Mutagenesis, Vol. 17, No. 2, 119-126,
March 2002
© 2002 UK Environmental Mutagen Society/Oxford University Press
The CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis
Bioinformatics Group, Centre for Molecular Genetics and Toxicology, School of Biological Sciences, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK
Inter-individual differences in susceptibility to breast cancer are partially mediated through the levels of endogenous and exogenous steroid hormones. The CYP17 gene encodes P450c17
, an enzyme that is involved in the metabolism of steroid hormones. Increased endogenous steroid hormone levels have been associated with a MspA1 polymorphism in the 5'-promoter region of the CYP17 gene. The CYP17 MspA1 polymorphism has been postulated as being associated with the risk of developing breast cancer. However, the association between the CYP17 MspA1 polymorphism and breast cancer risk has been controversial in the literature. To re-examine this controversy, we have undertaken a meta-analysis of 15 case–control studies, which included a total of 4227 breast cancer cases and 4730 individual controls. The odds ratio (OR) was used to evaluate the risk of breast cancer for each study, using homozygosity of the wild-type allele as the control group. Statistical analysis showed no evidence of heterogeneity within the studies. The pooled ORs of breast cancer associated with the combined variant (A1/A2 + A2/A2) and the homozygous genotype (A2/A2) were 0.98 (95% CI 0.89–1.07) and 1.05 (95% CI 0.87–1.21), respectively. Similarly, the pooled ORs of advanced breast cancer associated with the combined variant and the homozygous genotype were 0.96 (95% CI 0.77–1.20) and 0.88 (95% CI 0.55–1.41), respectively. A pooling of the studies was also conducted for the various ethnic groups, but failed to show an association of CYP17 MspA1 polymorphism with breast cancer risk in the different ethnic groups. In addition, our results show that a possible protective effect for breast cancer risk of a later age at menarche was mainly limited to women with the A1 homozygous genotype. The OR for age at menarche (
13) was 0.87 (95% CI 0.62–1.17). Our results suggest that CYP17 MspA1 polymorphism may be at best a weak modifier of breast cancer risk but is not a significant independent risk factor.
1 To whom correspondence should be addressed. Tel: +44 1792 205678; Fax: +44 1792 295447; Email: bazheye{at}swansea.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. C. Sakoda, C. Blackston, J. A. Doherty, R. M. Ray, M. G. Lin, H. Stalsberg, D. L. Gao, Z. Feng, D. B. Thomas, and C. Chen Polymorphisms in Steroid Hormone Biosynthesis Genes and Risk of Breast Cancer and Fibrocystic Breast Conditions in Chinese Women Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1066 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
V. W. Setiawan, F. R. Schumacher, C. A. Haiman, D. O. Stram, D. Albanes, D. Altshuler, G. Berglund, J. Buring, E. E. Calle, F. Clavel-Chapelon, et al. CYP17 Genetic Variation and Risk of Breast and Prostate Cancer from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2237 - 2246. [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]
|
|
|
|
 |
|
 J. P. A. Ioannidis Common genetic variants for breast cancer: 32 largely refuted candidates and larger prospects. J Natl Cancer Inst, October 4, 2006; 98(19): 1350 - 1353. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Piller, E. Verla-Tebit, S. Wang-Gohrke, J. Linseisen, and J. Chang-Claude CYP17 Genotype Modifies the Association between Lignan Supply and Premenopausal Breast Cancer Risk in Humans J. Nutr., June 1, 2006; 136(6): 1596 - 1603. [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]
|
|
|
|
 |
|
 J. Somner, S. McLellan, J. Cheung, Y. T. Mak, M. L. Frost, K. M. Knapp, A. S. Wierzbicki, M. Wheeler, I. Fogelman, S. H. Ralston, et al. Polymorphisms in the P450 c17 (17-Hydroxylase/17,20-Lyase) and P450 c19 (Aromatase) Genes: Association with Serum Sex Steroid Concentrations and Bone Mineral Density in Postmenopausal Women J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 344 - 351. [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]
|
|
|
|
|
|
C. Ntais, A. Polycarpou, and J. P. A. Ioannidis Association of the CYP17 Gene Polymorphism with the Risk of Prostate Cancer: A Meta-Analysis Cancer Epidemiol. Biomarkers Prev., February 1, 2003; 12(2): 120 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Feigelson, R. McKean-Cowdin, and B. E. Henderson Concerning the CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis Mutagenesis, September 1, 2002; 17(5): 445 - 446. [Full Text] [PDF]
|
|
|
|
|
|
Z. Ye and J. M. Parry Concerning the CYP17 MSPA1 polymorphism and breast cancer risk: a meta-analysis Mutagenesis, September 1, 2002; 17(5): 447 - 448. [Full Text] [PDF]
|
|