Genetic variants associated with breast size also influence breast cancer risk

• Main Authors: Eriksson Nicholas, Benton Geoffrey M, Do Chuong B, Kiefer Amy K, Mountain Joanna L, Hinds David A, Francke Uta, Tung Joyce Y
• Format: Article
• Language: English
• Published: BMC 2012-06-01
• Series: BMC Medical Genetics
• Online Access: http://www.biomedcentral.com/1471-2350/13/53

<p>Abstract</p> <p>Background</p> <p>While 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.</p> <p>Methods</p> <p>To 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.</p> <p>Results</p> <p>We identified seven single-nucleotide polymorphisms (SNPs) significantly associated with breast size (<it>p</it><5·10⁻⁸): rs7816345 near <it>ZNF703</it>, rs4849887 and (independently) rs17625845 flanking <it>INHBB</it>, rs12173570 near <it>ESR1</it>, rs7089814 in <it>ZNF365</it>, rs12371778 near <it>PTHLH</it>, and rs62314947 near <it>AREG</it>. Two of these seven SNPs are in linkage disequilibrium (LD) with SNPs associated with breast cancer (those near <it>ESR1</it> and <it>PTHLH</it>), and a third (<it>ZNF365</it>) is near, but not in LD with, a breast cancer SNP. The other three loci (<it>ZNF703</it>, <it>INHBB</it>, and <it>AREG</it>) have strong links to breast cancer, estrogen regulation, and breast development.</p> <p>Conclusions</p> <p>These 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.</p>