Study On Epidemiology Of Colorectal Cancer In Wuhan

Study BackgroundColorectal cancer (including colonic and rectal cancer) is one of the most common cancers that threatening the public health heavily. In the developed world, CRC represents a major public health problem. In the UK and the USA, CRC is the second most common cancer after breast cancer for women, and after prostate or lung cancer for men. The incidence in North America, Western Europe approximates or exceeds 40 cases per 100000 of the population in males and 25-30 cases per 100000 in females. In Asia, so as in China, the incidence is relatively low, but it shows an increase trend.From 20 century 70th, five cities (Beijing,Tianjing,Shanghai,Wuhan, Ha erbing) and six rural areas (Ci county in Hebei Province, Linzhou county in Henan Province, Jianshan county in Zhejiang Province, Changle county in Fujian Province, Fusui county in Guangxi Province) in China have established tumor register system gradually to collect the information about incidence and mortality of malignant tumor including colorectal neoplasm. From 1993 to 1997, the incidence rate and mortality rate of colorectal cancer ranked 3 to 5 among all of the cancers in China. In the five cities, the incidence rate of colorectal cancer is relatively high in Shanghai and Beijing. In Shanghai, the incidence rate and mortality rate is 32.1 cases per 100000 and 17.9 cases per 100000 for female, ranking first; The mortality rate ranked second for female in Beijing and ranked 3th to 5th in other three cities. In rural areas, the incidence rate of colorectal cancer is highest in Jianshan county, where is 22.8 casesper 100000 for female, ranking first in incidence spectrum. Qidong County in Jiangsu Province and Lizhou County in Henan Province is the lower, while Fusui county in Guangxi Province is the lowest, ranked tenth in incidence spectrum. The highest incidence and mortality rate for male is in Jiashan county, Zhejiang Province, where is 25.6 cases per 100000 and 20.6 cases per 100000 respectively. From 1990 to 1992, the mortality rate of colorectal cancer increased 31.95 percent in large city, and 8.51 percent in rural area. In Shanghai, the incidence rate of colorectal cancer increased at a speed by 4.2 percent every year. Therefore, it is expected that the incidence and mortality rate of colorectal cancer will increase in the future. Then, colorectal cancer will become one of the most important malignant tumors.As well as other malignant tumors, great efforts have been conducted by researchers in the field of basic theory and clinical study of colorectal cancer, and many achievements have been gained. But the study of etiology of colorectal cancer is in progress, and has not certain conclusion. The pathogenesis of colorectal cancer need to be explored more.In this study, the data about mortality rate of colorectal cancer in Wuhan city will be analyzed to predict the prevalence trend (mortality rate) of colorectal cancer in Wuhan; The recent risk factors of colorectal cancer in Wuhan will be investigated; At last, pathogenesis of colorectal cancer will be explored by Meta analysis and immunohisochemistry, to provide basis for the prevention of colorectal cancer.Objectives of Study1. To predict the prevalence trend (mortality rate) of colorectal cancer in Wuhan, and explore the reliability of the Grey Model;2. To investigate the recent risk factors of colorectal cancer in Wuhan, and provide correspondingly preventive measures and screening methods for colorectal cancer;3. To evaluate the relationship between circulating levels of IGF-1, IGFBP-3 and IGF-2 and colorectal cancer by Mata analysis, to prove the new hypothesis of colorectal cancer—environmental factors influence the risk of colorectal cancer by IGF system;4. To study the relationship between IGF-2 expression and the biological behavior, the expression of survivin, c-myc in colorectal cancer cases;5. To study the relationship between survivin expression and the biological behavior, the expression of bcl-2 and ki index in colorectal cancer cases.Subject (Material) and Method 1. Subject1.1 Research on the Prediction of the Prevalence of Colorectal Cancer:To collect the mortality data through death register system in Wuhan Disease Control Center. The total number of Wuhan population in 1994-2002 was calculated basing on the data of Wuhan population from the forth China population census and the variation data of Wuhan population.1.2 Research on recent Risk Factors of Colorectal Cancer in Wuhan, China: Sample size was estimated according to α =0.05 and power of test (1-β)=0.9 before we conducted a unpaired case-control study for this program. From 1st March 2003 to 30th September 2004, 164 patients diagnosed by pathology were selected from three comprehensive hospitals and one tumor-specialized hospital in Wuhan including 100 male and 64 female patients.1.3 Meta-analysis on serum IGF-1 , IGFBP-3, IGF-2 and colorectal cancer: eight epidemiological studies on insulin-like growth factors and risk of colorectal cancer were selected by Internet.1.4 Expression of IGF-2 gene in colorectal cancer and its significance:Samples were selected from the subject of 1.2 and cases in Hubei tumour hospital in 20051.5 Expression of survivin gene in colorectal cancer and its significance: The selection of sample is the same as 1.42.Methods2.1 Research on the Prediction of the Prevalence of Colorectal Cancer:the prediction model was established based on the Grey Model, predicting the resultdynamically using "Same Dimension-Progressively Increased Grey DynamicPrediction", modifying the prediction results by considering the "EnvironmentInterference Factors".2.2 Research on recent Risk Factors of Colorectal Cancer in Wuhan, China:With case-control study, after investigating candidate colorectal cancer risk factorinformation and general information of 164 cases and 328 control people,single-factor logistic regression analysis was firstly used to calculate OR value and95% C.I. of significant factors. Then multi-factor logistic regression analysis was usedon the basis of single-factor analysis.23 Meta-analysis on serum IGF-1, IGFBP-3, IGF-2 and colorectal cancer:We performed a meta-analysis of 8 epidemiological studies on insulin-like growthfactors and risk of colorectal cancer2.4 Expression of IGF-2 gene in colorectal cancer and its significance:The expression of IGF-2, survivin, c-myc and ki index was detected in 44 cases of the primary colorectal cancer, 20 cases of the normal tissue by using immunohistochemical SP.2.5 Expression of survivin gene in colorectal cancer and its significance:The expression of survivin, bcl-2 and ki index was detected in 44 cases of the primary colorectal cancer, 20 cases of the normal tissue by using immunohistochemical SP.Results1. Research on the Prediction of the Prevalence of Colorectal Cancer: The mid-time and long-term predictions about mortality rate of colorectal cancer were made based on the GM(1,1) model. The predicting value of mortality rate in 2003～ 2011 for males is(unit:l per 100000): 10.156, 10.872, 11.450, 11.998, 12.692, 13.341, 14.031, 14.737, 15.568; For females is: 8.969, 9.275, 9.454, 9.867, 9.999, 10.290, 10.584, 10.961, 11.223; For whole population is: 9.576, 10.089, 10.468, 10.943, 11.354, 11.816, 12.298, 12.826, 13.360. The measurements about how to prevent colorectal cancer were summarized according to the results of thisresearch.2. Research on recent Risk Factors of Colorectal Cancer in Wuhan, China:That the history of chronic appendicitis, first degree relatives who suffered fromcancer, the poor ability of adjusting the mood, passive smoking, and the frequency ofsalted foods ten years ago were closely associated with colorectal cancer. Thecorresponding adjusted Odds Ratio (ORs) were 7.411(95%CI: 2.413-22.760),3.059(95%CI: 1.718-5.450), 1.782(95%CI: 1.328-2.389), 1.325(95%CI: 1.147-1.530)and 1.221(95%CI: 1.114-1.340) respectively. There was a protective effect providedby the habit of eating cool foods, eating soft foods, low-salted foods for colorectalcancer, the corresponding adjusted ORs were 0.465(95%CI: 0.333-0.647),0.606(95%CI: 0.470-0.781) and 0.615(95%CI: 0.480-0.790) respectively.3.A meta-analysis on serum IGF-1, IGFBP-3, IGF-2 and colorectal cancer:The pooled odds ratio(OR) of IGF-1 and IGFBP-3 were 1.59 and 0.76 respectively.According to the different measurements(ELISA and IRMA) , the pooled OR was1.92 and 1.31 for IGF-1, 0.46 and 1.34 for IGFBP-3 respectively. The pooled OR ofIGF-2 was 2.16.4.Expression of IGF-2 gene in colorectal cancer and its significance:1) The positive rates of survivin expression were 27.3% in cancer tissue and 5.0% inmarge tissue respectively. The difference between them was significant. Significantrelationships were found between IGF-2 expressions and Duke's stage, lymphmetastasis of colorectal cancer (P<0.05).2)The c-myc, survivin expression was not associated with the IGF-2 expression(P>0.05).5. Expression of survivin gene in colorectal cancer and its significance:1) The positive rates of survivin expression were 63.6% in cancer tissue and 0% in tumor marge tissue respectively. The difference between them was significant. Significant relationships were found between survivin expressions and sex of colorectal cancer cases(P<0.05).2) The bcl-2 expression was not associated with the survivin expression (P>0.05).3) The mean Ki in survivin positive tumors was significant higher than that insurvivin negative tumors(P<0.01).Conclusions1. In the recent future, the mortality rate of colorectal cancer in Wuhan, especially formale, showed a significant increase trend.This situation is similar with other cities. From the results of model based on1994-2000 data, we can see that the real male mortality rate in 2001 is close to theupper limit of prediction interval, and is beyond the upper limit of prediction intervalin 2002. It shows that there are environmental factors leading to increase the malemortality rate.2.This research provided new and important means for prediction of colorectal cancer.The short-term prediction results have been confirmed and the long-term predictionneed to be further studied.3. The recent risk factors of colorectal cancer is different from old studiesThe above findings indicate that the risk of colorectal cancer is significantly associated with the history of chronic appendicitis, family history of cancers, psychological factors, and dietary factors.4. IGF-1 and IGF-2 are associated with colorectal cancerHigh serum levels of IGF-1 and IGF-2 were the independent risk factors of colorectal cancer, and the OR of IGFBP-3 was not statistically significant. The heterogeneity between studies on IGFBP-3 and colorectal cancer was due to the different measurement, but there is still a need to conduct large size study using 2 different measurements simultaneously to further prove it.5. IGF-2 is a prognostic factor, and it is included in the pathogenesis of colorectal cancer. IGF-2 expression is associated with malignant degree of colorectal cancer, and detection of it has positive effects on prognosis evaluation.6. Survivin is included in the pathogenesis of colorectal cancerSurvivin expression is associated with sex of colorectal cancer cases. Survivin plays certain roles in the oncogenesis and progression of colorectal cancer.Suggestion to the prevention of colorectal cancer1.We should put emphasis on the prevention and control work of colorectal cancer atpresent and in recent future. 2.The government should be involved in the work of colorectal cancer control andprevention.3.Strengthen the surveillance of colorectal cancer4.Undertake the health education in community, advocate the healthy life-style 5.Implement high-risk group strategy 6.Reinforce the study of pathogenesis of colorectal cancerCreative Points of the study1. Firstly use "Same Dimension-Progressively Increased Grey Dynamic Prediction" topredict the prevalence trend of colorectal cancerAt present, the methods which are usually used to predict prevalence and mortalitytrend of malignant tumor are trend extrapolation, Box-Jenkins model, mixed model.The "Same Dimension-Progressively Increased Grey Dynamic Prediction" has notbeen seen in the field of malignant tumor prediction.2.Study the recent risk factors of colorectal cancer in Wuhan thoroughlyThis study investigated the risk factor from both environmental and hereditaryaspects.3. Evaluate the relationship between circulating levels of IGF-1, IGF-2, IGFBP-3 andcolorectal cancer by meta-analysis firstlyWe performed a meta-analysis of 8 epidemiological studies on insulin-like growthfactors and risk of colorectal cancer. The results showed that high serum levels ofIGF-1 and IGF-2 were the independent risk factors of colorectal cancer, and the ORof IGFBP-3 was not statistically significant. This is the first meta-analysis study about1GF-1, IGF-2, IGFBP-3 and colorectal cancer.4.Study the relationship between IGF-2 and Survivin expression firstlySurvivin is the new member of Inhibition Apoptosis Protein, while IGF-2 is a riskfactor for colorectal cancer recently mentioned. There are some report about thecolorectal cancer and these two genes individually, but the jointed expression of them is lacked.