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Carcinogenesis Advance Access published online on October 22, 2005
Carcinogenesis, doi:10.1093/carcin/bgi246
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received July 21, 2005
Revised August 9, 2005
Accepted October 12, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers

Susan Colilla 1*, Philip W. Kantoff 2, Susan L. Neuhausen 3, Andrew K. Godwin 4, Mary B. Daly 4, Steven A. Narod 5, Judy E. Garber 6, Henry T. Lynch 7, Myles Brown 6, Barbara L. Weber 8, and Timothy R. Rebbeck 1

1 Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
2 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215; Lank Center for Genitourinary Cancer, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215
3 Division of Epidemiology, Department of Medicine, University of California Irvine, Irvine, CA
4 Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
5 Women's College Hospital, Toronto, Ontario M5G 1N8
6 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215
7 Department of Preventive Medicine, Creighton University, Omaha, Nebraska 68179
8 Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

* To whom correspondence should be addressed.
Susan Colilla, E-mail: scolilla{at}cceb.med.upenn.edu


  Abstract

Women with BRCA1 mutations are at an elevated risk for breast cancer. AIB1 (NCOA3/SRC3) genotype and smoking may alter this risk. We examined the differences in breast cancer risk by AIB1 poly-glutamine repeat polymorphism and pre-diagnosis smoking habits for BRCA1 mutation carriers to determine if there was an interaction between smoking and AIB1 genotype. Multivariate Cox proportional hazards regression was used with 316 female BRCA1 mutation carriers to model breast cancer risk. Ever having smoked was associated with a decreased breast cancer risk (Hazard Ratio (HR): 0.63, 95% CI: 0.47, 0.87). A dose-response relationship between number of pack-years smoked and breast cancer risk was also found for women who smoked <20 pack years of cigarettes (HR: 0.72, 95% CI: 0.52, 1.00) and for women who smoked ≥ 20 pack years (HR: 0.41, 95% CI: 0.23, 0.71; p for trend = 0.0007). Women with a 28 repeat allele for AIB1 had a significantly reduced risk of breast cancer (HR=0.72, 95% CI: 0.51, 1.00). Women who smoked ≥20 pack-years with a 28 repeat allele had an even greater reduced risk of breast cancer (HR=0.19, 95% CI: 0.07, 0.54) compared to women who were never smokers with no 28 allele. Since AIB1 appears to modulate the effect of endogenous hormones via the estrogen receptor, and smoking affects circulating hormone levels, these results support evidence that steroid hormones play an important role in breast carcinogenesis in BRCA1 mutation carriers, and suggest mechanisms for developing novel cancer prevention strategies for BRCA1 mutation carriers.

Keywords: BRCA1; AIB1; smoking; breast cancer; women.
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