Breast Density Strongly Genetic; Cancer Risk Not Restricted to Dense Tissue
Having dense breast tissue, a risk factor for breast cancer, is highly genetic, which may partially explain the familial aggregation of breast cancer, Swedish researchers report.
Mammographic density is a strong heritable trait, but data on its genetic component are limited to either qualitative or semi-automated area-based measures, they explain in a paper online November 5 in the Journal of the National Cancer Institute The key disadvantage of these measures it that they are reader-dependent and do not acknowledge the 3D structure of the breast.
Dr. Judith Brand from Karolinska Institutet in Stockholm and colleagues studied the heritability of volumetric mammographic density using fully automated measures and explored the shared genetic component with breast cancer susceptibility loci.
The heritability analysis included 955 sib-pairs (908 full-sib and 47 half-sib pairs) and the genetic analysis included more than 4,000 unrelated women.
They observed “high heritability” values for volumetric mammographic density, although estimates were weaker for absolute than percent dense volume.
After multivariate adjustment, the heritability estimate for percent dense volume was 0.63; it was 0.43 for absolute dense volume and 0.61 for absolute nondense volume (all p<0.001).
In the genetic analysis, the researchers replicated previously reported associations with the single nucleotide polymorphisms (SNPs) rs10995190 (ZNF365) and rs2046210 (ESR1) with mammographic density.
They also identified novel associations with breast cancer SNPs at 6q25: rs9485372 (TAB2) and rs9383938 (ESR1).
The researchers also found evidence linking breast cancer SNPs rs6001930 (MKL1) and rs17356907 (NTN4) with the absolute volume of nondense tissue. This shows that the shared genetic component with breast cancer is not restricted to dense tissue only, they say.
NEW YORK (Reuters Health) J Natl Cancer Inst 2014.