title: Breast cancer susceptibility variants and mammographic density phenotypes in norwegian postmenopausal women.
abstract: BACKGROUND
  Mammographic density (MD) is one of the strongest known breast cancer risk factors. Twin studies have suggested that a large part of the variation in MD is genetically determined. We hypothesized that breast cancer susceptibility variants may affect MD, and that their effects may be modified by nongenetic factors.
  
  
  METHODS
  We assessed MD, using a computer-assisted method, on 2,348 postmenopausal Caucasian women (50-69 years) who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004 or 2006-07. We used linear regression (additive models) to determine the association between each SNP and MD, adjusting for age, body mass index (BMI), and study. We evaluated MD associations with 17 established breast cancer SNPs, overall, and by strata defined by non-genetic factors.
  
  
  RESULTS
  Two variants, 6q25.1-rs9383938 and TXNRD2-rs8141691, were statistically significantly associated with percent MD (P = 0.019 and 0.03, respectively), with the 6q25.1-rs9383938 association being consistent with the SNP effect on breast cancer risk. The effect of 6q25.1-rs3734805 on percent MD varied between parous and nulliparous women (Pinteraction = 0.02), whereas the effects of 9q31.2-rs865686 and MRPS30:FGF10-rs4415084 differed across strata of BMI (Pinteraction = 0.01 and 0.005, respectively). There was no evidence of effect modification by estrogen and progestin therapy use or alcohol consumption.
  
  
  CONCLUSIONS
  This study provides novel evidence of shared genetic risk factors between MD and breast cancer and of possible MD genetic-environmental interactions.
  
  
  CONCLUSIONS
  Although the results may be chance findings, they nevertheless highlight the need to investigate interactions with nongenetic factors in studies on the genetics of MD.
authors.affiliation: University of Oslo, Oslo, Norway.
authors.forename: Merete
authors.initials: M
authors.lastname: Ellingjord-Dale
authors.affiliation: Cancer Registry of Norway, Oslo, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Grotmol
authors.affiliation: University of Southern California, Los Angeles, California.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.affiliation: University of Southern California, Los Angeles, California.
authors.forename: David J
authors.initials: DJ
authors.lastname: Van Den Berg
authors.affiliation: Cancer Registry of Norway, Oslo, Norway.
authors.forename: Solveig
authors.initials: S
authors.lastname: Hofvind
authors.affiliation: Norwegian Knowledge Centre for the Health Services, Health Economic and Drug Unit, Oslo, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Couto
authors.affiliation: University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ulla
authors.initials: U
authors.lastname: Sovio
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Isabel
authors.initials: I
authors.lastname: Dos-Santos-Silva
authors.affiliation: University of Oslo, Oslo, Norway. Cancer Registry of Norway, Oslo, Norway. Giske.Ursin@kreftregisteret.no.
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
mesh_terms: D000368:Aged; D000071060:Breast Density; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D004198:Disease Susceptibility; D055088:Early Detection of Cancer; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities* / Q000473:pathology; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics; D012307:Risk Factors