| Objectives:①To explore the risk factors and protective factors of susceptibility of CRC(Colorectal Cancer) in Wuhan City,②To explore the association between the A-202C(rs2854746) and G2133C(rs2854744) polymorphism in IGFBP-3 (Insulin like growth factorbinding protein-3) gene and CRC.③To explore the association between haplotype ofIGFBP-3 gene and CRC.④To explore and assess the possible interaction effects betweenIGFBP-3 gene polymorphisms and environmental factors.Methods: A hospital based case-control study was performed in this study. A total of 202cases were those onset CRC patients registered in one specific hospital in Wuhan. Thecontrols were selected from patients without tumors and digestive diseases. The cases andcontrols were interviewed with the same questionnaire, and the blood samples were drawn interms of the same conditions and standards. Gene polymorphisms were determined by usingTaqman MGB genotyping assay. Univariate and multiple logistic regression models wereused to explore the association between the genes polymorphisms and CRC. Haplotypeanalyses of these polymorphisms were performed using PHASE2.0 software. Additionally, theinteraction between genes and environmental risk factors was assessed by multivariatelogistic regression model. The odds ratio values (OR) was calculated by using regressionmodel to determine the addition effects among different factors and measure the interaction..Results:①After adjustment for gendar, age, smoking status, alcohol consumption and BMI index, univariate logistic regression demonstrated that some environmental exposure factorswere correlated with the susceptibility of CRC. Among these factors, some were independentrisk factors including direct relative history, high intake of red meat, firing, fried andsmudging foods. The corresponding OR is 2.571 (95%CI=1.421-4.127), 2.051(95%CI=1.123-3.417), 1.754 (95%CI=1.035-3.451), 1.713 (95%CI=1.005-2.841) and 3.294(95%CI=1.105-8.946) respectively. However, moderate physical work and high intake offresh vegetables were protective factors, the corresponding OR is 0.374 (95%CI=0.145-0.745)and 0.652 (95%CI=0.425-0.986)respectively.②After adjustment for gendar, age, smoking,drinking and BMI index , for IGFBP-3 A-202C polymorphism, there was no significantdifference in the distributions of genotypes between two groups. For IGFBP-3 G2133Cpolymorphism, unconditional logistic regression analyses revealed that participants carryingthe G2133C GC heterozygote or CC homozygote had a significantly 1.55-fold (adjusted OR =1.56, 95% CI=1.05-2.29) increased risk of CRC.③There were seven haplotypes for theabove two polymorphisms. Compared with GA/GA haplotype, GA/CA genotype wassignificant associated with an increased risk of developing CRC without adjusting for otherconfounding factors (OR=1.99, 95%CI=1.15-3.41).④The positive additive interactions werefound between IGFBP-3 gene A-202C polymorphism and direct relative history, SynergyIndex (S) was 1.23. Similarly, a positive additive interaction was found between G2133C andhigh intake of red meat (S=1.55), and the S for high intake of fried food was 1.46.Conclusions:①The classical risk factors are still main reasons of patients with CRC ofWuhan city. Therefore it is an important measure to prevent CRC in community population topropose healthy life style and porstulate good eating habit.②The study showed that thegenotype distribution of G2133C (rs2864746), but not A-202C (rs2864744), was significantlydifferent between cases and controls.③The study showed some haplotypes were significantassociated with an increased risk of developing CRC.④There are obvious interactionsbetween A-202C and G2133C polymorphisms in IGFBP-3 gene and environmental factors such as family history tumor diseases, high take of red meat and fried foods.⑤CRC iscaused by the interactions between many minor genes and environmental risk factors. It isvery important to study their correlation to classify the cause and pathogenesis of CRC.
|
PDF Full Text Request