Abstract
Mammographic breast density and endogenous sex-hormone levels are both strong risk factors for breast cancer. This study investigated whether there is evidence for a shared genetic basis between these risk factors. Using data on 1,286 women from 617 families, we estimated the heritabilities of serum estradiol, testosterone, and sex-hormone binding globulin (SHBG) levels and of three measures of breast density (dense area, nondense area, and percentage density). We tested for associations between hormone levels and density measures and estimated the genetic and environmental correlations between pairs of traits using variance and covariance components models and pedigree-based maximum likelihood methods. We found no significant associations between estradiol, testosterone, or SHBG levels and any of the three density measures, after adjusting for body mass index (BMI). The estimated heritabilities were 63%, 66%, and 65% for square root-transformed adjusted percentage density, dense area, and nondense area, respectively, and 40%, 25%, and 58% for log-transformed-adjusted estradiol, testosterone, and SHBG. We found no evidence of a shared genetic basis between any hormone levels and any measure of density, after adjusting for BMI. The negative genetic correlation between dense and nondense areas remained significant even after adjustment for BMI and other covariates (ρ = -0.34; SE = 0.08; P = 0.0005). Breast density and sex hormones can be considered as independent sets of traits. Breast density and sex hormones can be used as intermediate phenotypes in the search for breast cancer susceptibility loci.
Highlights
Higher circulating estradiol (E2) and testosterone (T) levels are known to increase the risk of postmenopausal breast cancer, whereas risk is inversely related to the levels of sex-hormone binding globulin (SHBG), which binds estradiol and testosterone with high affinity, effectively limiting their bioavailability [1,2,3]
Eleven women included in the heritability estimation of density measures reported using hormone replacement therapy (HRT)
In our cross-sectional study of 682 postmenopausal women, we found no strong associations between estradiol, testosterone, and SHBG levels and any of the 3 density measures, after adjusting for adiposity (BMI), in line with most, but not all, of the previous studies in this area [31,32,33,34,35,36,37,38]
Summary
Higher circulating estradiol (E2) and testosterone (T) levels are known to increase the risk of postmenopausal breast cancer, whereas risk is inversely related to the levels of sex-hormone binding globulin (SHBG), which binds estradiol and testosterone with high affinity, effectively limiting their bioavailability [1,2,3]. It has Authors' Affiliations: 1Department of Public Heath and Primary Care, Centre for Cancer Genetic Epidemiology; 2Department of Radiology, Addenbrooke's NHS Foundation Trust, University of Cambridge, Cambridge; 3Plastic Surgery Unit, Royal Free Hospital; and 4Academic Department of Biochemistry, Royal Marsden Hospital, London, United Kingdom. This study investigated whether there is evidence for a shared genetic basis between these risk factors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
