It was speculated APOE e4, which is associated with more intracellular release of free than that of e3 and lower concentrations of fecal bile acids in the gastrointestinal tract, has its protective role against CRC. The APOE e4 allele appears to be associated with an increased risk of gallstones and breast cancer. Our present data indicated that the APOE gene polymorphisms were similar between patients with CRN and controls. Our data also demonstrated APOE e4 did not Spiperone hydrochloride affect the overall risk for CRA, there was not a protective effect in patients with e4 when compared to those with e3. Despite the genetic factors has been suggested to be important for the susceptibility to CRN, other factor like racial differences may also play a role. First, genetic heterogeneity may be a reason for the conflicting results. In people of European ancestry, APOE genotype showed a positive doseresponse association with LDL-C while study of Brazilian individuals indicated that the presence of the e4 genotype may be a protective effect against CRC. In addition, the allele e4 is much less frequent in Japanese than in Caucasians, and it was reported Finns seem to have a particularly high frequency of the allele e4. In our meta-analysis, the included 8 studies are from Japan, Brazil, China, Australia, Finland, USA, UK, and Canada respectively on evaluating the APOE polymorphisms in relation to CRN. In addition, our data indicated the contribution of APOE polymorphisms to CRN susceptibility varies in different studies. For ethnic diversity, distinct environmental factors and eating habits characterize populations, analyze the allelic and genotypic distributions of the APOE and their association with CRA or CAC should characterize the histories and habits of people. We also evaluated association of genetic variants of APOE with proximal and distal CRN. Three of the 8 included studies 8-Hydroxy-2-deoxyguanosine involving evaluated the presence of APOE polymorphisms to different parts of the colorectal tumors. Although APOE e4 did not affect the overall risk for CRN, there was a trend towards a protective effect in patients with right-sided cancer when compared to those with left-sided carcinoma. However, the degree of this protection was less prominent reported by Kervinen et al. from Finland.