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Androgen Receptor Polymorphisms and the Incidence of Prostate Cancer¹

Program in Epidemiology [C. C., N. L., N. S. W., D. A. D.], Cancer Prevention Program [M. B., G. G.], and Program in Biostatistics [R. E., D. D.], Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024; Departments of Biostatistics [R. E.] and Epidemiology [C. C., N. S. W.], University of Washington, Seattle, Washington, 98195; and Swedish Tumor Institute, Seattle, Washington 98104 [G. G.]

	Abstract

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The human androgen receptor gene contains polymorphic CAG and GGC repeats in exon 1. We investigated whether the number of CAG and/or GGC repeats is related to prostate cancer risk in a case-control study nested within the ß Carotene and Retinol Efficacy Trial. Among 300 cases and 300 controls, we did not observe any increase in risk associated with fewer CAG or GGC repeats. We observed a nonsignificant decrease in risk associated with each unit of decrease in CAG length [odds ratio (OR), 0.98; 95% confidence interval (CI), 0.93–1.03). Men with CAG <22 had a relative risk of prostate cancer of 0.89 (95% CI, 0.65–1.23) compared with men with CAG 22. There was no appreciable difference in the mean number of GGC repeats between cases and controls; the estimated change in the risk of prostate cancer associated with one fewer GGC repeat was 0.97 (95% CI, 0.88–1.06). The risk in men at or below the mean number of GGC repeats (17) was 0.80 (95% CI, 0.57–1.12). In contrast to prior reports, men with both short CAG (<22) and short GGC (17) repeats were not at increased risk of prostate cancer (OR, 0.56; 95% CI, 0.32–0.98), compared with men with 22 CAG repeats and >17 GGC repeats. Our results do not support the hypothesis that a small number of CAG or GGC repeats in the androgen receptor gene increases a man’s risk of prostate cancer.

	Introduction

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The growth and development of the human prostate gland, together with the maintenance of its physiological integrity, are dependent on the presence of circulating androgens and intact intracellular steroid signaling pathways (1) . Androgens are generally required for prostate cancer development (2) ; administration of high doses of testosterone has induced prostate cancer in rodents (3 , 4) , and prostate cancer rarely occurs in castrated men. Prostate cancers often regress after androgen withdrawal (5, 6, 7, 8) .

The AR³ gene is located on the X chromosome and spans more than 90 kb of genomic DNA (9) . The AR protein has three major domains: an androgen-binding domain, a DNA-binding domain, and the NH₂-terminal domain (modulatory domain; Refs. 10 , 11 ). Androgens, particularly dihydrotestosterone, bind to the AR with high affinity and stimulate the transcription of a cascade of androgen-responsive genes. The transactivation activity of the receptor resides in the NH₂-terminal domain of the protein, which is encoded in exon 1 and contains the polymorphic CAG and GGN repeats (12 , 13) . The CAG and GGC repeats encode for a polyglutamine tract and a polyglycine tract, respectively. In addition to stimulating expression of genes associated with the differentiated phenotype of the prostate, such as prostate-specific antigen (14) , it has been reported that AR may regulate genes involved in cell-cycle control, e.g., CDK2, CDK4, and p16 (15) . Extended polyglutamine tract interacts with caspase-8 and caspase-10 in nuclear aggregates (16) . Antisense oligonucleotides targeting CAG repeats were found to be effective in inhibiting the growth of LNCaP prostate cancer cells (17) . Longer CAG repeats of AR are associated with reduced transcriptional activities, even in the normal range of CAG repeats (18 , 19) . Increasing polyglutamine length negatively affects p160-mediated coactivation of the AR (20) , and elimination of CAG repeats in in vitro systems in both human and rat AR results in a marked elevation of transcriptional activity (18) , which suggests that the presence of this repeat is inhibitory to transactivation. The presence of more than 40 CAG repeats is related to a rare neuromuscular disorder, spinal and bulbar muscular atrophy (Kennedy syndrome), which is also associated with androgen insensitivity, decreased virilization, testicular atrophy, reduced sperm production, and infertility (21) . These data raise the hypothesis that shorter CAG repeats of the AR gene are associated with increased risk of prostate cancer.

There have been several epidemiological studies that have examined the association of CAG repeat lengths with prostate cancer risk. One found that the mean number of CAG repeats was smallest in African Americans, intermediate in Caucasians, and largest in Asians, who, respectively, have a high, intermediate, and low incidence of prostate cancer (22) . Some case-control studies have observed an increase in prostate cancer risk associated with short CAG alleles (22, 23, 24, 25, 26, 27) , although other studies did not find such an association (28, 29, 30, 31, 32, 33) .

The effect of the variation in the length of the GGN tract on AR activity is unclear. The GGN repeats are composed of a consensus sequence of 3 GGT, 1 GGG, 2 GGT, and a variable length of GGC repeats (34) . Results from different studies of transient transfection of reporter constructs have shown that deletion of the GGN tract resulted in either no alteration or increased or decreased AR transcriptional activities (35 , 36) , whereas extension of the GGC repeats from 20 to 48 led to an inhibition (35) . Epidemiological investigations of the association between the number of GGC repeats and prostate cancer risk have produced inconsistent results (22 , 24 , 26 , 31 , 34) .

In the present study, we analyzed the risk of prostate cancer associated with CAG and/or GGC repeats of AR in a case-control study nested within the CARET study.

	Materials and Methods

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Study Population.
The source population for this study was comprised of male participants in the CARET, a double-blind, randomized placebo-controlled trial of ß-carotene (30 mg/day) and retinol palmitate (25,000 IU/day) among two populations of individuals at high risk of lung cancer: asbestos-exposed workers and heavy smokers (37) . Individuals eligible for the asbestos-exposed population were men, ages 45–69, who were current or former smokers with either occupational exposure to asbestos at least 15 years before randomization or a chest X-ray positive for asbestos-related lung disease. Eligible for the heavy-smoker population were men and women 50–69 years of age who were current or recent (quit less than 6 years) cigarette smokers with at least 20 pack-years of cigarette smoking. A total of 18,314 participants were enrolled in the CARET study at six study centers (Fred Hutchinson Cancer Research Center, Seattle, WA, Univ. of California, San Francisco, CA, Univ. of California, Irvine, CA, Univ. of Maryland, Baltimore, MD, Yale University, New Haven, CT, Kaiser Permanente, Portland, OR) from 1985 to 1994 and were followed routinely (as frequently as every 3 months or as infrequently as every year) for end points thereafter. When a CARET participant reported a new cancer diagnosis at a follow-up visit or telephone contact, the diagnosis was confirmed by requesting a pathology report and clinical notes. Those records were reviewed by the members of the end point review committee and the diagnosis confirmed. In many cases, the only records that were available were pathology reports from a needle biopsy. The race of the men was self-identified.

A total of 300 participants with prostate cancer, reported from 1987 to 1998 and confirmed by August 1999, were selected for the present study. Fifty-three others potentially were eligible, but limited availability of blood samples from these men precluded their inclusion in this study. All of the cases were free of lung cancer. A medical oncologist (G. G.) reviewed all of the available clinical records of patients with prostate cancer and determined the grade and stage of the tumor, using the American Joint Committee on Cancer Staging for prostate-cancer 1992 staging system. Complete clinical and pathological staging was missing on 126 cases because the diagnoses were made only by the available pathology and clinical notes. A blinded re-review of a number of cases showed that there was 100% agreement in pathological staging from surgical specimens. For this analysis, "aggressive" cancers were defined as those stage C or D (extraprostatic) or as those stage A or B either with Gleason score 7 or with poorly differentiated tumors. Approximately 46% of the cases had a tumor that met our criteria for being aggressive.

Controls were chosen from male CARET participants who were alive and free of lung and prostate cancer as of August 31, 1999, and were matched to the cases on race, age at enrollment (within 5 years), enrollment study center, and year of randomization. Three cases had no suitable controls with the same year of randomization. For these, we selected a control that had been randomized within a year of the case. Controls also had been followed up in the CARET study through the date of diagnosis of the paired case, at a minimum. All of the participants provided informed consent, and the Institutional Review Offices of all of the participating centers approved the study.

DNA Extraction and Genotype Determination.
Genomic DNA was extracted from whole blood (251 cases and 283 controls) or serum (49 cases and 17 controls) samples that had previously been collected and frozen at -80°C with the use of QIAamp DNA blood Midi kits (Qiagen, Valencia, CA). DNA concentration was determined spectrophotometrically using a Beckman DU-650 spectrophotometer.

To determine the number of CAG repeats in the AR gene, two PCR amplifications (primary and secondary) were performed. The forward and reverse primers used for the primary and secondary PCR were: CAGF1, 5'-GTG CGC GAA GTG ATC CAG AA-3'; CAGR1, 5'-TCT GGG ACG CAA CCT CTC TC-3'; CAGF2, 5'-AGA GGC CGC GAG CGC AGC ACC TC-3'; and CAGR2, 5'-GCT GTG AAG GTT GCT GTT CCT CAT-3'. The primary and secondary reactions contained 0.25 µM respective primers pair, 0.25 mM each dNTP, 1.5 mM MgCl₂, 1x Qiagen buffer, and 0.25 units of Taq polymerase per µl of reaction. Primary cycling parameters included an initial denaturation of 2 min at 95°C, 17 cycles of 94°C for 1 min, 55°C for 1 min, 72°C for 2 min, and a final extension at 72°C for 10 min. The secondary PCR used 1 µl of the primary PCR products as a template and a fraction (0.05 µM) of the Hex-labeled CAGF2 forward primer. Secondary cycling included an initial denaturation of 2 min at 95°C, 35 cycles of 95°C for 1 min, 66°C for 1 min, 72°C for 2 min, and a final extension of 72°C for 10 min.

To determine the number of GGC repeats in the AR gene, two PCR amplifications were performed. The forward and reverse primers for the primary PCR were identical to those described by Sleddens et al. (13) . The PCR primers for the secondary reaction have been previously reported by Irvine et al. (22) . We elected to use the Advantage-GC genomic PCR kit produced by Clontech, which gave better efficiency in amplification than using plaque-forming units of polymerase and high denaturing temperatures to overcome the GC-rich nature of the template. For the primary PCR, 5 ng of genomic DNA isolated from whole blood or 2 µl (equivalent to 1/40 of DNA recovered from 1 ml of serum) of DNA isolated from the serum was used as template for the 10-µl primary PCR. The 10-µl secondary PCR used 1 µl of the primary PCR product as a template and contained 0.2 µM each primer, 0.2 mM dNTP, 1.1 mM magnesium acetate, and reagents from Clontech (Palo Alto, CA) Advantage® GC Genomic PCR kit that included a reaction buffer [with final concentrations at 40 mM tricine-KOH (pH 9.3), 15 mM potassium acetate, 3.5 mM magnesium acetate, 5% DMSO], 1.5 M GC-melt, 0.1–0.12 units/µl Tth polymerase, 0.01 µg/µl Tth Start antibody, 1.0% glycerol, 0.2 mM Tris-HCl (pH 7.5), 4.6 mM KCl, 1.5 µM EDTA, 15 µM DTT, 3.75 µg/ml BSA, and 0.0625 µM forward primer labeled with 6-carboxyfluorescein (6FAM). Cycling conditions included an initial denaturation of 2 min at 95°C, followed by 35 cycles of 94°C for 1 min, 68°C for 3 min, and a final extension at 68°C for 10 min.

After PCR amplification, PCR products for CAG repeats and GGC repeats from each sample were mixed at a ratio of 1:5, then a 2.5-µl aliquot was added to 0.5 µl of Tamra Internal Size-Standard 500 (Applied Biosystems Inc., Foster City, CA) and 12 µl of deionized formamide. The mixture was denatured at 95°C for 5 min and chilled on ice, then run on a Perkin Elmer Applied Biosystems 310 Genetic Analyzer, using Pop-4 polymer. The GeneScan software (Applied Biosystems Inc., Foster City, CA) determined electrophoretic parameters (mobility, peak color, peak height, and peak area). The GeneScan data were analyzed by the Genotyper software to determine the number of CAG or GGC repeats of the unknown samples.

Included in each 96-well plate of samples was a negative control that contained all of the reagents except the genomic DNA and a set of positive controls with a known number of CAG or GGC repeats. If the GeneScan result of the negative control showed a peak in any of the sample bins, sample results from that batch were excluded from analysis, and the samples were retested. The positive controls were created by the purification of the PCR products from a number of homozygous individuals covering a range of CAG or GGC repeats using Pharmacia Sephaglas Band Prep kits (Pharmacia, Piscataway, NJ), cloning the purified products using Novagen pT7Blue Perfectly Blunt Cloning kits (Novagen, Madison, WI) and sequencing the cloned PCR products using Amersham Thermo Sequenase kits (Amersham-Pharmacia, Piscataway, NJ) on a 5% denaturing polyacrylamide gel to determine the exact number of CAG or GGC repeats. These clones were analyzed on a number of runs on the ABI310 Genetic Analyzer; their relative mobility units were used to set Genotyper sample bins. The number of CAG or GGC repeats in the unknown samples was determined by the comparison of their relative mobility units with those of the cloned standards. This system reliably distinguished fragments that differed by a single basepair in length.

Data Analysis.
Univariate t test was used in univariate comparisons of allele frequencies among cases and controls. ORs associated with the different genotypes were estimated by logistic regression. These analyses were adjusted for age and race of the participants.

	Results

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Table 1 presents selected characteristics of prostate cancer cases and controls. The mean age at entry into the trial was 61.2 years (SD, 5.7) for cases and was 60.8 years (SD, 5.9) for controls. The case and control group each had 281 Caucasians (94%), 8 African Americans (3%), and 11 (4%) men with other ethnic origins. The cases and controls were similar in height, weight, body mass index, educational level, and marital status. Among both cases and controls, 50% were former and 50% were current smokers of cigarettes at baseline. There was an equal proportion of cases and controls randomized into the placebo and active arm.

	Discussion

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Three studies observed that men with prostate cancer at relatively young ages at diagnosis tended to have a relatively short CAG repeat length (29 , 33 , 38) . In three other studies, there was a suggestion of an association in relatively younger men (ORs for CAG <22 repeats ranging from 1.38 to 1.72 among men less than 60 years in two studies and less than 66 years in the third), but virtually no association at all in older men (24 , 30 , 31) . We also observed a modest increase in risk (OR, 1.48) among men <60 years with <22 CAG repeats, but the confidence limits were quite wide (0.62–3.56), and in men 60–69 years there was a reduced risk of approximately equal size.

There have been several earlier studies investigating the association of AR-GGC repeat length and prostate cancer risk, and these have produced somewhat conflicting results (Table 7) . Two studies examined the risk of prostate cancer associated with GGC repeat lengths by age of diagnosis (24 , 31) . Stanford et al. (24) observed men with GGC 16 to be at increased risk regardless of age at diagnosis [OR for 16 repeats was 1.40 (95% CI, 0.83–2.39) in men <60 and 2.23 (95% CI, 1.14–4.42) in men 60–64 years]. The other found a reduced risk among men diagnosed at age <66 (OR, 0.36; 95% CI 0.1–1.33) and an increased risk among men diagnosed at age 66 (OR, 1.56; 95% CI, 0.59–4.13 Ref. 31 ). The present study observed a reduced risk associated with 17 repeats in men 70 years and older (OR, 0.51; 95% CI, 0.27–0.94) and no evidence of any association in men younger than this.

When we examined the association of prostate cancer risk in relation to combined CAG and GGC repeats, we found a reduction in prostate cancer risk among men with CAG <22 and GGC 17, or CAG <22 and GGC >17, or CAG 22 and GGC 17 when compared with men with CAG >22, GGC >17 (Table 5) . Our results contrast with those of a study of Caucasians (24) and a study of Chinese (26) , both of which found having a short repeat length for either or both CAG and GGC alleles was associated with increased risk. Similar to our results were those of a sibship study of Caucasians with a family history of prostate cancer. That study found a reduction of risk was associated with a short CAG or GGC allele (Ref. 31 ; Table 7 ). The reasons for the observed differences and similarities among the studies are unclear.

In conclusion, we observed little or no association between the length of CAG and/or GGC repeat sequence in exon 1 of the AR gene and prostate cancer risk in a predominantly Caucasian population. To the extent that we did observe any association, e.g., an increased risk associated with a long sequence for both of these, they were in the direction that was opposite to that observed in some of the prior studies. The aggregate of studies of this question suggests that it is doubtful that, as an independent factor, the commonly observed variation in CAG or GGC repeat length in exon 1 of the AR is associated with the incidence of prostate cancer.

	Acknowledgments

 
We thank the CARET study participants for providing the demographic information and biological specimens, and the principal investigators and staff at the participating CARET study centers for specimen and data collection.

	Footnotes

 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by NIH Grants RO1 CA78812 (to C. C.) and UO1 CA63673 (to G. G.), and by the Interdisciplinary Training Grant 67-2444 (in partial support of N. L.).

² To whom requests for reprints should be addressed, at Fred Hutchinson Cancer Research Center, Mailstop DE-320, 1100 Fairview Avenue North, Seattle, WA 98109-1024. Phone: (206) 667-6644; Fax: (206) 667-2537; E-mail: cchen{at}fhcrc.org

³ The abbreviations used are: AR, androgen receptor; OR, odds ratio; CI, confidence interval; CARET, ß-Carotene and Retinol Efficacy Trial.

Received 12/14/01; revised 4/30/02; accepted 5/ 7/02.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. 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., 8: 338-362, 1987.[Medline]
2. Dearnaley D. P. Cancer of the prostate[Erratum appears in BMJ 308: 975, 1994]. BMJ, 308: 780-784, 1994.[Free Full Text]
3. Noble R. L. The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration. Cancer Res., 37: 1929-1933, 1977.[Abstract/Free Full Text]
4. Pollard M., Luckert P. H., Schmidt M. A. Induction of prostate adenocarcinomas in Lobund Wistar rats by testosterone. Prostate, 3: 563-568, 1982.[Medline]
5. Huggins C., Hodges C. V. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res., 1: 293-297, 1941.[Free Full Text]
6. Huggins C., Stevens R. E., Jr., Hodges C. V. Studies on prostatic cancer. II. The effects of castration on advanced carcinoma of the prostate gland. Arch. Surg., 43: 209-223, 1941.
7. Huggins C., Scott W. W., Hodges C. V. Studies on prostatic cancer. III. The effects of fever, of deoxycorticosterone and of estrogen on clinical patients with metastatic carcinoma of the prostate. J. Urol., 46: 997-1006, 1941.
8. Garnick M. B. Hormonal therapy in the management of prostate cancer: from Huggins to the present. Urology, 49 (3A Suppl.): 5-15, 1997.[Medline]
9. Janne O. A., Palvimo J. J., Kallio P., Mehto M. Androgen receptor and mechanism of androgen action. Ann. Med., 25: 83-89, 1993.[Medline]
10. Jenster G., van der Korput H. A., van Vroonhoven C., van der Kwast T. H., Trapman J., Brinkmann A. O. Domains of the human androgen receptor involved in steroid binding, transcriptional activation, and subcellular localization. Mol. Endocrinol., 5: 1396-1404, 1991.[Abstract]
11. McPhaul M. J. Molecular defects of the androgen receptor. J. Steroid Biochem. Mol. Biol., 69: 315-322, 1999.[Medline]
12. Edwards A., Hammond H. A., Jin L., Caskey C. T., Chakraborty R. Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics, 12: 241-253, 1992.[Medline]
13. Sleddens H. F., Oostra B. A., Brinkmann A. O., Trapman J. Trinucleotide (GGN) repeat polymorphism in the human androgen receptor (AR) gene. Hum. Mol. Genet., 2: 493 1993.[Free Full Text]
14. Riegman P. H., Vlietstra R. J., van der Korput J. A., Brinkmann A. O., Trapman J. The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. Mol. Endocrinol., 5: 1921-1930, 1991.[Abstract]
15. Lu S., Tsai S. Y., Tsai M. J. Regulation of androgen-dependent prostatic cancer cell growth: androgen regulation of CDK2, CDK4, and CKI P16 genes. Cancer Res., 57: 4511-4516, 1997.[Abstract/Free Full Text]
16. Miyashita M. U. T., Ohtsuka Y., Okamura-Oho Y., Shikama Y., Yamada M. Extended polyglutamine selectively interacts with caspase-8 and -10 in nuclear aggregates. Cell Death Differ., 8: 377-386, 2001.[Medline]
17. Eder I. E., Culig Z., Ramoner R., Thurnher M., Putz T., Nessler-Menardi C., Tiefenthaler M., Bartsch G., Klocker H. Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides. Cancer Gene Ther., 7: 997-1007, 2000.[Medline]
18. Chamberlain N. L., Driver E. D., Miesfeld R. L. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res., 22: 3181-3186, 1994.[Abstract/Free Full Text]
19. Kazemi-Esfarjani P., Trifiro M. A., Pinsky L. Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG)_n-expanded neuronopathies. Hum. Mol. Genet., 4: 523-527, 1995.[Abstract/Free Full Text]
20. Irvine R. A., Ma H., Yu M. C., Ross R. K., Stallcup M. R., Coetzee G. A. Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length. Hum. Mol. Genet., 9: 267-274, 2000.[Abstract/Free Full Text]
21. Brooks B. P., Fischbeck K. H. Spinal and bulbar muscular atrophy: a trinucleotide-repeat expansion neurodegenerative disease. Trends Neurosci., 18: 459-461, 1995.[Medline]
22. 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., 55: 1937-1940, 1995.[Abstract/Free Full Text]
23. 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. (Bethesda), 89: 166-170, 1997.[Abstract/Free Full Text]
24. Stanford J. L., Just J. J., Gibbs M., Wicklund K. G., Neal C. L., Blumenstein B. A., Ostrander E. A. Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res., 57: 1194-1198, 1997.[Abstract/Free Full Text]
25. Giovannucci E., Stampfer M. J., Krithivas K., Brown M., 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. USA, 94: 3320-3323, 1997.[Abstract/Free Full Text]
26. Hsing A. W., Gao Y-T., Wu G., Wang X., Deng J., Chen Y-L., Sesterhenn I. A., Mostofi F. K., Benichou J., Chang C. Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. Cancer Res., 60: 5111-5116, 2000.[Abstract/Free Full Text]
27. Xue W., Irvine R. A., Yu M. C., Ross R. K., Coetzee G. A., Ingles S. A. Susceptibility to prostate cancer: interaction between genotypes at the androgen receptor and prostate-specific antigen loci. Cancer Res., 60: 839-841, 2000.[Abstract/Free Full Text]
28. Edwards S. M., Badzioch M. D., Minter R., Hamoudi R., Collins N., Ardern-Jones A., Dowe A., Osborne S., Kelly J., Shearer R., Easton D. F., Saunders G. F., Dearnaley D. P., Eeles R. A. Androgen receptor polymorphisms: association with prostate cancer risk, relapse and overall survival. Int. J. Cancer, 84: 458-465, 1999.[Medline]
29. Bratt O., Borg A., Kristoffersson U., Lundgren R., Zhang Q-X., Olsson H. CAG repeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk. Br. J. Cancer, 81: 672-676, 1999.[Medline]
30. Correa-Cerro L., Wohr G., Haussler J., Berthon P., Drelon E., Mangin P., Fournier G., Cussenot O., Kraus P., Just W., Paiss T., Cantu J. M., Vogel W. (CAG)nCAA and GGN repeats in the human androgen receptor gene are not associated with prostate cancer in a French-German population. Eur. J. Hum. Genet., 7: 357-362, 1999.[Medline]
31. Miller E. A., Stanford J. L., Hsu L., Noonan E., Ostrander E. A. Polymorphic repeats in the androgen receptor gene in high-risk sibships. Prostate, 48: 200-205, 2001.[Medline]
32. Latil A. G., Azzouzi R., Cancel G. S., Guillaume E. C., Cochan-Priollet B., Berthon P. L., Cussenot O. Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways. Cancer (Phila.), 92: 1130-1137, 2001.[Medline]
33. Beilin J., Harewood L., Frydenberg M., Mameghan H., Martyres R. F., Farish S. J., Yue C., Deam D. R., Byron K. A., Zajac J. D. A case-control study of the androgen receptor gene CAG repeat polymorphism in Australian prostate carcinoma subjects. Cancer (Phila.), 92: 941-949, 2001.[Medline]
34. Platz E. A., Giovannucci E., Dahl D. M., Krithivas K., Hennekens C. H., Brown M., Stampfer M. J., Kantoff P. W. The androgen receptor gene GGN microsatellite and prostate cancer risk. Cancer Epidemiol. Biomark. Prev., 7: 379-384, 1998.[Abstract]
35. Jenster G., de Ruiter P. E., van der Korput H. A., Kuiper G. G., Trapman J., Brinkmann A. O. Changes in the abundance of androgen receptor isotypes: effects of ligand treatment, glutamine-stretch variation, and mutation of putative phosphorylation sites. Biochemistry, 33: 14064-14072, 1994.[Medline]
36. Gao T., Marcelli M., McPhaul M. J. Transcriptional activation and transient expression of the human androgen receptor. J. Steroid Biochem. Mol. Biol., 59: 9-20, 1996.[Medline]
37. Omenn G. S. A double-blind randomized trial with ß-carotene and retinol in persons at high risk of lung cancer due to occupational asbestos exposures and/or cigarette smoking. Public Health Rev., 16: 99-125, 1988.[Medline]
38. Hardy D. O., Scher H. I., Bogenreider T., Sabbatini P., Zhang Z. F., Nanus D. M., Catterall J. F. Androgen receptor cag repeat lengths in prostate cancer: correlation with age of onset. J. Clin. Endocrinol. Metab., 81: 4400-4405, 1996.[Abstract]

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