title: Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort.
abstract: BACKGROUND
  Mammographic density is a strong risk factor for breast cancer. Our objective was to examine its association with polymorphisms identifying breast cancer susceptibility loci that were ascertained in recent genome-wide association studies.
  
  
  METHODS
  Subjects were 825 women who participated in previous case-control studies of mammographic density and genetic factors nested within the Multiethnic Cohort study and were from three ethnic groups (White, Japanese American, Native Hawaiian). Eight polymorphisms (rs2981582 in FGFR2, rs3803662 and rs12443621in TOX3, rs3817198 in LSP1, rs981782 and rs10941679 near HCN1/MRPS30, rs889312 in MAP3K1, and rs13387042 at 2q) were examined. Mammographic density was quantified with a computer-assisted method as the percent dense area: the area of radiologically dense fibroglandular tissue relative to the total breast area that also includes radiologically lucent fatty tissue.
  
  
  RESULTS
  The polymorphism rs12443621 in TOX3 was associated with percent dense area; women with at least one G allele (previously associated with increased breast cancer risk) had 3% to 4% higher densities than women with two A alleles. The polymorphism rs10941679 near HCN1/MRPS30 was also associated with percent dense area; women who were homozygous for the G allele (previously associated with increased breast cancer risk) had 4% to 5% lower densities than women with at least one A allele. The other polymorphisms were not associated with percent dense area.
  
  
  CONCLUSIONS
  The available data suggest that the effects of most of these polymorphisms on breast cancer are not mediated by mammographic density. Some effects may have been too small to be detected. The association with rs12443621 may provide clues as to how variation in TOX3 influences breast cancer risk.
authors.affiliation: Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Honolulu, HI 96813, USA. cwoolcott@crch.hawaii.edu
authors.forename: Christy G
authors.initials: CG
authors.lastname: Woolcott
authors.forename: Gertraud
authors.initials: G
authors.lastname: Maskarinec
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Martijn
authors.initials: M
authors.lastname: Verheus
authors.forename: Ian S
authors.initials: IS
authors.lastname: Pagano
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008327:Mammography / Q000379:methods*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins