This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taylor, J. A. Articles by Bell, D. A. Search for Related Content PubMed PubMed Citation Articles by Taylor, J. A. Articles by Bell, D. A.

Association of Prostate Cancer with Vitamin D Receptor Gene Polymorphism

Epidemiology Branch [J. A. T.], Laboratory of Biochemical Risk Analysis [A. H., M. W., D. A. B.], National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, and University of North Carolina, Chapel Hill, North Carolina 27599 [G. P., J. L. M.]

The incidence of prostate cancer in the United States is second only to skin cancers, and the disease kills almost the same number of men as breast cancer does women. Relatively few risk factors are known for prostate cancer, although several lines of evidence suggest that vitamin D may be an important determinant of prostate cancer risk. A series of common polymorphisms in the vitamin D receptor gene were recently reported to be associated with bone density and risk of osteoporosis (Morrison et al., Nature (Lond.), 367: 284–287, 1994). These genetic variants have been correlated with both circulating levels of active vitamin D hormone and in vitro measures of gene expression (Morrison et al., Nature (Lond.), 367: 284–287, 1994). We tested the hypothesis that vitamin D receptor gene polymorphisms are associated with prostate cancer risk using a case-control study of 108 men undergoing radical prostatectomy and 170 male urology clinic controls with no history of cancer. Among the white control group, 22% were homozygous for the presence of a TaqI RFLP at codon 352 (genotype tt), but only 8% of cases had this genotype (P < 0.01). A similar trend was seen among the small number of blacks in this study (13% for controls, 8% for cases), although the difference was not statistically significant. Race-adjusted combined analysis suggests that men who are homozygous for the t allele (shown to correlate with higher serum levels of the active form of vitamin D) have one-third the risk of developing prostate cancer requiring prostatectomy compared to men who are heterozygotes or homozygous for the T allele (odds ratio_MH = 0.34; 95% confidence interval, 0.16–0.76; P < 0.01). These results support recent ecological, population, and in vitro studies suggesting that vitamin D is an important determinant of prostate cancer risk and, if confirmed, suggest strategies for chemoprevention of this common cancer.

¹ To whom requests for reprints should be addressed, at Mail Drop A3-05, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709.

² Present address: Laboratory of Cellular and Molecular Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland. A. H. was supported in part by the Finnish Academy of Sciences, the Finnish Cancer Society, and the Finnish Work Environmental Fund.

Received 6/26/96. Accepted 7/31/96.

This article has been cited by other articles:

				G. Lurie, L. R. Wilkens, P. J. Thompson, K. E. McDuffie, M. E. Carney, K. Y. Terada, and M. T. Goodman Vitamin D Receptor Gene Polymorphisms and Epithelial Ovarian Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2566 - 2571. [Abstract] [Full Text] [PDF]

				G. E. Mullin and A. Dobs Vitamin D and Its Role in Cancer and Immunity: A Prescription for Sunlight Nutr Clin Pract, June 1, 2007; 22(3): 305 - 322. [Abstract] [Full Text] [PDF]

				P. Tuohimaa, L. Tenkanen, H. Syvala, S. Lumme, T. Hakulinen, J. Dillner, and M. Hakama Interaction of Factors Related to the Metabolic Syndrome and Vitamin D on Risk of Prostate Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2007; 16(2): 302 - 307. [Abstract] [Full Text] [PDF]

				I. B. Jeffery, S. F. Madden, P. A. McGettigan, G. Perriere, A. C. Culhane, and D. G. Higgins Integrating transcription factor binding site information with gene expression datasets Bioinformatics, February 1, 2007; 23(3): 298 - 305. [Abstract] [Full Text] [PDF]

				M. S. Cicek, X. Liu, F. R. Schumacher, G. Casey, and J. S. Witte Vitamin D Receptor Genotypes/Haplotypes and Prostate Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2549 - 2552. [Abstract] [Full Text] [PDF]

				E. M. John, G. G. Schwartz, J. Koo, D. Van Den Berg, and S. A. Ingles Sun Exposure, Vitamin D Receptor Gene Polymorphisms, and Risk of Advanced Prostate Cancer Cancer Res., June 15, 2005; 65(12): 5470 - 5479. [Abstract] [Full Text] [PDF]

				V. M. Hayes, G. Severi, E. J.D. Padilla, S. A. Eggleton, M. C. Southey, R. L. Sutherland, J. L. Hopper, and G. G. Giles Genetic Variants in the Vitamin D Receptor Gene and Prostate Cancer Risk Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 997 - 999. [Abstract] [Full Text] [PDF]

				J. E. Garber and K. Offit Hereditary Cancer Predisposition Syndromes J. Clin. Oncol., January 10, 2005; 23(2): 276 - 292. [Abstract] [Full Text] [PDF]

				A. H. Poon, C. Laprise, M. Lemire, A. Montpetit, D. Sinnett, E. Schurr, and T. J. Hudson Association of Vitamin D Receptor Genetic Variants with Susceptibility to Asthma and Atopy Am. J. Respir. Crit. Care Med., November 1, 2004; 170(9): 967 - 973. [Abstract] [Full Text] [PDF]

				I. Oakley-Girvan, D. Feldman, T. R. Eccleshall, R. P. Gallagher, A. H. Wu, L. N. Kolonel, J. Halpern, R. R. Balise, D. W. West, R. S. Paffenbarger Jr., et al. Risk of Early-Onset Prostate Cancer in Relation to Germ Line Polymorphisms of the Vitamin D Receptor Cancer Epidemiol. Biomarkers Prev., August 1, 2004; 13(8): 1325 - 1330. [Abstract] [Full Text] [PDF]

				C. Ntais, A. Polycarpou, and J. P. A. Ioannidis Vitamin D Receptor Gene Polymorphisms and Risk of Prostate Cancer: A Meta-analysis Cancer Epidemiol. Biomarkers Prev., December 1, 2003; 12(12): 1395 - 1402. [Abstract] [Full Text] [PDF]

				N. Ikeda, H. Uemura, H. Ishiguro, M. Hori, M. Hosaka, S. Kyo, K.-i. Miyamoto, E. Takeda, and Y. Kubota Combination Treatment with 1{alpha},25-Dihydroxyvitamin D3 and 9-cis-Retinoic Acid Directly Inhibits Human Telomerase Reverse Transcriptase Transcription in Prostate Cancer Cells Mol. Cancer Ther., August 1, 2003; 2(8): 739 - 746. [Abstract] [Full Text] [PDF]

				S. M. Boyapati, R. M. Bostick, K. A. McGlynn, M. F. Fina, W. M. Roufail, K. R. Geisinger, M. Wargovich, A. Coker, and J. R. Hebert Calcium, Vitamin D, and Risk for Colorectal Adenoma: Dependency on Vitamin D Receptor BsmI Polymorphism and Nonsteroidal Anti-Inflammatory Drug Use? Cancer Epidemiol. Biomarkers Prev., July 1, 2003; 12(7): 631 - 637. [Abstract] [Full Text] [PDF]

				Y. Xu, A. Shibata, J. E. McNeal, T. A. Stamey, D. Feldman, and D. M. Peehl Vitamin D Receptor Start Codon Polymorphism (FokI) and Prostate Cancer Progression Cancer Epidemiol. Biomarkers Prev., January 1, 2003; 12(1): 23 - 27. [Abstract] [Full Text] [PDF]

				E. P. Gelmann, D. J. Steadman, J. Ma, N. Ahronovitz, H. J. Voeller, S. Swope, M. Abbaszadegan, K. M. Brown, K. Strand, R. B. Hayes, et al. Occurrence of NKX3.1 C154T Polymorphism in Men with and without Prostate Cancer and Studies of Its Effect on Protein Function Cancer Res., May 1, 2002; 62(9): 2654 - 2659. [Abstract] [Full Text] [PDF]

				U. Peters, K. A. McGlynn, N. Chatterjee, E. Gunter, M. Garcia-Closas, N. Rothman, and R. Sinha Vitamin D, Calcium, and Vitamin D Receptor Polymorphism in Colorectal Adenomas Cancer Epidemiol. Biomarkers Prev., December 1, 2001; 10(12): 1267 - 1274. [Abstract] [Full Text] [PDF]

				J. M Chan, M. J Stampfer, J. Ma, P. H Gann, J M. Gaziano, and E. L Giovannucci Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study Am. J. Clinical Nutrition, October 1, 2001; 74(4): 549 - 554. [Abstract] [Full Text] [PDF]

				K. A. Moffatt, W. U. Johannes, T. E. Hedlund, and G. J. Miller Growth Inhibitory Effects of 1{alpha}, 25-Dihydroxyvitamin D3 Are Mediated by Increased Levels of p21 in the Prostatic Carcinoma Cell Line ALVA-31 Cancer Res., October 1, 2001; 61(19): 7122 - 7129. [Abstract] [Full Text] [PDF]

				C. J. Luscombe, M. E. French, S. Liu, M. F. Saxby, P. W. Jones, A. A. Fryer, and R. C. Strange Outcome in prostate cancer associations with skin type and polymorphism in pigmentation-related genes Carcinogenesis, September 1, 2001; 22(9): 1343 - 1347. [Abstract] [Full Text] [PDF]

				I. Guleva, U. Seitzer, and T. Niimi VITAMIN D RECEPTOR GENE POLYMORPHISM IN PATIENTS WITH SARCOIDOSIS Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 760 - 761. [Full Text] [PDF]

				C. Crescioli, M. Maggi, G. B. Vannelli, M. Luconi, R. Salerno, T. Barni, M. Gulisano, G. Forti, and M. Serio Effect of a Vitamin D3 Analogue on Keratinocyte Growth Factor-Induced Cell Proliferation in Benign Prostate Hyperplasia J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2576 - 2583. [Abstract] [Full Text]

				P. E. Hutchinson, J. E. Osborne, J. T. Lear, A. G. Smith, P. W. Bowers, P. N. Morris, P. W. Jones, C. York, R. C. Strange, and A. A. Fryer Vitamin D Receptor Polymorphisms Are Associated with Altered Prognosis in Patients with Malignant Melanoma Clin. Cancer Res., February 1, 2000; 6(2): 498 - 504. [Abstract] [Full Text]

				T. Habuchi, T. Suzuki, R. Sasaki, L. Wang, K. Sato, S. Satoh, T. Akao, N. Tsuchiya, N. Shimoda, Y. Wada, et al. Association of Vitamin D Receptor Gene Polymorphism with Prostate Cancer and Benign Prostatic Hyperplasia in a Japanese Population Cancer Res., January 1, 2000; 60(2): 305 - 308. [Abstract] [Full Text]

				G. P. Jarvik, J. L. Stanford, E. L. Goode, R. McIndoe, S. Kolb, M. Gibbs, L. Hood, and E. A. Ostrander Confirmation of Prostate Cancer Susceptibility Genes Using High-Risk Families J Natl Cancer Inst Monographs, December 1, 1999; 1999(26): 81 - 87. [Abstract] [Full Text]

				A. M. Dunning, S. McBride, J. Gregory, F. Durocher, N. A. Foster, C. S. Healey, N. Smith, P. D. P. Pharoah, R. N. Luben, D. F. Easton, et al. No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer Carcinogenesis, November 1, 1999; 20(11): 2131 - 2135. [Abstract] [Full Text] [PDF]

				T. NIIMI, H. TOMITA, S. SATO, H. KAWAGUCHI, K. AKITA, H. MAEDA, Y. SUGIURA, and R. UEDA Vitamin D Receptor Gene Polymorphism in Patients with Sarcoidosis Am. J. Respir. Crit. Care Med., October 1, 1999; 160(4): 1107 - 1109. [Abstract] [Full Text]

				R. M. Lunn, D. A. Bell, J. L. Mohler, and J. A. Taylor Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2) Carcinogenesis, September 1, 1999; 20(9): 1727 - 1731. [Abstract] [Full Text] [PDF]

				M. P. Matikainen, J. Schleutker, P. Morsky, O.-P. Kallioniemi, and T. L. J. Tammela Detection of Subclinical Cancers by Prostate-specific Antigen Screening in Asymptomatic Men from High-Risk Prostate Cancer Families Clin. Cancer Res., June 1, 1999; 5(6): 1275 - 1279. [Abstract] [Full Text] [PDF]

				A.-C. Lundin, P. Soderkvist, B. Eriksson, M. Bergman-Jungestrom, and S. Wingren Association of Breast Cancer Progression with a Vitamin D Receptor Gene Polymorphism Cancer Res., May 1, 1999; 59(10): 2332 - 2334. [Abstract] [Full Text] [PDF]

				P. J. Malloy, J. W. Pike, and D. Feldman The Vitamin D Receptor and the Syndrome of Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets Endocr. Rev., April 1, 1999; 20(2): 156 - 188. [Abstract] [Full Text]

				B. L. Lokeshwar, G. G. Schwartz, M. G. Selzer, K. L. Burnstein, S.-H. Zhuang, N. L. Block, and L. Binderup Inhibition of Prostate Cancer Metastasis in Vivo: A Comparison of 1,25-Dihydroxyvitamin D (Calcitriol) and EB1089 Cancer Epidemiol. Biomarkers Prev., March 1, 1999; 8(3): 241 - 248. [Abstract] [Full Text] [PDF]

				E. Ruijter, C. van de Kaa, G. Miller, D. Ruiter, F. Debruyne, and J. Schalken Molecular Genetics and Epidemiology of Prostate Carcinoma Endocr. Rev., February 1, 1999; 20(1): 22 - 45. [Abstract] [Full Text]

				R. Sinha and N. Caporaso Diet, Genetic Susceptibility and Human Cancer Etiology J. Nutr., February 1, 1999; 129(2): 556 - 556. [Abstract] [Full Text] [PDF]

				F. J. Van schooten, A. Hirvonen, L. M. Maas, B. A. De mol, J. C. S. kleinjans, D. A. Bell, and J. D. Durrer Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking, and aromatic DNA adduct levels in human right atrial tissue FASEB J, October 1, 1998; 12(13): 1409 - 1417. [Abstract] [Full Text]

				C. Lopez-Otin and E. P. Diamandis Breast and Prostate Cancer: An Analysis of Common Epidemiological, Genetic, and Biochemical Features Endocr. Rev., August 1, 1998; 19(4): 365 - 396. [Abstract] [Full Text] [PDF]

				P. J. Russell, S. Bennett, and P. Stricker Growth factor involvement in progression of prostate cancer Clin. Chem., April 1, 1998; 44(4): 705 - 723. [Abstract] [Full Text] [PDF]

				K.-i. Miyamoto, R. A. Kesterson, H. Yamamoto, Y. Taketani, E. Nishiwaki, S. Tatsumi, Y. Inoue, K. Morita, E. Takeda, and J. W. Pike Structural Organization of the Human Vitamin D Receptor Chromosomal Gene and Its Promoter Mol. Endocrinol., July 1, 1997; 11(8): 1165 - 1179. [Abstract] [Full Text]