Carcinogenesis Advance Access published online on December 6, 2005
Carcinogenesis, doi:10.1093/carcin/bgi294
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1 University of North Carolina, School of Public Health, Department of Epidemiology, Chapel Hill, NC
* To whom correspondence should be addressed. Insulin-like growth factor I (IGF-I) is an important regulator of growth and differentiation and is a potent mitogen for human breast cancer cells. Recent investigations suggest an association between cytosine-adenine dinucleotide (CA)n repeat polymorphisms of the IGF1 gene and IGF-I levels and further evidence indicates that genotype may influence breast cancer risk. We assessed the relation between IGF1 (CA)n repeats and breast cancer and evaluated modification of genotype effects according to traditional breast cancer risk factors in 1,028 breast cancer cases and 1,086 controls. An increased risk of breast cancer was seen for genotypes that included alleles with fewer than (CA)19 repeats when compared to (CA)19 repeat carriers, an association that was particularly strong among premenopausal women (odds ratio (OR) = 3.31; 95% confidence interval (CI) = 1.47, 7.48). No significant association was observed between an IGF1 genotype with no (CA)19 repeat compared to (CA)19 repeat genotypes in either pre- or postmenopausal women overall. However when traditional breast cancer risk factors were considered, premenopausal women with genotypes that lacked a (CA)19 repeat had a nearly 60% increased risk of breast cancer among those who had ever used hormonal birth control, while never users had a significantly reduced risk (Pinteraction = 0.01). Among postmenopausal women, those with genotypes lacking a (CA)19 repeat allele had significantly increased breast cancer risk among subjects with a lower than median BMI (OR = 1.77 95% CI = 1.09, 2.87), while no association for IGF1 genotype was seen among women with a higher than median BMI (Pinteraction = 0.04). Our results demonstrate a role for alleles with fewer than (CA)19 repeats as a risk factor for breast cancer and also suggest that several traditional breast cancer risk factors modify the association of the IGF1 (CA)19 repeat genotype.
Received September 26, 2005
Revised November 14, 2005
Accepted November 15, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
IGF1 CA repeat polymorphisms, lifestyle factors and breast cancer risk in the Long Island Breast Cancer Study Project
Rebecca J. Cleveland 1 *,
Marilie D. Gammon 1,
Sharon N. Edmiston 2,
Susan L. Teitelbaum 3,
Julie A. Britton 3,
Mary Beth Terry 4,
Sybil M. Eng 5,
Alfred I. Neugut 6,
Regina M. Santella 7,
and
Kathleen Conway 8
2 University of North Carolina, School of Medicine, Lineberger Comprehensive Cancer Center, Chapel Hill, NC
3 Mt. Sinai School of Medicine, Department of Community and Preventive Medicine, New York, NY
4 Columbia University, Mailman School of Public Health, Department of Epidemiology, New York, NY
5 Pfizer, Inc., Global Epidemiology, Safety, and Risk Management, New York, NY
6 Columbia University, Mailman School of Public Health, Department of Epidemiology, New York, NY; Columbia University, College of Physicians and Surgeons, Department of Medicine, New York, NY
7 Columbia University, Mailman School of Public Health, Department of Environmental Health Sciences, New York, NY
8 University of North Carolina, School of Public Health, Department of Epidemiology, Chapel Hill, NC; University of North Carolina, School of Medicine, Lineberger Comprehensive Cancer Center, Chapel Hill, NC
Rebecca J. Cleveland, E-mail: becki{at}unc.edu
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