Toll-like receptor 4 genetic variation and advanced prostate cancer risk.
Toll-like receptor 4 (TLR4) is a key innate immunity receptor that initiates an inflammatory response primarily against Gram-negative bacteria. Two recent publications reported that variants in TLR4 were associated with risk of prostate cancer. To further investigate the role of TLR4 in prostate cancer susceptibility, we identified six tagging single-nucleotide polymorphisms that comprehensively captured the common genetic variation of the locus and tested these polymorphisms in our case-control study of 1,012 men. Two single-nucleotide polymorphisms showed nominally statistically significant associations with prostate cancer risk, with the strongest (rs10759932) associated with a 4-fold increased risk of disease (P = 0.006). We estimated through permutation analysis that a similarly strong result would occur by chance 2.5% of the time. Our findings support previous studies and suggest that inherited differences in TLR4 influence prostate cancer risk.
Cheng
Iona
I
Department of Epidemiology and Biostatistics and Center of Human Genetics, University of California at San Francisco, 94143-0794, USA.
Plummer
Sarah J
SJ
Casey
Graham
G
Witte
John S
JS
D000368:Aged; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4