title: Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort study.
abstract: Repeat length of the CAG microsatellite polymorphism in exon 1 of the androgen receptor (AR) gene has been associated with risk of prostate cancer in humans. This association has been the focus of >20 primary epidemiological publications and multiple review articles, but a consistent and reproducible association has yet to be confirmed. We systematically addressed possible causes of false-negative and false-positive association in >4,000 individuals from a multiethnic, prospective cohort study of prostate cancer, comprehensively studying genetic variation by microsatellite genotyping, direct resequencing of exons in advanced cancer cases, and haplotype analysis across the 180-kb AR genomic locus. These data failed to confirm that common genetic variation in the AR gene locus influences risk of prostate cancer. A systematic approach that assesses both coding and noncoding genetic variation in large and diverse patient samples can help clarify hypotheses about association between genetic variants and disease.
authors.affiliation: Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Freedman
authors.forename: Celeste L
authors.initials: CL
authors.lastname: Pearce
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
mesh_terms: D000368:Aged; D001483:Base Sequence; D015331:Cohort Studies; D005006:Ethnicity; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D012306:Risk
chemical_list: D011944:Receptors, Androgen