title: Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews.
  
  
  METHODS
  We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls.
  
  
  RESULTS
  Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity.
  
  
  CONCLUSIONS
  TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.
authors.affiliation: Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Weng
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Channing Laboratory, Department of Epidemiology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: John H
authors.initials: JH
authors.lastname: Page
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jen-Hau
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Stella
authors.initials: S
authors.lastname: Koutros
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Sonja
authors.initials: S
authors.lastname: Berndt
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.affiliation: Core Genotyping Facility, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, United States of America; Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, United States of America.
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.affiliation: Department of Epidemiology and Biostatistics and Center of Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
authors.affiliation: The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.affiliation: Centre for Cancer Epidemiology, Departments of Public Health and Primary Care and Oncology, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.affiliation: Surgical Oncology (Uro-Oncology: S4), Departments of Oncology and Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: Department of Social Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: Donovan
authors.affiliation: Academic Urology Unit, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: University of Nottingham Medical School, Queens Medical Centre, Nottingham, United Kingdom.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Muir
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
authors.forename: Graham
authors.initials: G
authors.lastname: Giles
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Smith
authors.affiliation: Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Palermo, Italy.
authors.forename: Carmela R
authors.initials: CR
authors.lastname: Balistreri
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Shui
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Research Center for Genes, Environment and Human Health, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Chen
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4