Genetic variants associated with breast size also influence breast

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.

Discovery and Characterization of Cancer Genetic Susceptibility Alleles

Biomedicines, Free Full-Text

Healthy Breasts: A Guide to Caring for Your Breasts - HealthyWomen

Frontiers Association between breast cancer and thyroid cancer risk: a two-sample Mendelian randomization study

Frontiers Genetics, epigenetics and transgenerational transmission of obesity in children

A Twin Study of Breastfeeding With a Preliminary Genome-Wide Association Scan, Twin Research and Human Genetics

Medicina, Free Full-Text

In silico analysis of nsSNPs in ABCB1 gene affecting breast cancer associated protein P-glycoprotein (P-gp) - ScienceDirect

Genetics of Breast and Gynecologic Cancers (PDQ®) - NCI

Stereotypical and Actual Associations of Breast Size with Mating-Relevant Traits

Average Breast Size: Are Age, Height, and Weight a Factor?

The Genetics of Cancer - NCI

What are the determinants of breast size differences across countries? - Quora

Identification of breast cancer associated variants that modulate transcription factor binding

The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant