1. 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
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Javier Benitez, Guillermo Pita, Francisca Collado-García, María Moreno, Belen Herraez, Carmen Santamariña, Francisco Casanova, Anna González-Neira, Nieves Ascunce, Pablo Fernández-Navarro, Josefa Miranda-García, Marina Pollán, and Carmen Vidal
- Subjects
Cancer Research ,Genotype ,Large population ,Breast Neoplasms ,Biology ,Polymorphism, Single Nucleotide ,Breast cancer ,Risk Factors ,Polymorphism (computer science) ,medicine ,Humans ,Genetic Predisposition to Disease ,Mammary Glands, Human ,Gene ,Breast Density ,Genetic association ,Genetics ,High Mobility Group Proteins ,MAMMOGRAPHIC DENSITY ,Genetic Variation ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Oncology ,TOX3 ,Spain ,Trans-Activators ,Susceptibility locus ,Female ,Apoptosis Regulatory Proteins ,Receptors, Progesterone ,Genome-Wide Association Study - Abstract
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.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.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).Our findings lend some support to the hypothesis which links these susceptibility loci to MD.
- Published
- 2013