| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Preventive Medicine [R. K. R., M. C. P., M. C. Y., H. F., B. E. H.], Urology [G. A. C.], and Obstetrics and Gynecology [F. Z. S.], University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033; Institute for Genetic Medicine [J. K. V. R.], University of Southern California School of Medicine, Los Angeles, California 90033; and Epidemiology Program, University of Hawaii at Manoa Cancer Research Center, Honolulu, Hawaii 96813 [L. N. K.]
The prostate is an androgen-regulated organ, which has led to long-standing interest in the role of androgens in prostate carcinogenesis. Although evidence of a hormonal etiology for prostate cancer is strong, it is almost entirely circumstantial. Much of the problem in proving a causal relationship relates to the continued difficulties in reliably measuring human tissue-specific exposure to endogenous steroid hormones.
The international and racial-ethnic variations in prostate cancer incidence, combined with the effects of migration on risk patterns, have suggested that whereas environmental factors are likely to be important, genetic factors might also play a central role in determining prostate cancer risk. We are developing a polygenic model of prostate carcinogenesis focused around a series of genes involved in androgen biosynthesis and androgen activation, transport, and metabolism in the prostate. In this developing model, we have initially targeted four genes based on three main criteria: (a) all encode products that play important roles in inducing androgen stimulation in the prostate; (b) all are polymorphic; and (c) all show substantial allelic variation in the polymorphic marker among the racial-ethnic groups of greatest interest in terms of prostate cancer risk. In addition to studying how the polymorphic markers of interest are related to prostate cancer development within and between racial-ethnic groups, we are concurrently evaluating whether genotypic variations correlate in the anticipated direction with biochemical parameters in vitro and in vivo.
We summarize the development of this model and the state of knowledge related to each of the genes comprising the current model. We discuss the extent to which the current model can explain demographic variation in prostate cancer risk as well as the potential for future expansion of the model to incorporate environmental risk factors as well as additional genes. The model, when fully developed, can potentially provide a basis for targeting populations for screening interventions and/or preventive strategies aimed at the multigene products or at the genes themselves.
1 Supported by National Cancer Institute Grants CA17054, CA54281, CA63464, CA72821, CA68581, and CA53890 and Grant 3 IB-0082 from the State of California.
2 To whom requests for reprints should be addressed, at University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, #803, Los Angeles, CA 90033-0800. Phone: (323) 865-0802; Fax: (323) 865-0103; E-mail: ross_r@froggy.hsc.usc.edu.
Received 5/ 1/98. Accepted 8/18/98.
This article has been cited by other articles:
|
|
 |
|
  J. M. Cunningham, S. J. Hebbring, S. K. McDonnell, M. S. Cicek, G. B. Christensen, L. Wang, S. J. Jacobsen, J. R. Cerhan, M. L. Blute, D. J. Schaid, et al. Evaluation of Genetic Variations in the Androgen and Estrogen Metabolic Pathways as Risk Factors for Sporadic and Familial Prostate Cancer Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 969 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ji, L. Chang, F. Z. Stanczyk, M. Ookhtens, A. Sherrod, and A. Stolz Impaired Dihydrotestosterone Catabolism in Human Prostate Cancer: Critical Role of AKR1C2 as a Pre-Receptor Regulator of Androgen Receptor Signaling Cancer Res., February 1, 2007; 67(3): 1361 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Butcher, N. L. Tetlow, C. Cheung, G. M. Broadhurst, and R. F. Minchin Induction of Human Arylamine N-Acetyltransferase Type I by Androgens in Human Prostate Cancer Cells Cancer Res., January 1, 2007; 67(1): 85 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Kelloff, S. M. Lippman, A. J. Dannenberg, C. C. Sigman, H. L. Pearce, B. J. Reid, E. Szabo, V. C. Jordan, M. R. Spitz, G. B. Mills, et al. Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer--A Plan to Move Forward Clin. Cancer Res., June 15, 2006; 12(12): 3661 - 3697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rajpert-De Meyts Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects Hum. Reprod. Update, May 1, 2006; 12(3): 303 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Douglas, K. A. Zuhlke, J. Beebe-Dimmer, A. M. Levin, S. B. Gruber, D. P. Wood, and K. A. Cooney Identifying Susceptibility Genes for Prostate Cancer--A Family-Based Association Study of Polymorphisms in CYP17, CYP19, CYP11A1, and LH-{beta} Cancer Epidemiol. Biomarkers Prev., August 1, 2005; 14(8): 2035 - 2039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Makridakis and J. K V Reichardt Pharmacogenetic analysis of human steroid 5{alpha} reductase type II: comparison of finasteride and dutasteride J. Mol. Endocrinol., June 1, 2005; 34(3): 617 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Hayes, G. Severi, S. A. Eggleton, E. J.D. Padilla, M. C. Southey, R. L. Sutherland, J. L. Hopper, and G. G. Giles The E211 G>A Androgen Receptor Polymorphism Is Associated with a Decreased Risk of Metastatic Prostate Cancer and Androgenetic Alopecia Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 993 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Parnes, I. M. Thompson, and L. G. Ford Prevention of Hormone-Related Cancers: Prostate Cancer J. Clin. Oncol., January 10, 2005; 23(2): 368 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lukanova and R. Kaaks Endogenous Hormones and Ovarian Cancer: Epidemiology and Current Hypotheses Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 98 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Schmidt, H. Murillo, and D. J. Tindall Gene Expression in Prostate Cancer Cells Treated With the Dual 5 Alpha-Reductase Inhibitor Dutasteride J Androl, November 1, 2004; 25(6): 944 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Schaid The complex genetic epidemiology of prostate cancer Hum. Mol. Genet., April 1, 2004; 13(90001): R103 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Modugno Ovarian Cancer and Polymorphisms in the Androgen and Progesterone Receptor Genes: A HuGE Review Am. J. Epidemiol., February 15, 2004; 159(4): 319 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, J. H. Kim, S. S. Koh, and M. R. Stallcup Synergistic Effects of Coactivators GRIP1 and {beta}-Catenin on Gene Activation: CROSS-TALK BETWEEN ANDROGEN RECEPTOR AND Wnt SIGNALING PATHWAYS J. Biol. Chem., February 6, 2004; 279(6): 4212 - 4220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Xiao, Q. Zhang, F. Jiang, M. Pins, J. M. Kozlowski, and Z. Wang Suppression of Prostate Tumor Growth by U19, a Novel Testosterone-regulated Apoptosis Inducer Cancer Res., August 1, 2003; 63(15): 4698 - 4704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Severi, G. G. Giles, M. C. Southey, A. Tesoriero, W. Tilley, P. Neufing, H. Morris, D. R. English, M. R. E. McCredie, P. Boyle, et al. ELAC2/HPC2 Polymorphisms, Prostate-Specific Antigen Levels, and Prostate Cancer J Natl Cancer Inst, June 4, 2003; 95(11): 818 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Vergnes, J. Phan, A. Stolz, and K. Reue A cluster of eight hydroxysteroid dehydrogenase genes belonging to the aldo-keto reductase supergene family on mouse chromosome 13 J. Lipid Res., March 1, 2003; 44(3): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Lamb, E. Puxeddu, N. Malik, D. L. Stenoien, R. Nigam, G. Y. Saleh, M. Mancini, N. L. Weigel, and M. Marcelli Molecular Analysis of the Androgen Receptor in Ten Prostate Cancer Specimens Obtained Before and After Androgen Ablation J Androl, March 1, 2003; 24(2): 215 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Giovannucci Is the Androgen Receptor CAG Repeat Length Significant for Prostate Cancer? : Commentary re: C. Chen et al., Androgen Receptor Polymorphisms and the Incidence of Prostate Cancer. Cancer Epidemiol. Biomark. Prev., 11: 1033-1040, 2002 Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 985 - 986. [Full Text] [PDF]
|
|
|
|
|
|
S. M. Gapstur, P. H. Gann, P. Kopp, L. Colangelo, C. Longcope, and K. Liu Serum Androgen Concentrations in Young Men: A Longitudinal Analysis of Associations with Age, Obesity, and Race. : The CARDIA Male Hormone Study Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 1041 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rao, R. D. Woodruff, W. N. Wade, T. E. Kute, and S. D. Cramer Genistein and Vitamin D Synergistically Inhibit Human Prostatic Epithelial Cell Growth J. Nutr., October 1, 2002; 132(10): 3191 - 3194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Lippman and W. K. Hong Cancer Prevention Science and Practice Cancer Res., September 15, 2002; 62(18): 5119 - 5125. [Full Text] [PDF]
|
|
|
|
|
|
G. Coetzee and R. Irvine Size of the Androgen Receptor CAG Repeat and Prostate Cancer: Does It Matter? J. Clin. Oncol., September 1, 2002; 20(17): 3572 - 3573. [Full Text] [PDF]
|
|
|
|
|
|
K. A. Nelson and J. S. Witte Androgen Receptor CAG Repeats and Prostate Cancer Am. J. Epidemiol., May 15, 2002; 155(10): 883 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Munkarah, R. Morris, P. Baumann, G. Deppe, J. Malone, M. P. Diamond, and G. M. Saed Effects of Prostaglandin E2 on Proliferation and Apoptosis of Epithelial Ovarian Cancer Cells Reproductive Sciences, May 1, 2002; 9(3): 168 - 173. [Abstract] [PDF]
|
|
|
|
|
|
A. W. Hsing, A. P. Chokkalingam, Y.-T. Gao, G. Wu, X. Wang, J. Deng, J. Cheng, I. A. Sesterhenn, F. K. Mostofi, T. Chiang, et al. Polymorphic CAG/CAA Repeat Length in the AIB1/SRC-3 Gene and Prostate Cancer Risk: A Population-based Case-Control Study Cancer Epidemiol. Biomarkers Prev., April 1, 2002; 11(4): 337 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Pearce, N. M. Makridakis, R. K. Ross, M. C. Pike, L. N. Kolonel, B. E. Henderson, and J. K. V. Reichardt Steroid 5-{alpha} Reductase Type II V89L Substitution Is Not Associated with Risk of Prostate Cancer in a Multiethnic Population Study Cancer Epidemiol. Biomarkers Prev., April 1, 2002; 11(4): 417 - 418. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Haiman, M. Brown, S. E. Hankinson, D. Spiegelman, G. A. Colditz, W. C. Willett, P. W. Kantoff, and D. J. Hunter The Androgen Receptor CAG Repeat Polymorphism and Risk of Breast Cancer in the Nurses' Health Study Cancer Res., February 1, 2002; 62(4): 1045 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-W. Yu, Y.-C. Yang, S.-Y. Yang, S.-W. Cheng, Y.-F. Liaw, S.-M. Lin, and C.-J. Chen Hormonal Markers and Hepatitis B Virus-Related Hepatocellular Carcinoma Risk: a Nested Case-Control Study Among Men J Natl Cancer Inst, November 7, 2001; 93(21): 1644 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Hsing, C. Chen, A. P. Chokkalingam, Y.-T. Gao, D. A. Dightman, H. T. Nguyen, J. Deng, J. Cheng, I. A. Sesterhenn, F. K. Mostofi, et al. Polymorphic Markers in the SRD5A2 Gene and Prostate Cancer Risk: A Population-based Case-control Study Cancer Epidemiol. Biomarkers Prev., October 1, 2001; 10(10): 1077 - 1082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kittles, R. K. Panguluri, W. Chen, A. Massac, C. Ahaghotu, A. Jackson, F. Ukoli, L. Adams-Campbell, W. Isaacs, and G. M. Dunston CYP17 Promoter Variant Associated with Prostate Cancer Aggressiveness in African Americans Cancer Epidemiol. Biomarkers Prev., September 1, 2001; 10(9): 943 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Haiman, M. J. Stampfer, E. Giovannucci, J. Ma, N. E. Decalo, P. W. Kantoff, and D. J. Hunter The Relationship between a Polymorphism in CYP17 with Plasma Hormone Levels and Prostate Cancer Cancer Epidemiol. Biomarkers Prev., July 1, 2001; 10(7): 743 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Wu, A. S. Whittemore, L. N. Kolonel, F. Z. Stanczyk, E. M. John, R. P. Gallagher, and D. W. West Lifestyle Determinants of 5{{alpha}}-Reductase Metabolites in Older African-American, White, and Asian-American Men Cancer Epidemiol. Biomarkers Prev., May 1, 2001; 10(5): 533 - 538. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. G. Söderström, C. Bjelfman, E. Brekkan, B. Ask, L. Egevad, B. J. Norlén, and A. Rane Messenger Ribonucleic Acid Levels of Steroid 5{{alpha}}-Reductase 2 in Human Prostate Predict the Enzyme Activity J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 855 - 858. [Abstract] [Full Text]
|
|
|
|
|
|
B. Lin, J. T. White, C. Ferguson, S. Wang, R. Vessella, R. Bumgarner, L. D. True, L. Hood, and P. S. Nelson Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium Cancer Res., February 1, 2001; 61(4): 1611 - 1618. [Abstract] [Full Text]
|
|
|
|
|
|
M.-W. Yu, S.-W. Cheng, M.-W. Lin, S.-Y. Yang, Y.-F. Liaw, H.-C. Chang, T.-J. Hsiao, S.-M. Lin, S.-D. Lee, P.-J. Chen, et al. Androgen-Receptor Gene CAG Repeats, Plasma Testosterone Levels, and Risk of Hepatitis B-Related Hepatocellular Carcinoma J Natl Cancer Inst, December 20, 2000; 92(24): 2023 - 2028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Bosland Chapter 2: The Role of Steroid Hormones in Prostate Carcinogenesis J Natl Cancer Inst Monographs, July 1, 2000; 2000(27): 39 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Henderson and H. S. Feigelson Hormonal carcinogenesis Carcinogenesis, March 1, 2000; 21(3): 427 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Jaffe, S. B. Malkowicz, A. H. Walker, S. MacBride, R. Peschel, J. Tomaszewski, K. Van Arsdalen, A. J. Wein, and T. R. Rebbeck Association of SRD5A2 Genotype and Pathological Characteristics of Prostate Tumors Cancer Res., March 1, 2000; 60(6): 1626 - 1630. [Abstract] [Full Text]
|
|
|
|
|
|
W. Xue, R. A. Irvine, M. C. Yu, R. K. Ross, G. A. Coetzee, and S. A. Ingles Susceptibility to Prostate Cancer: Interaction between Genotypes at the Androgen Receptor and Prostate-specific Antigen Loci Cancer Res., February 1, 2000; 60(4): 839 - 841. [Abstract] [Full Text]
|
|
|
|
|
|
R. A. Irvine, H. Ma, M. C. Yu, R. K. Ross, M. R. Stallcup, and G. A. Coetzee Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length Hum. Mol. Genet., January 22, 2000; 9(2): 267 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Febbo, P. W. Kantoff, E. A. Platz, D. Casey, S. Batter, E. Giovannucci, C. H. Hennekens, and M. J. Stampfer The V89L Polymorphism in the 5{{alpha}}-Reductase Type 2 Gene and Risk of Prostate Cancer Cancer Res., December 1, 1999; 59(23): 5878 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Marcelli and G. R. Cunningham Hormonal Signaling in Prostatic Hyperplasia and Neoplasia J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3463 - 3468. [Full Text] [PDF]
|
|
|
|
|
|
R. T. Prehn On the Prevention and Therapy of Prostate Cancer by Androgen Administration Cancer Res., September 1, 1999; 59(17): 4161 - 4164. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
