Portal de Periódicos da CAPES

Association Among an Ornithine Decarboxylase Polymorphism, Androgen Receptor Gene (CAG) Repeat Length and Prostate Cancer Risk

2004; Lippincott Williams & Wilkins; Volume: 171; Issue: 2 Linguagem: Inglês

10.1097/01.ju.0000108384.74718.73

1527-3792

Kala Visvanathan, Kathy J. Helzlsouer, David W. Boorman, Paul T. Strickland, Sandy Hoffman, George W. Comstock, Thomas G. O’Brien, Yongjun Guo,

Hormonal and reproductive studies

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 Feb 2004Association Among an Ornithine Decarboxylase Polymorphism, Androgen Receptor Gene (CAG) Repeat Length and Prostate Cancer Risk KALA VISVANATHAN, KATHY J. HELZLSOUER, DAVID W. BOORMAN, PAUL T. STRICKLAND, SANDY C. HOFFMAN, GEORGE W. COMSTOCK, THOMAS G. O'BRIEN, and YONGJUN GUO KALA VISVANATHANKALA VISVANATHAN , KATHY J. HELZLSOUERKATHY J. HELZLSOUER , DAVID W. BOORMANDAVID W. BOORMAN , PAUL T. STRICKLANDPAUL T. STRICKLAND , SANDY C. HOFFMANSANDY C. HOFFMAN , GEORGE W. COMSTOCKGEORGE W. COMSTOCK , THOMAS G. O'BRIENTHOMAS G. O'BRIEN , and YONGJUN GUOYONGJUN GUO View All Author Informationhttps://doi.org/10.1097/01.ju.0000108384.74718.73AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: A single nucleotide substitution of guanine to adenine (A) at base +316 in the ornithine decarboxylase (ODC) gene may be associated with greater ODC expression and increased tumor growth. ODC is induced by androgens in human prostatic epithelial cells, presumably via transcriptional activation of androgen receptor (AR) and also by nicotine. A nested case-control study was done to examine the association between this ODC genotype and prostate cancer risk, and whether it varies by AR gene CAG repeat length and smoking. Materials and Methods: A total of 164 cases were matched to 2 controls each from a community based cohort. ODC and AR genotyping was performed using a TaqMan (PE Applied Biosystems, Foster City, California) based assay and automated fragment analysis, respectively. Conditional logistic regression was used to estimate the OR and 95% CI. Results: The presence of the ODC A allele was not significantly associated with an increased risk of prostate cancer (OR 1.33, 95% CI 0.90 to 1.96). However, men who inherited at least 1 ODC A alleles and less than 22 AR CAG repeats were at twice the risk of prostate cancer compared with those with 2 guanine alleles and 22 or greater AR CAG repeats (OR 2.09, 95% CI 1.23 to 3.57). Smoking was associated with prostate cancer only in men carrying a least 1 ODC A allele (p interaction = 0.02). Conclusions: The ODC A allele was not associated with a statistically significant increased risk of prostate cancer. However, this association may vary according to the number of CAG repeats in the AR receptor and smoking status. References 1 : Polyamines in rapid growth and cancer. Biochim Biophys Acta1978; 473: 241. Google Scholar 2 : Ornithine decarboxylase over expression is a sufficient condition for tumor promotion in mouse skin. Cancer Res1997; 57: 2630. Google Scholar 3 : Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans. Clin Cancer Res1999; 5: 143. Google Scholar 4 : Chemoprevention of prostate carcinogenesis by alpha-difluoromethylornithine in TRAMP mice. Cancer Res2000; 60: 5125. Google Scholar 5 : Functional analysis of human ornithine decarboxylase alleles. Cancer Res2000; 60: 6314. Google Scholar 6 : Androgen regulation of ornithine decarboxylase in human prostatic cells identified using differential display. FEBS Lett1997; 405: 328. Google Scholar 7 : Androgen-regulation of ornithine decarboxylase and S-adenosylmethionine decarboxylase genes. J Steroid Biochem Mol Biol1991; 40: 307. Google Scholar 8 : Androgen-induced cell growth and c-myc expression in human non-transformed epithelial prostatic cells in primary culture. Endocr Res2001; 27: 153. Google Scholar 9 : The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res1994; 22: 3181. Crossref, Medline, Google Scholar 10 : Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J Mol Endocrinol2000; 25: 85. Google Scholar 11 : Is the androgen receptor CAG repeat length significant for prostate cancer?. Cancer Epidemiol Biomarkers Prev2002; 11: 985. Google Scholar 12 : Androgen receptor CAG repeats and prostate cancer. Am J Epidemiol2002; 155: 883. Google Scholar 13 : K6/ODC transgenic mice as a sensitive model for carcinogen identification. Toxicol Lett2000; 116: 27. Google Scholar 14 : Effect of nicotine and N′-nitrosonornicotine on rat lung and trachea ornithine decarboxylase activity. Carcinogenesis1985; 6: 1517. Google Scholar 15 : Tobacco smoking and prostate cancer: time for an appraisal. Ann Oncol2001; 12: 733. Google Scholar 16 : AJCC Cancer Staging Manual. Philadelphia: Lippincott-Raven Publishers1997. Google Scholar 17 : Automated fragment analysis method for determining androgen receptor CAG repeat length. Biotechniques2002; 33: 140. Google Scholar 18 : Cigarette smoking and serum sex hormones in men. Am J Epidemiol1988; 128: 796. Google Scholar 19 : Cigarette smoke-induced DNA damage and lung cancer risk. Nature1980; 283: 388. Google Scholar 20 : Uptake and secretion of carcinogenic chemicals by the dog and rat prostate. In: The Prostate Cell: Structure and Function. Edited by . New York: Alan R. Liss1981: 131. Google Scholar From the Johns Hopkins Bloomberg School of Public Health (KV, KJH, PS, SH, GC), Baltimore, Maryland, and Lankenau Institute for Medical Research (DB, TGO'B, YG), Wynnewood, Pennsylvania© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 171Issue 2February 2004Page: 652-655 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsornithine decarboxylaseprostateprostatic neoplasmspolymorphism (genetics)receptors, androgenMetricsAuthor Information KALA VISVANATHAN More articles by this author KATHY J. HELZLSOUER More articles by this author DAVID W. BOORMAN More articles by this author PAUL T. STRICKLAND More articles by this author SANDY C. HOFFMAN More articles by this author GEORGE W. COMSTOCK More articles by this author THOMAS G. O'BRIEN More articles by this author YONGJUN GUO More articles by this author Expand All Advertisement PDF downloadLoading ...