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Genetic Variants Associated With Breast Size Also Influence Breast Cancer Risk


Genetic Variants Associated With Breast Size Also Influence Breast Cancer Risk

Nicholas Eriksson et al. BMC Med Genet.


Background: 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.

Methods: 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.

Results: We 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.

Conclusions: 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.


Figure 1
Figure 1
Manhattan plot of association with breast size.log10p-values across all SNPs tested. SNPs shown in red are genome-wide significant (p<5·10−8). Regions are named with the postulated candidate gene.
Figure 2
Figure 2
Associations with breast size in six regions with genome-wide significant SNPs. Colors depict the squared correlation (r2) of each SNP with the most associated SNP (which is shown in purple). Gray indicates SNPs for which r2 information was missing. For the plot labeled with rs7816345, the gene ZNF703 lies about 400kb outside the region displayed.

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