Genetic variants associated with breast size also influence breast cancer risk

BMC Medical Genetics

Research Article

Nicholas Eriksson¹  Joyce Y Tung¹  David A Hinds¹  Chuong B Do¹  Geoffrey M Benton¹  Uta Francke¹  Amy K Kiefer¹  Joanna L Mountain¹ 

[1] 23andMe, Inc, 94043, Mountain View, CA, USA;

关键词: Breast Cancer;    Breast Cancer Risk;    Mammographic Density;    Breast Density;    Inhibin;   

DOI  :  10.1186/1471-2350-13-53

 received in 2011-12-14, accepted in 2012-06-30,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundWhile some factors of breast morphology, such as density, are directly implicated in breast cancer, the relationship between breast size and cancer is less clear. Breast size is moderately heritable, yet the genetic variants leading to differences in breast size have not been identified.MethodsTo investigate the genetic factors underlying breast size, we conducted a genome-wide association study (GWAS) of self-reported bra cup size, controlling for age, genetic ancestry, breast surgeries, pregnancy history and bra band size, in a cohort of 16,175 women of European ancestry.ResultsWe identified seven single-nucleotide polymorphisms (SNPs) significantly associated with breast size (p<5·10−8): rs7816345 near ZNF703, rs4849887 and (independently) rs17625845 flanking INHBB, rs12173570 near ESR1, rs7089814 in ZNF365, rs12371778 near PTHLH, and rs62314947 near AREG. Two of these seven SNPs are in linkage disequilibrium (LD) with SNPs associated with breast cancer (those near ESR1 and PTHLH), and a third (ZNF365) is near, but not in LD with, a breast cancer SNP. The other three loci (ZNF703, INHBB, and AREG) have strong links to breast cancer, estrogen regulation, and breast development.ConclusionsThese results provide insight into the genetic factors underlying normal breast development and show that some of these factors are shared with breast cancer. While these results do not directly support any possible epidemiological relationships between breast size and cancer, this study may contribute to a better understanding of the subtle interactions between breast morphology and breast cancer risk.

【 授权许可】

CC BY   
© Eriksson et al.; licensee BioMed Central Ltd. 2012