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

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• 作者：Pablo Fernandez-Navarro^a ; ^b ; ^{pfernandezn@isciii.es} ; Guillermo Pita^c ; Carmen Santamariñ ; a^d ; Mar&#237 ; a Pilar Moreno^e ; Carmen Vidal^f ; Josefa Miranda-Garc&#237 ; a^g ; Nieves Ascunce^h ; ⁱ ; Francisco Casanova^j ; Francisca Collado-Garc&#237 ; a^k ; Belen Herrá ; ez^c ; Anna Gonzá ; lez-Neira^c ; Javier Ben&#237 ; tez^c ; ^l ; ^m ; Marina Pollá ; n^a ; ^b
• 关键词：Polymorphism ; Single nucleotide ; Breast cancer ; Mammographic density
• 刊名：European Journal of Cancer
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：49
• 期：2
• 页码：474-481
• 全文大小：205 K

文摘

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 45-68 years, 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.