title: Genetic determinants of mammographic density.
abstract: BACKGROUND
  Changes in breast density are highly correlated with steroid hormone exposure.
  
  
  METHODS
  In a cross-sectional study of 396 Caucasian and African-American women, we evaluated whether polymorphisms in genes involved in steroid hormone biosynthesis and metabolism, CYP17 (T27C), COMT (Val158Met), 17HSDB1 (Ser312Gly) and 3HSDB1 (Asn367Thr), predict mammographic density. We also evaluated whether associations vary by menopausal and hormone replacement therapy status.
  
  
  RESULTS
  We found no strong consistent relationships between polymorphisms in these genes and breast density. African-American women homozygous for the Thr allele of 3HSDB1 had increased density (the absolute difference versus the Asn/Asn genotype was +19.7%; P trend = 0.02), while Caucasian homozygous women had decreased density (-5.1%; P trend = 0.04). Among premenopausal women, carriers of the Ser allele had (not significantly) greater density (versus Gly/Gly genotype: +7.1%; P trend = 0.07). In addition, among current users of hormone replacement therapy, we observed that women with the low-activity Met/Met genotype of COMT had greater breast density (versus the Val/Val genotype: +11.7%; P trend = 0.01).
  
  
  CONCLUSIONS
  Additional large studies evaluating these and other candidate breast cancer genes will be required to determine what proportion, if any, of the interindividual differences in breast density are due to underlying genetic variation in genes involved in steroid hormone biosynthesis or metabolism.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA. haiman@usc.edu
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: David
authors.initials: D
authors.lastname: Berg
authors.forename: Sue A
authors.initials: SA
authors.lastname: Ingles
authors.forename: Martine
authors.initials: M
authors.lastname: Salane
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D044383:Black People / Q000235:genetics*; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D006728:Hormones / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008327:Mammography; D008780:Methyltransferases / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D006728:Hormones; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D008780:Methyltransferases; D002394:Catechol O-Methyltransferase