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Age-specific association of steroid hormone pathway gene polymorphisms with breast cancer risk†
Article first published online: 13 APR 2007
Copyright © 2007 American Cancer Society
Volume 109, Issue 10, pages 1940–1948, 15 May 2007
How to Cite
Ralph, D. A., Zhao, L. P., Aston, C. E., Manjeshwar, S., Pugh, T. W., DeFreese, D. C., Gramling, B. A., Shimasaki, C. D. and Jupe, E. R. (2007), Age-specific association of steroid hormone pathway gene polymorphisms with breast cancer risk. Cancer, 109: 1940–1948. doi: 10.1002/cncr.22634
All authors are either employees or consultants of InterGenetics Incorporated
- Issue published online: 25 APR 2007
- Article first published online: 13 APR 2007
- Manuscript Accepted: 12 FEB 2007
- Manuscript Revised: 28 JAN 2007
- Manuscript Received: 27 OCT 2006
- U.S. Army Breast Cancer Research Program. Grant Number: DAMD17-01-1-0358
- American Cancer Society. Grant Number: RPG-97-167-01-MGO
- Oklahoma Center for the Advancement of Science and Technology. Grant Numbers: AR05.1025, AR02.2032, AR99.2-007, AR01.1-050
- National Institutes of Health
- National Center for Research Resources
- General Clinical Research Center. Grant Number: M01RR-14467
- Presbyterian Health Foundation
- Oklahoma Life Sciences Fund
- Swisher Family Trust
- age-specific genetic associations;
- steroid hormone pathway;
- single nucleotide polymorphisms;
- breast cancer
Breast cancer (BC) is a complex disease, and the incidence rates for BC increase with age. Both environmental factors and genetics have an impact on the risk of BC. Although the effects of environmental factors may vary with age, it has been assumed generally that the penetrance of single nucleotide polymorphisms (SNPs) is constant throughout life. In the current study, the results demonstrated that certain SNPs exhibit BC risk associations that vary considerably with age.
SNPs in 12 steroid hormone pathway genes were investigated for associations with BC risk in white women who were enrolled in an age-matched, case-control (1:2 for cases and controls, respectively) study that consisted of a discovery set (n = 5000 women) and an independent validation set (n = 1583 women).
Significant age-related trends were identified and confirmed for SNPs in 4 genes associated with BC risk. The cytosine/cytosine (C/C) genotype of cytochrome P450 XIB2 (CYP11B2) was associated with decreased risk at younger ages (ages 30–44 years) but an increased risk at older ages (ages 55–69 years). The homozygous cytosine-guanine (CG/CG) genotype of uridine phosphorylase glycosyltransferase 1A7 (UGT1A7) was associated with increased risk at younger ages but decreased risk at older ages. Associations in cytochrome P450 19 (CYP19) and progesterone receptor (PGR) were confined to middle age (ages 45–54 years).
The identification of age-specific genetic associations may have profound implications for future etiologic studies of BC and for the use of SNP genotyping to accurately predict the risk of BC in women. Cancer 2007. © 2007 American Cancer Society.