| Backgroud:Colorectal cancer (CRC) is one of the most common malignant tumors. The morbidity and mortality of CRC are gradually increasing in recent years in China. Early diagnosis and treatment will improve its prognosis. Many developed western countries, including US, has specific CRC screening guideline. And with the implementation of the guideline, CRC incidence has been declining.Due to many factors, no screening guideline is available in China so far. With the enhancing awareness on health and cancer prevention in general population, many people choose annual health examination, but whether colonoscopy should be taken towards the health examination population remains unclear. Domestic study has shown high risk factors of colorectal cancer include positive CRC famlily history, history of polyps, chronic constipation, diarrhea, appendectomy, cholecysyectomy and fecal occult bleeding test (FOBT) positive. But whether the factors increase CRC susceptibility remain to be proved. In China, the number of rectal cancer is higher than that of colon cancer,which is different with the data of western countries. Distinct epidemiological and clinicopathological evidence indicated different risk factors and pathways of transformation associated with colon and rectal carcinogenesis. Etiology and the oncogenetic mechanisms of these two cancers should be studied separately. Our previous study by gene expression microarray showed much difference exists between colon and rectal cancer in terms of gene expression profile and signal transduction pathways. Several genes will be proved to clarify the different carcinogenesis between colon and rectal cancer. And the results will offer important references in CRC diagnosis and treatment in the future.Objectives:Our study of the part one aims to identify CRC high-risk people among health examination population by a questionnaire and then to analyse their colonoscopy results and finally to explore the feasibility by using questionnarire containg high risk item of CRC in combination with colonoscopy to screen CRC and precancerous lesions in order to provide reference to the CRC screening guideline in the future.The objective of our second study based on the previous study of gene expression microarray is to explore the biomarker distinguishing colon and rectal cancer.Methods:From May2010to June2011, we screened, by a questionnaire containing high-risk items, the population at high risk of CRC among the adults who underwent health examination in Peking Union Medical College Hospital(PUMCH) health examination center. The high-risk people were asked to undergo colonoscopy, and the detection rate of colorectal polyps as well as its clinical features were analysed. The performance value and its respective acceptibility of each risk item were explored. Our previous study investigated the differences of gene expression profiles and carcinogenesis pathways between12righted-sided colon and12rectal cancers by gene expression microarray. In reference to the prior results of the gene expression profile and after consulting relevant documents with cancer, six genes(TFF1, REG1A, S100P, ASCL2,OLFM4and XPNPEP3) were discreetly selected.All of six genes were verified by reverse transcription PCR (RT-PCR) in30human right-sided colon and30rectal cancer tissues and the same number of adjacent non-cancerous tissues were used as normal control group with samples matched in clinical features. The statistically significant genes by RT-PCR were further proved by Q-PCR in15patients with righted-colon cancer and15patients with rectal cancer.. Genes that were statistically highly expressed in colon or rectal cancer were further verified by immunohistochemistry in tissue slices of15patients with righted-sided colon cancer and15patients with rectal cancer.Results:Among a total of5470adults,456(8.3%) were at high risk of CRC.236(51.8%) underwent colonoscopy, but only225subjects including lllmen(49.3%),114women(50.7%) received complete colonoscopy.Mean age:50.3±11.2years64(28.4%) had colorectal polyps and16(7.1%) had advanced polyps.There was no significant difference in the detection rate of polyps and advanced polyps between men and women (p>0.05). People older than50years had higher rates of colorectal polyps and advanced polyps (p<0.01). Mucous and bloody stool had the highest positive predict value, highest negative predict value, Youden index and the lowest negative likelihood ratio in screening for polyps. A history of chronic constipation had the highest sensitivity and the highest likelihood ratio. FOBT positive, mucous and bloody stool, chronic diarrhea and history of polyps had significant higher colonoscopy compliance (p=0.004,0.000,0.009,0.004, OR=9.5,3.2,3.1,2.0), but no significant difference were found in gender and ages (p>0.05).RT-PCR results showed that all of the six genes were statistically significant in cancers(p<0.05) compared with adjacent normal tissues. But TFF1, REG1A and S100P were also significantly highly expressed in right-sided colon cancer in comparison with that in rectal cancer (p<0.05); Compared with right-sided colon cancer, ASCL2was significantly highly expressed in rectal cancer (p<0.05). OLFM4and XPNPEP3didn’t show significant difference between colon and rectal cancers(p>0.05). The results of Q-PCR were in a substantial agreement with that of RT-PCR. Finally, TFF1and ASCL2 were proved by immunohistochemistry. The results showd TFF1and ASCL2were statistically highly expressed in colon cancer and rectal cancer respectively (p<0.05).Conclusion:Colonoscopy results showed the population at high risk of CRC identified by the questionnaire did has a high detection rate of colorectal polyps. Mucous and bloody stool had the highest positive predict value, highest negative predict value, Youden index and the lowest negative likelihood ratio in screening for polyps. A history of chronic constipation had the highest sensitivity and the highest likelihood ratioA history of chronic constipation had the highest sensitivity. FOBT positive,mucous and bloody stool,chronic diarrhea and history of polyps had significant higher colonoscopy compliance. It is important and valuable for Chinese CRC high-risk population especially older than50years to undergo colonoscopy in health examination place. We will perfect our questionnaire, hoping to extend its application in more regions in China. Our study will provide important references for clinical doctors and shed lights on the planning of CRC screening before the debut of national screening guideline.Basically, the proof results coincided with that of the previous gene microarray and it paved the way for our accurate selection among numerous genes. Our ultimate results found TFF1highly expressed in colon cancer and ASCL2in rectal cancer. Both of them rendered potential candidates for distinguishing between colon and rectal cancer and provide the theoretical foundation for targeted therapy of colorectal cancer in the future. |
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