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

• Published in: PloS one 2014-10, Vol.9 (10), p.e110569-e110569
• Main Authors: Weng, Pei-Hsuan, Huang, Yi-Ling, Page, John H, Chen, Jen-Hau, Xu, Jianfeng, Koutros, Stella, Berndt, Sonja, Chanock, Stephen, Yeager, Meredith, Witte, John S, Eeles, Rosalind A, Easton, Douglas F, Neal, David E, Donovan, Jenny, Hamdy, Freddie C, Muir, Kenneth R, Giles, Graham, Severi, Gianluca, Smith, Jeffrey R, Balistreri, Carmela R, Shui, Irene M, Chen, Yen-Ching
• Format: Article
• Language: English
• Subjects: Age; Biology and Life Sciences; Cancer; Cancer genetics; Cardiovascular disease; Disease prevention; Epidemiology; Genes; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Genotypes; Hazards; Health aspects; Health care; Health risks; Heredity; Hospitals; Humans; Immune system; Immunity, Innate - genetics; Inflammation; Laboratories; Leukocytes; Male; Medical ethics; Medical research; Meta-analysis; Nutrition research; Oncology; Pathogenesis; Physical Sciences; Polymorphism, Single Nucleotide; Preventive medicine; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Proteins; Public health; Regression analysis; Research and Analysis Methods; Reviews; Risk; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Systematic review; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-like receptors; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0110569

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. 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. 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. TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.