BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Breast density and sex hormones can be considered as independent sets of traits. IMPACT: Breast density and sex hormones can be used as intermediate phenotypes in the search for breast cancer susceptibility loci.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Breast density and sex hormones can be considered as independent sets of traits. IMPACT: Breast density and sex hormones can be used as intermediate phenotypes in the search for breast cancer susceptibility loci.
Authors: Shelley S Tworoger; Xuehong Zhang; A Heather Eliassen; Jing Qian; Graham A Colditz; Walter C Willett; Bernard A Rosner; Peter Kraft; Susan E Hankinson Journal: J Clin Oncol Date: 2014-08-18 Impact factor: 44.544
Authors: Celine M Vachon; Vera J Suman; Kathleen R Brandt; Matthew L Kosel; Aman U Buzdar; Janet E Olson; Fang-Fang Wu; Lynn M Flickinger; Giske Ursin; Catherine R Elliott; Lois Shepherd; Richard M Weinshilboum; Paul E Goss; James N Ingle Journal: Clin Cancer Res Date: 2013-03-06 Impact factor: 12.531
Authors: N L Henry; H-P Chan; J Dantzer; C P Goswami; L Li; T C Skaar; J M Rae; Z Desta; N Khouri; R Pinsky; S Oesterreich; C Zhou; L Hadjiiski; S Philips; J Robarge; A T Nguyen; A M Storniolo; D A Flockhart; D F Hayes; M A Helvie; V Stearns Journal: Br J Cancer Date: 2013-10-01 Impact factor: 7.640
Authors: Deborah J Thompson; Tracy A O'Mara; Dylan M Glubb; Jodie N Painter; Timothy Cheng; Elizabeth Folkerd; Deborah Doody; Joe Dennis; Penelope M Webb; Maggie Gorman; Lynn Martin; Shirley Hodgson; Kyriaki Michailidou; Jonathan P Tyrer; Mel J Maranian; Per Hall; Kamila Czene; Hatef Darabi; Jingmei Li; Peter A Fasching; Alexander Hein; Matthias W Beckmann; Arif B Ekici; Thilo Dörk; Peter Hillemanns; Matthias Dürst; Ingo Runnebaum; Hui Zhao; Jeroen Depreeuw; Stefanie Schrauwen; Frederic Amant; Ellen L Goode; Brooke L Fridley; Sean C Dowdy; Stacey J Winham; Helga B Salvesen; Jone Trovik; Tormund S Njolstad; Henrica M J Werner; Katie Ashton; Tony Proietto; Geoffrey Otton; Luis Carvajal-Carmona; Emma Tham; Tao Liu; Miriam Mints; Rodney J Scott; Mark McEvoy; John Attia; Elizabeth G Holliday; Grant W Montgomery; Nicholas G Martin; Dale R Nyholt; Anjali K Henders; John L Hopper; Nadia Traficante; Matthias Ruebner; Anthony J Swerdlow; Barbara Burwinkel; Hermann Brenner; Alfons Meindl; Hiltrud Brauch; Annika Lindblom; Diether Lambrechts; Jenny Chang-Claude; Fergus J Couch; Graham G Giles; Vessela N Kristensen; Angela Cox; Manjeet K Bolla; Qin Wang; Stig E Bojesen; Mitul Shah; Robert Luben; Kay-Tee Khaw; Paul D P Pharoah; Alison M Dunning; Ian Tomlinson; Mitch Dowsett; Douglas F Easton; Amanda B Spurdle Journal: Endocr Relat Cancer Date: 2015-11-16 Impact factor: 5.678