| Increasing epidemiological studies show that exogenous insulin therapy may promote colorectal carcinogenesis in type2diabetes (T2DM) patients. However, the results of the association between insulin therapy and risk of colorectal cancer (CRC) among T2DM patients are inconsistent. The growth of CRC in T2DM patients may be influenced by the insulin-insulin-like growth factor (IGF)-1signaling axis. Results from some studies suggested that higher serum IGF-1levels are associated with increased risk of CRC. Increasing studies show that the messenger RNA (mRNA) levels of local IGF-system are overexpressed in the cancer tissue of patients with CRC. However, the influence of T2DM on the expression of IGF-1and IGF-1receptor (IGF-1R) mRNA in colorectal cancer tissue and adjacent non-cancerous tissue (ANCT) is unknown.ObjectivesThe purpose of our study is to examine the effect of insulin therapy on CRC risk among patients with T2DM in an updated meta-analysis. The aim of our study is to explore the clinical characteristics of patients with T2DM and CRC. The aim of this study was to assess the mRNA expression of IGF-1and IGF-1R in paired samples of cancer tissue and ANCT between colorectal adenocarcinoma (CA) patients with and without T2DM.Contents and Methods1. Medline and Embase were searched for the reference lists of pertinent articles published from January1970to April2013. Two investigators independently extracted the data and reached consensus on the inclusion and exclusion criteria. Pool relative risks and95%confidence intervals were calculated with a random-effects model.2. To analyze the clinical characteristics, blood biochemical index, tumor markers and anti-diabetic drug usage in patients with T2DM and CRC, we retrospectively analyzed200patients with T2DM and CRC hospitalized in Tianjin Union Medicine Center during January2011to December2013.3. To quantify the levels of IGF-1and IGF-1R mRNA in CA, we analyzed the expression of IGF-1and IGF-1R mRNA levels in paired samples of cancer tissue and ANCT in CA patients with and without T2DM using real-time reverse transcription-polymerase chain reaction (RT-PCR).Results1. Analysis of six studies, including374,950participants, showed that compared with non-insulin or metformin treatment, insulin treatment was associated with an increase of37%in the risk of colorectal neoplasm among patients with T2DM, with moderate heterogeneity (I2=40%). The sensitivity analysis showed that exclusion of one small case-control study had no appreciable changes on the pooled results. Subgroup analyses suggested that there were significant positive associations between insulin therapy and risk of CRC in some subgroups, rather than all subgroups.2. The male to female ratio was1.86:1, showing that the number of male patients was higher than female. The fasting blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc) of female patients with T2DM mellitus and CRC were higher than male patients. There were significantly difference of Dukes staging between two groups (P<0.05), the proportion of Dukes B is the largest. The proportions of abnormal fasting blood GLU, carcino-embryonic antigen (CEA), LDLc in male patients were more than50%, and the proportions of abnormal fasting blood GLU, CEA in female patients were more than50%. In addition to CEA, LDLc and VLDLc, the proportions of abnormal fasting blood GLU, CA199, CA724, TC and TG in female were higher than male. Except the unknown cases of glucose-lowering drug usage, the orders of anti-diabetic drug usage from high to low were oral anti-diabetic drugs, injection anti-diabetic drug, injection+oral anti-diabetic drugs. There was no significant difference in the glucose-lowering drug usage between male and female patients (p>0.05).3. The mRNA levels of IGF-1and IGF-1R were significantly higher in cancer tissue compared with its ANCT in CA patients with and without T2DM. Compared with C A group, significantly higher levels of IGF-1and IGF-1R mRNA were observed in cancer tissue in CA with T2DM group. There was no significant difference in the role of locations. Dukes stages and diabetes duration on mRNA expression of IGF-1. Conclusions1. Our meta-analysis supports a relationship between insulin therapy and increased risk of CRC in patients with T2DM. Because of bias and confounding of included studies, caution is needed when interpreting our results. Further investigations are needed.2. Most patients with T2DM and CRC were old when they diagnosed CRC, and the majority of them were more advanced CRC cases. The usages of anti-diabetic drugs were complex, and the dose and time of medication is unknown.3. Our results support the hypothesis that IGF system plays an important role in CRC. Further larger studies are needed. |
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