TY - JOUR
T1 - Is mammographic breast density an endophenotype for breast cancer?
AU - Darcey, Ellie
AU - McCarthy, Nina
AU - Moses, Eric
AU - Saunders, Christobel
AU - Cadby, Gemma
AU - Stone, Jennifer
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Mammographic breast density (MBD) is a strong and highly heritable predictor of breast cancer risk and a biomarker for the disease. This study systematically assesses MBD as an endopheno-type for breast cancer—a quantitative trait that is heritable and genetically correlated with disease risk. Using data from the family-based kConFab Study and the 1994/1995 cross-sectional Busselton Health Study, participants were divided into three status groups—cases, relatives of cases and controls. Participant’s mammograms were used to measure absolute dense area (DA) and percentage dense area (PDA). To address each endophenotype criterion, linear mixed models and heritability analysis were conducted. Both measures of MBD were significantly associated with breast cancer risk in two independent samples. These measures were also highly heritable. Meta-analyses of both studies showed that MBD measures were higher in cases compared to relatives (β = 0.48, 95% CI = 0.10, 0.86 and β = 0.41, 95% CI = 0.06, 0.78 for DA and PDA, respectively) and in relatives compared to controls (β = 0.16, 95% CI = −0.24, 0.56 and β = 0.16, 95% CI = −0.21, 0.53 for DA and PDA, respectively). This study formally demonstrates, for the first time, that MBD is an endophenotype for breast cancer.
AB - Mammographic breast density (MBD) is a strong and highly heritable predictor of breast cancer risk and a biomarker for the disease. This study systematically assesses MBD as an endopheno-type for breast cancer—a quantitative trait that is heritable and genetically correlated with disease risk. Using data from the family-based kConFab Study and the 1994/1995 cross-sectional Busselton Health Study, participants were divided into three status groups—cases, relatives of cases and controls. Participant’s mammograms were used to measure absolute dense area (DA) and percentage dense area (PDA). To address each endophenotype criterion, linear mixed models and heritability analysis were conducted. Both measures of MBD were significantly associated with breast cancer risk in two independent samples. These measures were also highly heritable. Meta-analyses of both studies showed that MBD measures were higher in cases compared to relatives (β = 0.48, 95% CI = 0.10, 0.86 and β = 0.41, 95% CI = 0.06, 0.78 for DA and PDA, respectively) and in relatives compared to controls (β = 0.16, 95% CI = −0.24, 0.56 and β = 0.16, 95% CI = −0.21, 0.53 for DA and PDA, respectively). This study formally demonstrates, for the first time, that MBD is an endophenotype for breast cancer.
KW - Breast cancer
KW - Endophenotype
KW - mammographic breast density
KW - Risk factor
UR - http://www.scopus.com/inward/record.url?scp=85111642004&partnerID=8YFLogxK
U2 - 10.3390/cancers13153916
DO - 10.3390/cancers13153916
M3 - Article
C2 - 34359817
AN - SCOPUS:85111642004
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 15
M1 - 3916
ER -