Relation Between SNPs In IGF1 Promoter Region And Colorectal Cancer Risk In Type 2 Diabetes Patients

The incidence of colorectal cancer is higher in patients with type 2 diabetes mellitus(T2DM),but the underlying mechanisms were still poorly understood.Many studies had shown that insulin-like growth factor1(IGF1)plays an important role in the pathogenesis of T2 DM and colorectal cancer.Given that the genetic background contributes to both traits,we explored the relationship between the polymorphisms in the evolutional conserved region(ECR)of IGF1 promoter and the susceptibility of the two diseases.Objectives: 1.The association between the single nucleotide polymorphisms(SNPs)rs35767?rs5742612?rs2288377 in the IGF1 promoter region with type 2 diabetes susceptibility;2.The association between the three single nucleotide polymorphisms(SNP)of the IGF1 promoter region and the risk of colorectal cancer with or without T2 DM,and further stratified by gender,anatomical subsite.Methods:1.734 patients with T2 DM and healthy controls were included in the case-control study.Three single nucleotide polypeptides rs35767,rs5742612,rs2288377 in the ECR of IGF1 promoter region were detected.The basic information of participants were collected and glucoses(GLU)?total cholesterol(TC)?triglyceride(TG)?IGF1 were determined.Odd ratio(OR)and 95% confidence interval(CI)were calculated by Unconditional logistic regression to evaluate relation between three SNPs and susceptibility to T2 DM in native Han population.2.1468 patients with colorectal cancer and type 2 diabetes,simple colorectal cancer,T2 DM alone,and healthy controls were included in the case-control study.The clinical data of cancer patients were collected.The laboratory indicators and genotypes were detected as above.Unconditional logistic regression,adjusting the gender and age,was used to calculate the OR value and the 95% confidence interval(CI),and the relation between three SNPs and risk of colorectal cancer was evaluated in non-T2 DM and T2 DM,respectively.Further,the effects of SNPs on disease risk were evaluated in different genders and anatomical sites.Results:1.There was a significant difference in the distribution of IGF1 rs35767,rs5742612,and rs2288377 genotypes between T2 DM and healthy controls(P<0.05).For rs35767,the risk of type 2 diabetes was significantly increased in patients carrying TT genotype(OR=1.722,P=0.025),also in the dominate model(CT+TT/CC: OR=1.392,P=0.027).For rs5742612,the risk of T2 DM was significant increased in patients carrying CC genotype(OR=1.982,P=0.035,).For rs2288377,the risk of T2 DM was significant increased in patients carrying AA genotype(OR=1.982,P=0.035).The significant results were only seen in men with higher odds ratios after stratified by gender.The haplotype TTT was association with increased T2 DM susceptibility(OR=1.734,P=0.006).2.(1)Compared with the normal control group,the risk of colorectal cancer was significantly increased in patients carrying CT genotype of IGF1 rs35767(CT/CC: OR=1.377,P=0.041),also in dominant model(CT+TT/CC:OR=1.346,P=0.047).This association only occurs in the colon cancer after stratified by anatomical subsites.The haplotype TTT was association with significant increased colorectal cancer without type 2 diabetes mellitus(OR=1.599,P=0.017).(2)Among the participants with baseline diabetes,IGF1 rs35767 conferred an approximate 30% decrease in risk of colorectal cancer among dominant model(CT+TT/CC:OR=0.733,P=0.041).Compared with the CC genotype,the CT genotype had a marginal significant reduction in colorectal cancer risk(P=0.057).The association for colon alone was similar after grouping by anatomical subsites(CT+TT/CC: OR=0.623,P=0.035;CT/CC: OR=0.597,P=0.014).The haplotype TCA and TTT were association with significant decreased risk of colorectal cancer with type 2 diabetes(TCA:OR=0.698,P=0.018;TTT:OR=0.543,P=0.011).Conclusion:1.The single nucleotide polymorphism rs35767-TT ? rs5742612-CC ?rs2288377-AA and haplotype TTT in the promoter region of IGF1 were associated with increased type 2 diabetes susceptibility,which may become potential predisposing variants for T2 DM in native Han population.2.The type 2 diabetes predisposing genetic variants SNP rs35767 or haplotype TTT in the IGF1 promotor region may increase the risk of colorectal cancer without T2 DM,and decrease the risk of colorectal cancer with T2 DM,also TCA decrease the risk of colorectal cancer with T2 DM.Therefore,it is important to assess possible interactions between gene-phenotype and colorectal cancer risk.