Journal Article

The joint effect of smoking and <i>AIB1</i> on breast cancer risk in <i>BRCA1</i> mutation carriers

Susan Colilla, Philip W. Kantoff, Susan L. Neuhausen, Andrew K. Godwin, Mary B. Daly, Steven A. Narod, Judy E. Garber, Henry T. Lynch, Myles Brown, Barbara L. Weber and Timothy R. Rebbeck

in Carcinogenesis

Volume 27, issue 3, pages 599-605
Published in print March 2006 | ISSN: 0143-3334
Published online October 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi246

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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.

Keywords: BRCA1, breast cancer susceptibility gene 1; CI, confidence interval; ER, estrogen receptor; df, degrees of freedom; HR, hazard ratio; SNPs, single nucleotide polymorphisms

Journal Article.  6114 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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