title: Association of prostate cancer risk variants with gene expression in normal and tumor tissue.
abstract: BACKGROUND
  Numerous germline genetic variants are associated with prostate cancer risk, but their biologic role is not well understood. One possibility is that these variants influence gene expression in prostate tissue. We therefore examined the association of prostate cancer risk variants with the expression of genes nearby and genome-wide.
  
  
  METHODS
  We generated mRNA expression data for 20,254 genes with the Affymetrix GeneChip Human Gene 1.0 ST microarray from normal prostate (N = 160) and prostate tumor (N = 264) tissue from participants of the Physicians' Health Study and Health Professionals Follow-up Study. With linear models, we tested the association of 39 risk variants with nearby genes and all genes, and the association of each variant with canonical pathways using a global test.
  
  
  RESULTS
  In addition to confirming previously reported associations, we detected several new significant (P < 0.05) associations of variants with the expression of nearby genes including C2orf43, ITGA6, MLPH, CHMP2B, BMPR1B, and MTL5. Genome-wide, five genes (MSMB, NUDT11, RBPMS2, NEFM, and KLHL33) were significantly associated after accounting for multiple comparisons for each SNP (P < 2.5 × 10(-6)). Many more genes had an FDR <10%, including SRD5A1 and PSCA, and we observed significant associations with pathways in tumor tissue.
  
  
  CONCLUSIONS
  The risk variants were associated with several genes, including promising prostate cancer candidates and lipid metabolism pathways, suggesting mechanisms for their impact on disease. These genes should be further explored in biologic and epidemiologic studies.
  
  
  CONCLUSIONS
  Determining the biologic role of these variants can lead to improved understanding of prostate cancer etiology and identify new targets for chemoprevention.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. kpenney@hsph.harvard.edu.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Sinnott
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Tyekucheva
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Travis
authors.initials: T
authors.lastname: Gerke
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Shui
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. The Broad Institute, Cambridge, Massachusetts.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Freedman
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. The Broad Institute, Cambridge, Massachusetts. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
mesh_terms: D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors