The role of genetic variation in Toll-like receptor 4 in prostate cancer susceptibility: a review

Abstract

Toll-like receptor 4 (TLR4) is a key innate immunity receptor that initiates an inflammatory response against invading pathogens. Recent association studies have identified genetic variants in TLR4 that appear to influence the risk of prostate cancer. To evaluate critically whether genetic variation in TLR4 influences prostate cancer susceptibility, a systematic review of the literature on TLR4 and prostate cancer is done. All genetic association studies of TLR4 and prostate cancer are evaluated. In particular, issues related to genetic coverage, study heterogeneity and multiple hypothesis testing are examined. Although all three of the published studies suggest that the TLR4 locus itself is associated with prostate cancer, there is no corroboratory evidence for which specific variants influence the risk of disease. Clearly, these studies alone cannot establish TLR4 as a prostate cancer susceptibility locus. By evaluating candidate genes such as TLR4 further in conjunction with other variants identified by genome-wide association studies of prostate cancer, we shall be better poised to develop the appropriate panel of markers to improve prevention and diagnosis.