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Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.

About this Publication
Title
Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.
Pubmed ID
25360682 (View this publication on the PubMed website)
Publication
PLoS ONE. 2014; Volume 9 (Issue 10): Pages e110569
Authors
Weng PH, Huang YL, Page JH, Chen JH, Xu J, Koutros S, Berndt S, Chanock S, Yeager M, Witte JS, Eeles RA, Easton DF, Neal DE, Donovan J, Hamdy FC, Muir KR, Giles G, Severi G, Smith JR, Balistreri CR, ...show more Shui IM, Chen YC
Affiliations
  • Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
  • Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, United States of America.
  • Channing Laboratory, Department of Epidemiology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
  • 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.
  • Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
  • 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.
  • Department of Epidemiology and Biostatistics and Center of Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
  • The Institute of Cancer Research, Sutton, United Kingdom.
  • Centre for Cancer Epidemiology, Departments of Public Health and Primary Care and Oncology, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom.
...show more
  • Surgical Oncology (Uro-Oncology: S4), Departments of Oncology and Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
  • Department of Social Medicine, University of Bristol, Bristol, United Kingdom.
  • Academic Urology Unit, University of Sheffield, Sheffield, United Kingdom.
  • University of Nottingham Medical School, Queens Medical Centre, Nottingham, United Kingdom.
  • Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
  • Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
  • Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Palermo, Italy.
  • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
  • 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.
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.

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