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Eur J Cancer. 2013 Jan;49(2):474-81. doi: 10.1016/j.ejca.2012.08.026. Epub 2012 Sep 27.

Association analysis between breast cancer genetic variants and mammographic density in a large population-based study (Determinants of Density in Mammographies in Spain) identifies susceptibility loci in TOX3 gene.

Author information

1
National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain. pfernandezn@isciii.es

Abstract

BACKGROUND:

Mammographic density (MD) is regarded as an intermediate phenotype in breast cancer development. This association study investigated the influence of 14 breast cancer susceptibility loci identified through previous genome-wide association studies on MD among the participants in the "Determinants of Density in Mammographies in Spain" (DDM-Spain) study.

METHODS:

Our study covered a total of 3348 Caucasian women aged 45-68years, recruited from seven Spanish breast cancer screening centres having DNA available. Mammographic density was blindly assessed by a single reader using a semiquantitative scale. Ordinal logistic models, adjusted for age, body mass index and menopausal status, were used to estimate the association between each genotype and MD.

RESULTS:

Evidence of association with MD was found for variant rs3803662 (TOX3) (Odds Ratio (OR)=1.13, 95% Confidence Interval (CI)=1.03-1.25), and marginal evidence of association for susceptibility loci rs3817198 (LSP1) (OR=1.09, 95% CI=1.00-1.20) and rs2981582 (FGFR2) (OR=0.92, 95% CI=0.84-1.01). Two other loci were associated with MD solely among pre-menopausal women, namely, rs4973768 (SLC4A7) (OR=0.83, 95% CI=0.70-1.00) and rs4415084 (MEPS30) (OR=1.22, 95% CI=1.00-1.49).

CONCLUSIONS:

Our findings lend some support to the hypothesis which links these susceptibility loci to MD.

PMID:
23021931
DOI:
10.1016/j.ejca.2012.08.026
[Indexed for MEDLINE]

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