Carcinogenesis Advance Access originally published online on October 22, 2005
Carcinogenesis 2006 27(3):599-605; doi:10.1093/carcin/bgi246
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers
Department of Biostatistics and Epidemiology and 1 Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA, 2 Department of Medical Oncology and 3 Lank Center for Genitourinary Cancer, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA, 4 Division of Epidemiology, Department of Medicine, University of California Irvine, Irvine, CA, USA, 5 Fox Chase Cancer Center, Philadelphia, PA 19111, USA, 6 Women's College Hospital, Toronto, ON M5G 1N8, Canada and 7 Department of Preventive Medicine, Creighton University, Omaha, NE 68179, USA
* To whom correspondence should be addressed at: Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Room no. 916, 423 Guardian Drive, Philadelphia, PA 19104, USA. Tel: +1 215 746 0370; Fax: +1 215 573 2265; Email: scolilla{at}cceb.med.upenn.edu
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 polyglutamine 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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Miremadi, M. Z. Oestergaard, P. D.P. Pharoah, and C. Caldas Cancer genetics of epigenetic genes Hum. Mol. Genet., April 15, 2007; 16(R1): R28 - R49. [Abstract] [Full Text] [PDF]
|
|