This Article Full Text 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 Spurdle, A. B. Articles by Chenevix-Trench, G. Search for Related Content PubMed PubMed Citation Articles by Spurdle, A. B. Articles by Chenevix-Trench, G.

The Progesterone Receptor Exon 4 Val660Leu G/T Polymorphism and Risk of Breast Cancer in Australian Women¹

Oncology Division, Joint Experimental Oncology Programme, The Queensland Institute of Medical Research, and The University of Queensland, Brisbane, Queensland, 4029, Australia [A. B. S., X. C., G. C-T.]; Centre for Genetic Epidemiology, The University of Melbourne, Carlton, Victoria 3053 Australia [J. L. H.]; The New South Wales Cancer Council, Kings Cross, NSW 2011 Australia, and Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand [M. R. E. M.]; The Anti-Cancer Council of Victoria, Carlton, Victoria 3053 Australia [G. G. G.]; and Peter MacCallum Cancer Institute, Melbourne, Australia, and Department of Pathology, The University of Melbourne, Parkville, Victoria 3053 Australia [D. J. V., M. C. S.]

An Alu insertion polymorphism of the progesterone receptor (PR) wasreported recently to be associated with a reduced risk of breast cancer, with risks of 0.8- and 0.3-fold associated with the heterozygote and homozygote genotypes, respectively. This intronic variant is considered to be in linkage disequilibrium with an exon 4 hinge region G to T Val660Leu polymorphism. We investigated whether the exon 4 PR polymorphism was associated with breast cancer in Australian women, using a population-based study of 1452 cases and 793 controls, half of whom were <40 years of age, and the other half were 40–59 years of age. There was no difference in genotype distribution between cases and controls (P = 0.5) and no evidence of risk associated with either the GT or TT genotypes compared with the common GG genotype. The adjusted odds ratios (ORs) were 0.97 (95% confidence interval, 0.79–1.19) and 1.52 (95% confidence interval, 0.87–2.66), respectively (P = 0.8 and 0.1), and the results were independent of age and family history of breast cancer. Our data provided no support for the previously reported decreased risk of breast cancer associated with the T allele, with 80% power to detect an OR of 0.8 or less for the heterozygote genotype and 90% power to detect an OR of 0.3 or less for the rare homozygous TT genotype. There was also no support for a greatly increased risk of breast cancer associated with the T allele, given that we had 80% power to detect risks of 1.3 and 2.0 associated with the GT and TT genotypes, respectively. We therefore conclude that this polymorphism is not associated with a markedly reduced or increased risk of breast cancer in Australian women <60 years of age. However, despite its considerable size, our study cannot exclude a small reduced or increased risk associated with the T allele, especially the rare TT genotype.

This article has been cited by other articles:

				Guoyang Luo, T. Morgan, M. O. Bahtiyar, V. V. Snegovskikh, F. Schatz, E. Kuczynski, E. F. Funai, A. T. Dulay, S.-T. J. Huang, C. S. Buhimschi, et al. Single Nucleotide Polymorphisms in the Human Progesterone Receptor Gene and Spontaneous Preterm Birth Reproductive Sciences, February 1, 2008; 15(2): 147 - 155. [Abstract] [PDF]

				T. R. Rebbeck, A. B. Troxel, S. Norman, G. Bunin, A. DeMichele, R. Schinnar, J. A. Berlin, and B. L. Strom Pharmacogenetic Modulation of Combined Hormone Replacement Therapy by Progesterone-Metabolism Genotypes in Postmenopausal Breast Cancer Risk Am. J. Epidemiol., December 15, 2007; 166(12): 1392 - 1399. [Abstract] [Full Text] [PDF]

				The Breast Cancer Association Consortium Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst, October 4, 2006; 98(19): 1382 - 1396. [Abstract] [Full Text] [PDF]

				K. A. Pooley, C. S. Healey, P. L. Smith, P. D.P. Pharoah, D. Thompson, L. Tee, J. West, C. Jordan, D. F. Easton, B. A.J. Ponder, et al. Association of the progesterone receptor gene with breast cancer risk: a single-nucleotide polymorphism tagging approach. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 675 - 682. [Abstract] [Full Text] [PDF]

				F. J.B. van Duijnhoven, P. H.M. Peeters, R. M.L. Warren, S. A. Bingham, A. G. Uitterlinden, P. A.H. van Noord, E. M. Monninkhof, D. E. Grobbee, and C. H. van Gils Influence of Estrogen Receptor {alpha} and Progesterone Receptor Polymorphisms on the Effects of Hormone Therapy on Mammographic Density. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 462 - 467. [Abstract] [Full Text] [PDF]

				S. A. Treloar, Z. Z. Zhao, T. Armitage, D. L. Duffy, J. Wicks, D. T. O'Connor, N. G. Martin, and G. W. Montgomery Association between polymorphisms in the progesterone receptor gene and endometriosis Mol. Hum. Reprod., September 1, 2005; 11(9): 641 - 647. [Abstract] [Full Text] [PDF]

				P. M. Webb, J. L. Hopper, B. Newman, X. Chen, L. Kelemen, G. G. Giles, M. C. Southey, G. Chenevix-Trench, and A. B. Spurdle Double-Strand Break Repair Gene Polymorphisms and Risk of Breast or Ovarian Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 319 - 323. [Abstract] [Full Text] [PDF]

				C. L. Pearce, J. N. Hirschhorn, A. H. Wu, N. P. Burtt, D. O. Stram, S. Young, L. N. Kolonel, B. E. Henderson, D. Altshuler, and M. C. Pike Clarifying the PROGINS Allele Association in Ovarian and Breast Cancer Risk: A Haplotype-Based Analysis J Natl Cancer Inst, January 5, 2005; 97(1): 51 - 59. [Abstract] [Full Text] [PDF]

				Y. Zhu, M. R. Spitz, C. I. Amos, J. Lin, M. B. Schabath, and X. Wu An Evolutionary Perspective on Single-Nucleotide Polymorphism Screening in Molecular Cancer Epidemiology Cancer Res., March 15, 2004; 64(6): 2251 - 2257. [Abstract] [Full Text] [PDF]

				I. De Vivo, S. E. Hankinson, G. A. Colditz, and D. J. Hunter A Functional Polymorphism in the Progesterone Receptor Gene Is Associated with an Increase in Breast Cancer Risk Cancer Res., September 1, 2003; 63(17): 5236 - 5238. [Abstract] [Full Text] [PDF]