Our meta-analysis data demonstrated, compared with those carry APOE e3 alleles, persons with APOE e4 genotype have significant decreased risk suffering from proximal CRN but not from distal CRN. Several reasons for the protective association between the allele e4 of APOE and proximal colon adenomas have been reported in past years. A proposed mechanism involving in this different effect between proximal and distal CRN is the decreased levels of fecal bile acids which may result in relative lower levels of cell proliferation in the proximal colon. A potential mechanism for this effect is the low levels of fecal bile acids which may resulting in lower levels of epithelial proliferation in the proximal colon. Serum cholesterol acids are positively related to the risk of CRN and patients with colorectal adenomas indicated high serum deoxycholic acid levels. However, in patients with the e4 allele of APOE, the levels of biliary deoxycholic acid are relatively low, which may be associated with the low incidence of adenoma and carcinoma. This has been confirmed by the results that APOE has the ability in inhibiting endothelial proliferation and APOE shows its ability in immunoregulation. It seems that the alterations in luminal cholesterol delivery and fecal bile acid are involved in the protective association of the allele e4 and proximal CRN development. APOE genotypes has been reported MRS 1191 implicated in the Methylphenidate hydrochloride breast cancer. APOE e4 allele is found to be a low-penetrant risk factor for development of breast cancer. The possible biological mechanisms of the association between APOE e4 genotype and carcinoma of the proximal colon and breast is subjects carrying APOE e4 genotype less than half of the risk of tumor cell proliferation. CRN incidences differ considerably between Western and non- Western countries. In recent years, a dramatic increase in CRC incidence has been reported in several Asian countries. Two studies from Asia included in our meta-analysis found APOE e4 was protective factor for CRN.Immigration studies have suggested that environmental factors rather than genetic susceptibility are primarily responsible for the secular trends of CRC incidence rates and international variability.