Breast cancer susceptibility loci and mammographic density

Rulla M. Tamimi, David Cox, Peter Kraft, Graham A. Colditz, Susan E. Hankinson, David J. Hunter

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Abstract

Introduction: Recently, the Breast Cancer Association Consortium (BCAC) conducted a multi-stage genome-wide association study and identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Given the high degree of heritability of mammographic density and its strong association with breast cancer, it was hypothesised that breast cancer susceptibility loci may also be associated with breast density and provide insight into the biology of breast density and how it influences breast cancer risk.Methods: We conducted an analysis in the Nurses' Health Study (n = 1121) to assess the relation between 11 breast cancer susceptibility loci and mammographic density. At the time of their mammogram, 217 women were premenopausal and 904 women were postmenopausal. We used generalised linear models adjusted for covariates to determine the mean percentage of breast density according to genotype.Results: Overall, no association between the 11 breast cancer susceptibility loci and mammographic density was seen. Among the premenopausal women, three SNPs (rs12443621 [TNRc9/LOC643714], rs3817198 [lymphocyte-specific protein-1] and rs4666451) were marginally associated with mammographic density (p < 0.10). All three of these SNPs showed an association that was consistent with the direction in which these alleles influence breast cancer risk. The difference in mean percentage mammographic density comparing homozygous wildtypes to homozygous variants ranged from 6.3 to 8.0%. None of the 11 breast cancer loci were associated with postmenopausal breast density.Conclusion: Overall, breast cancer susceptibility loci identified through a genome-wide association study do not appear to be associated with breast cancer risk.

Original languageEnglish
Article numberR66
JournalBreast Cancer Research
Volume10
Issue number4
DOIs
StatePublished - Aug 5 2008

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    Tamimi, R. M., Cox, D., Kraft, P., Colditz, G. A., Hankinson, S. E., & Hunter, D. J. (2008). Breast cancer susceptibility loci and mammographic density. Breast Cancer Research, 10(4), [R66]. https://doi.org/10.1186/bcr2127