6736(92)90927-U

[16]   Lookingbill, D.P., Demers, L.M., Wang, C., Leung, A., Rittmaster, R.S. and Santen, R.J. (1991) Clinical and biochemical parameters of androgen action in normal healthy Caucasian versus Chinese subjects. The Journal of Clinical Endocrinology & Metabolism, 72, 1242-1248. doi:10.1210/jcem-72-6-1242

[17]   Whittemore, A.S., Kolonel, L.N., Wu, A.H., John, E.M., Gallagher, R.P., Howe, G.R., et al. (1995) Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. Journal of the National Cancer Institute, 87, 652661. doi:10.1093/jnci/87.9.652

[18]   Hum, D.W., Belanger, A., Levesque, E., Barbier, O., Beaulieu, M., Albert, C., et al. (1999) Characterization of UDP-glucuronosyltransferases active on steroid hormones. The Journal of Steroid Biochemistry and Molecular Biology, 69, 413-423. doi:10.1016/S0960-0760(99)00061-8

[19]   Barbier, O., Lapointe, H., El Alfy, M., Hum, D.W. and Belanger, A. (2000) Cellular localization of uridine diphosphoglucuronosyltransferase 2B enzymes in the human prostate by in situ hybridization and immunohistochemistry. The Journal of Clinical Endocrinology & Metabolism, 85, 4819-4826. doi:10.1210/jc.85.12.4819

[20]   Turgeon, D., Carrier, J.S., Levesque, E., Hum, D.W. and Belanger, A. (2001) Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members. Endocrinology, 142, 778-787. doi:10.1210/en.142.2.778

[21]   Wilson III, W., de Villena, F.P.-M., Lyn-Cook, B.D., Chatterjee, P.K., Bell, T.A., Detwiler, D.A., et al. (2004) Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15. Genomics, 84, 707-714. doi:10.1016/j.ygeno.2004.06.011

[22]   Murata, M., Warren, E.H. and Riddell, S.R. (2003) A human minor histocompatibility antigen resulting from differential expression due to a gene deletion. The Journal of Experimental Medicine, 197, 1279-1289. doi:10.1084/jem.20030044

[23]   Setlur, S.R., Chen, C.X., Hossain, R.R., et al. (2010) Genetic variation of genes involved in dihydrotestosterone metabolism and the risk of prostate cancer. Cancer Epidemiology, Biomarkers & Prevention, 19, 229-239. doi:10.1158/1055-9965.EPI-09-1018

[24]   Karypidis, A.-H., Olsson, M., Andersson, S.-O., Rane, A. and 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. The Pharmacogenomics Journal, 8, 147-151. doi:10.1038/sj.tpj.6500449

[25]   Olsson, M., Lindstrom, S., Haggkvist, B., Adami, H.-O., et al. (2008) The UGT2B17 gene deletion is not associated with prostate cancer risk. The Prostate, 68, 571-575. doi:10.1002/pros.20700

[26]   Gallagher, C.J., Kadlubar, F.F., et al. (2007) The UGT2B17 gene deletion polymorphism and risk of prostate cancer. A case-control study in Caucasians. Cancer Detection and Prevention Journal, 31, 310-315. doi:10.1016/j.cdp.2007.07.005

[27]   Park, J.Y., Tanner, J.-P., Sellers, T.A., et al. (2007) Association between polymorphisms in HSD3B1 and UGT2B17 and prostate cancer risk. Urology, 70, 374-379. doi:10.1016/j.urology.2007.03.001

[28]   Park, J., Chen, L., Ratnashinge, L., et al. (2006) Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate cancer in African American and Caucasian men. Cancer Epidemiology, Biomarkers & Prevention, 15, 1473-1478. doi:10.1158/1055-9965.EPI-06-0141

[29]   Mantel, N. and Haenszel, W. (1959) Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute, 22, 719-748.

[30]   DerSimonian, R. and Laird, N. (1986) Meta-analysis in clinical trials. Controlled Clinical Trials, 7, 177-188. doi:10.1016/0197-2456(86)90046-2

[31]   Cochran, W.G. (1954) The combination of estimates from different experiments. Biometrics, 10, 101-129. doi:10.2307/3001666

[32]   Higgins, J.P., Thompson, S.G., Deeks, J.J. and Altman, D.G. (2003) Measuring inconsistency in meta-analyses. BMJ, 327, 557-560. doi:10.1136/bmj.327.7414.557

[33]   Egger, M., Davey Smith, G., Schneider, M. and Minder, C. (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-634. doi:10.1136/bmj.315.7109.629

[34]   Nadeau, G., et al. (2011) Deletions of the androgen-metabolizing UGT2B genes have an effect on circulating steroid levels and biochemical recurrence after radical prostatectomy in localized prostate cancer. The Journal of Clinical Endocrinology & Metabolism, 96, E1550-E1557. doi:10.1210/jc.2011-1049

[35]   Menard, V., et al. (2009) Copy-number variations (CNVs) of the human sex steroid metabolizing genes UGT2B17 and UGT2B28 and their associations with a UGT2B15 functional polymorphism. Human Mutation, 30, 13101319. doi:10.1002/humu.21054

[36]   Hu, D.G., et al. (2010) A novel polymorphism in a forkhead box A1 (FOXA1) binding site of the human UDP glucuronosyltransferase 2B17 gene modulates promoter activity and is associated with altered levels of circulating androstane-3α, 17β-diol glucuronide. Molecular Pharmacology, 78, 714-722. doi:10.1124/mol.110.065953

[37]   Dong, L.M., Potter, J.D., White, E., Ulrich, C.M., Cardon, L.R., et al. (2008) Genetic susceptibility to cancer: The role of polymorphisms in candidate genes. JAMA, 299, 2423-2436. doi:10.1001/jama.299.20.2423

[38]   Chouinard, S., Pelletier, G., Belanger, A. and Barbier, O. (2004) Cellular specific expression of the androgen-conjugating enzymes UGT2B15 and UGT2B17 in the human prostate epithelium. Endocrine Research, 30, 717-725. doi:10.1081/ERC-200044014

[39]   Green, M.D. and Tephly, T.R. (1996) Glucuronidation of amines and hydroxylated xenobiotics and endobiotics catalyzed by expressed human UGT1.4 protein. Drug Metabolism and Disposition, 24, 356-363.

[40]   Gann, P.H., Hennekens, C.H., Ma, J., Longcope, C. and Stampfer, M.J. (1996) Prospective study of sex hormone levels and risk of prostate cancer. Journal of the National Cancer Institute, 88, 1118-1126. doi:10.1093/jnci/88.16.1118

[41]   Cai, L., Huang, W. and Chou, K.C. (2012) Prostate cancer with variants in CYP17 and UGT2B17 genes: A metaanalysis. Protein & Peptide Letters, 19, 62. doi:10.2174/092986612798472848

[42]   Jakobsson, J., Ekstrom, L., Inotsume, N., Garle, M., Lorentzon, M., Ohlsson, C., et al. (2006) Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. The Journal of Clinical Endocrinology & Metabolism, 91, 687-693. doi:10.1210/jc.2005-1643

 
 
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