© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 20, 1674-1681,
October 18, 2000
© 2000 Oxford University Press
REPORT |
CYP17 Promoter Polymorphism and Breast Cancer in Australian Women Under Age Forty Years
Affiliations of authors: A. B. Spurdle, X. Chen, G. Chenevix-Trench, Cancer Unit, Joint Experimental Oncology Programme, The Queensland Institute of Medical Research, and The University of Queensland, Brisbane, Australia; J. L. Hopper, G. S. Dite, J. Cui, Centre for Genetic Epidemiology, The University of Melbourne, Carlton, Australia; M. R. E. McCredie, The New South Wales Cancer Council, Kings Cross, Australia, and Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand; G. G. Giles, The Anti-Cancer Council of Victoria, Carlton, Australia; M. C. Southey, D. J. Venter, Peter MacCallum Cancer Institute, Melbourne, Australia, and Department of Pathology, The University of Melbourne, Parkville, Australia; D. F. Easton, Cancer Research Campaign Genetic Epidemiology Unit, Strangeways Research Laboratory, Cambridge, U.K.
Correspondence to: Amanda B. Spurdle, Ph.D., Cancer Unit, The Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Queensland, 4029, Australia (e-mail: mandyS{at}qimr.edu.au).
Background: The cytochrome P450c17
enzyme functions in the steroid biosynthesis pathway, and altered endogenous steroid hormone levels have been reported to be associated with a T to C polymorphism in the 5' promoter region of the CYP17 gene. Because steroid hormone exposure is known to influence breast cancer risk, we conducted a population-based, case–control-family study to assess the relationship between the CYP17 promoter polymorphism and early-onset breast cancer. Methods: Case subjects under 40 years of age at diagnosis of a first primary breast cancer, population-sampled control subjects, and the relatives of both case and control subjects were interviewed to record family history of breast cancer and other risk factors. CYP17 genotype was determined in 369 case subjects, 284 control subjects, and 91 relatives of case subjects. Genotype distributions were compared by logistic regression, and cumulative risk was estimated by a modified segregation analysis. All statistical tests were two-tailed. Results: Compared with the TT genotype (i.e., individuals homozygous for the T allele), the TC genotype was not associated with increased breast cancer risk (P = .7). Compared with the TT and TC genotypes combined, the CC genotype was associated with a relative risk of 1.81 (95% confidence interval [CI] = 1.15–2.86; P = .01) before adjustment for measured risk factors and 1.63 (95% CI = 1.00–2.64; P = .05) after adjustment. There was an excess of CC genotypes in case subjects who had at least one affected first- or second-degree relative, compared with control subjects unstratified by family history of breast cancer (23% versus 11%; P = .006), and these case subjects had a threefold to fourfold higher risk than women of other groups defined by genotype and family history of breast cancer. Analysis of breast cancer in first- and second-degree relatives of case subjects with the CC genotype, excluding two known carriers of a deleterious mutation in BRCA1 or BRCA2, gave a relative hazard in women with the CC genotype of 3.48 (95% CI = 1.13–10.74; P = .04), which is equivalent to a cumulative risk of 16% to age 70 years. Conclusions: The CC genotype may modify the effect of other familial risk factors for early-onset breast cancer.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Chen, M. D. Gammon, S. L. Teitelbaum, J. A. Britton, M. B. Terry, S. Shantakumar, S. M. Eng, Q. Wang, I. Gurvich, A. I. Neugut, et al. Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project Carcinogenesis, April 1, 2008; 29(4): 766 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Henningson, U. Johansson, A. Borg, H. Olsson, and H. Jernstrom CYP17 genotype is associated with short menstrual cycles, early oral contraceptive use and BRCA mutation status in young healthy women Mol. Hum. Reprod., April 1, 2007; 13(4): 231 - 236. [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]
|
|
|
|
 |
|
 N. C. Onland-Moret, C. H. van Gils, M. Roest, D. E. Grobbee, and P. H.M. Peeters Cyp17, Urinary Sex Steroid Levels and Breast Cancer Risk in Postmenopausal Women Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 815 - 820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sharp, A. H. Cardy, S. C. Cotton, and J. Little CYP17 Gene Polymorphisms: Prevalence and Associations with Hormone Levels and Related Factors. A HuGE Review Am. J. Epidemiol., October 15, 2004; 160(8): 729 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamada, F. Sata, E. H. Kato, Y. Saijo, S. Kataoka, M. Morikawa, S. Shimada, T. Yamada, R. Kishi, and H. Minakami A polymorphism in the CYP17 gene and intrauterine fetal growth restriction Mol. Hum. Reprod., January 1, 2004; 10(1): 49 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Sata, H. Yamada, A. Yamada, E. H. Kato, S. Kataoka, Y. Saijo, T. Kondo, J. Tamaki, H. Minakami, and R. Kishi A polymorphism in the CYP17 gene relates to the risk of recurrent pregnancy loss Mol. Hum. Reprod., November 1, 2003; 9(11): 725 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Hopper, G. S. Dite, S. Greenland, K. B. Michels, C. Poole, J. M. Robins, and W. C. Willett RE: "PRESENTING STATISTICAL UNCERTAINTY IN TRENDS AND DOSE-RESPONSE RELATIONS" Am. J. Epidemiol., May 15, 2002; 155(10): 977 - 979. [Full Text] [PDF]
|
|
|
|
|
|
A. B. Spurdle, J. L. Hopper, X. Chen, G. S. Dite, J. Cui, M. R. E. McCredie, G. G. Giles, S. Ellis-Steinborner, D. J. Venter, B. Newman, et al. The BRCA2 372 HH Genotype Is Associated with Risk of Breast Cancer in Australian Women Under Age 60 Years Cancer Epidemiol. Biomarkers Prev., April 1, 2002; 11(4): 413 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Stanford, E. A. Noonan, L. Iwasaki, S. Kolb, R. B. Chadwick, Z. Feng, and E. A. Ostrander A Polymorphism in the CYP17 Gene and Risk of Prostate Cancer Cancer Epidemiol. Biomarkers Prev., March 1, 2002; 11(3): 243 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Ye and J. M. Parry The CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis Mutagenesis, March 1, 2002; 17(2): 119 - 126. [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]
|
|
|
|
|
|
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. J. Lin, J. W. M. Martens, and W. L. Miller NF-1C, Sp1, and Sp3 Are Essential for Transcription of the Human Gene for P450c17 (Steroid 17{alpha}-hydroxylase/17,20 lyase) in Human Adrenal NCI-H295A Cells Mol. Endocrinol., August 1, 2001; 15(8): 1277 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jernstrom, D. Vesprini, H. L. Bradlow, and S. A. Narod Re: CYP17 Promoter Polymorphism and Breast Cancer in Australian Women Under Age Forty Years J Natl Cancer Inst, April 4, 2001; 93(7): 554 - 555. [Full Text] [PDF]
|
|