Relationship Between IGF-1 And Colorectal Cancer And Its Mendelian Randomization

Objective:IGF-1 is a single-chain polypeptide encoded by chromosome 12,mainly synthesized in the liver and regulated by growth hormone.IGF-1 appears to play a signifcant role in the development and progression of colorectal cancer.The purpose of this study is:?1?association between serum level of IGF-1,gender and age with risk of colorectal cancer in Type 2 diabetes patients.?2?Clinical assessment of combination serum IGF-1 and CEA for colorectal cancer diagnosis.?3?Relationship of SNP rs35767in IGF-1 promoter region with susceptibility to colorectal cancer.?4?Circulating insulin-like growth factors and colorectal cancer:A mendelian randomization study.Methods:1.Circulating IGF-1 levels were compared among the groups.IGF-1 cut-off value was analyzed using ROC curves.Multi-classification Logistic Regression was used to analyze the odds ratio of colorectal cancer in each subgroup.2.Collecting clinical and pathological data of patients.The diagnostic value of their detection alone and combined detection for colorectal cancer were evaluated.The diagnostic values were evaluated by receiver operating characteristic curve,AUC,sensitivity and specificity.3.In the present study,367 patients with CRC and 367 healthy subjects as the controls were enrolled.The study examined the relationship between IGF-1 rs35767polymorphism and the risk of colorectal cancer?CRC?,tumor location and degree of differentiation in a population from China.4.The association between genetic instrumental variable and the outcome supports the hypothesis that the exposure in question is causally related to the outcome.The effect values of genotype-disease will not be distorted by confounding factors.Results:1.IGF-1 levels of CRC patients with T2DM and CRC patients without T2DM were higher than that of control group?p<0.01?.In the A₁ subgroup,the odds ratio between the CRC patients without T2DM and the CRC patients with T2DM was 5.522 vs.5.893.2.For discriminating the healthy control group and CRC with D2TM group,in males?60 years old,61-70 years old,?71 years old,the sensitivity and specificity were77.94%,79.42%;78.49%,65.85%;63.64%,78.48%respectively when combination IGF-1 and CEA.3.Compared with CC genotype carriers,people with the CT genotype had a 1.39-fold higher risk of CRC?OR=1.399,95%CI=1.029¹.901 P=0.032?.Under the dominant model,TT+CT genotype frequency was signifcantly higher in the CRC group than the healthy control group?OR=1.348 95%CI=1.007¹.806 P=0.045?.4.The estimated magnitude of association for a 1.0 ng/mL change in IGF-1 level was 0.0119 for the MR analysis performed via rs35767.This translates into the risk of colorectal of 10.3%per risk allele additional of rs35767.Conclusions:1.This study demonstrates that high levels of serum IGF-1 are associated with the development of colorectal cancer.Patients with diabetes have a higher risk of having colorectal cancer than those without diabetes.The risk of developing colorectal cancer may increase significantly among male people??60 years old?with IGF-1>183.5 ng/ml.2.CEA combined with IGF-1can significantly increase the sensitivity of screening for colorectal cancer.When men were?60 years old,the diagnostic value was better than other subgroup.3.SNP rs35767 polymorphism associated with IGF-1 levels may be associated with susceptibility to colorectal cancer.People with the CT genotype may have a higher risk of CRC,and the patients who carried T allele tend to have poor tissue differentiation.4.The fact that a common genetic variant in the promoter region of IGF-1 is simultaneously associated with both serum IGF-1 levels and risk of CRC further suggests that this association is likely to be causal.