title: Vitamin D receptor polymorphisms and breast cancer risk in a high-incidence population: a pilot study.
abstract: BACKGROUND
  Marin County, CA has very high incidence of breast cancer. Traditional risk factors, such as those included in the Gail model, do not effectively stratify breast cancer in this population. This retrospective case-control pilot study evaluates DNA from volunteers from a previous Marin County breast cancer epidemiology study. A polyfactorial risk model (OncoVue; InterGenetics Incorporated) that incorporates 22 polymorphisms in 19 genes and 5 clinical risk factors was used to stratify risk in Marin County women.
  
  
  METHODS
  DNA genotyping was performed on 164 Caucasian women diagnosed with primary breast cancer in Marin County from 1997 to 1999 and 174 age- and ethnicity-matched control subjects. Individual lifetime risks were determined using the polyfactorial risk model and genotype frequencies in women at elevated risk were compared with the overall genotypes.
  
  
  RESULTS
  The vitamin D receptor VDR ApaI A2/A2 (rs7975232) homozygous polymorphism was present in high frequency in elevated-risk women. Sixty-four percent of elevated-risk women had the VDR Apa1 A2/A2 genotype compared with only 34% in the overall study, a statistically significant 1.9-fold difference (p = 0.0003). VDR Apa1 A2/a1 and a1/a1 genotypes were also present, but in lower frequencies.
  
  
  CONCLUSIONS
  The high frequency of the VDR Apa1 A2/A2 homozygous polymorphism in women designated as elevated risk for breast cancer by the polyfactorial risk model might be related to the high incidence rates of breast cancer in Marin County, CA. Vitamin D supplementation could modify risk of breast cancer in this population.
authors.affiliation: Surgeon Scientist, Point Reyes Station, CA 94956, USA. kdalessandri@gmail.com
authors.forename: Kathie M
authors.initials: KM
authors.lastname: Dalessandri
authors.forename: Rei
authors.initials: R
authors.lastname: Miike
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.forename: Georgianna
authors.initials: G
authors.lastname: Farren
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Pugh
authors.forename: Sharmila
authors.initials: S
authors.lastname: Manjeshwar
authors.forename: Daniele C
authors.initials: DC
authors.lastname: DeFreese
authors.forename: Eldon R
authors.initials: ER
authors.lastname: Jupe
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program
chemical_list: D005819:Genetic Markers; D018167:Receptors, Calcitriol