title: Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality.
abstract: BACKGROUND
  Common genetic variants in the Toll-like receptor 4 (TLR4), which is involved in inflammation and immune response pathways, may be important for prostate cancer.
  
  
  METHODS
  In a large nested case-control study of prostate cancer in the Physicians' Health Study (1982-2004), 10 single nucleotide polymorphisms (SNPs) were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kb up and downstream. Unconditional logistic regression was used to assess associations of these SNPs with total prostate cancer incidence, and with prostate cancers defined as advanced stage/lethal (T3/T4, M1/N1(T1-T4), lethal) or high Gleason grade (7 (4 + 3) or greater). Cox-proportional hazards regression was used to assess progression to metastases and death among prostate cancer cases.
  
  
  RESULTS
  The study included 1,267 controls and 1,286 incident prostate cancer cases, including 248 advanced stage/lethal and 306 high grade cases. During a median follow-up of 10.6 years, 183 men died of prostate cancer or developed distant metastases. No statistically significant associations between the TLR4 SNPs were found for total prostate cancer incidence, including SNPs for which an association was reported in other published studies. Additionally, there were no significant associations with TLR4 SNPS and the incidence of advanced stage/lethal, or high grade cancers; nor was there evidence among prostate cancer cases for associations of TLR4 SNPs with progression to prostate cancer specific mortality or bony metastases.
  
  
  CONCLUSIONS
  Results from this prospective nested case-control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. ishui@hsph.harvard.edu
authors.forename: Irene M
authors.initials: IM
authors.lastname: Shui
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Stark
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: Mara M
authors.initials: MM
authors.lastname: Epstein
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pitt
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Rulla M
authors.initials: RM
authors.lastname: Tamimi
authors.forename: Sara
authors.initials: S
authors.lastname: Lindstrom
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.forename: Katja
authors.initials: K
authors.lastname: Fall
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4