title: Associations between breast density and a panel of single nucleotide polymorphisms linked to breast cancer risk: a cohort study with digital mammography.
abstract: BACKGROUND
  Breast density and single-nucleotide polymorphisms (SNPs) have both been associated with breast cancer risk. To determine the extent to which these two breast cancer risk factors are associated, we investigate the association between a panel of validated SNPs related to breast cancer and quantitative measures of mammographic density in a cohort of Caucasian and African-American women.
  
  
  METHODS
  In this IRB-approved, HIPAA-compliant study, we analyzed a screening population of 639 women (250 African American and 389 Caucasian) who were tested with a validated panel assay of 12 SNPs previously associated to breast cancer risk. Each woman underwent digital mammography as part of routine screening and all were interpreted as negative. Both absolute and percent estimates of area and volumetric density were quantified on a per-woman basis using validated software. Associations between the number of risk alleles in each SNP and the density measures were assessed through a race-stratified linear regression analysis, adjusted for age, BMI, and Gail lifetime risk.
  
  
  RESULTS
  The majority of SNPs were not found to be associated with any measure of breast density. SNP rs3817198 (in LSP1) was significantly associated with both absolute area (p = 0.004) and volumetric (p = 0.019) breast density in Caucasian women. In African-American women, SNPs rs3803662 (in TNRC9/TOX3) and rs4973768 (in NEK10) were significantly associated with absolute (p = 0.042) and percent (p = 0.028) volume density respectively.
  
  
  CONCLUSIONS
  The majority of SNPs investigated in our study were not found to be significantly associated with breast density, even when accounting for age, BMI, and Gail risk, suggesting that these two different risk factors contain potentially independent information regarding a woman's risk to develop breast cancer. Additionally, the few statistically significant associations between breast density and SNPs were different for Caucasian versus African American women. Larger prospective studies are warranted to validate our findings and determine potential implications for breast cancer risk assessment.
authors.affiliation: Department of Radiology, University of Pennsylvania Perelman School of Medicine, 3600 Market St. Ste 360, Philadelphia, PA, 19104, USA. brad.keller@uphs.upenn.edu.
authors.forename: Brad M
authors.initials: BM
authors.lastname: Keller
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA. amccarthy8@partners.org.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: McCarthy
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. jinboche@mail.med.upenn.edu.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA. karmstrong6@mgh.harvard.edu.
authors.forename: Katrina
authors.initials: K
authors.lastname: Armstrong
authors.affiliation: Department of Radiology, University of Pennsylvania Perelman School of Medicine, 3600 Market St. Ste 360, Philadelphia, PA, 19104, USA. emily.conant@uphs.upenn.edu.
authors.forename: Emily F
authors.initials: EF
authors.lastname: Conant
authors.affiliation: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. susan.domchek@uphs.upenn.edu.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.affiliation: Department of Radiology, University of Pennsylvania Perelman School of Medicine, 3600 Market St. Ste 360, Philadelphia, PA, 19104, USA. despina.kontos@uphs.upenn.edu.
authors.forename: Despina
authors.initials: D
authors.lastname: Kontos
mesh_terms: D000328:Adult; D001741:Black or African American; D000483:Alleles; D000071060:Breast Density; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008327:Mammography / Q000379:methods; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012307:Risk Factors; D044465:White People