【正文】 c Health College of Harbin Medical University ras 癌基因家族 根據(jù)不同時期，不同組織的癌基因表達(dá)，將 ras基因家族分為三類： Hras 胃癌 膀胱癌 宮頸癌 Nras 白血病 肝癌 Kras 胰腺癌 肺癌結(jié) 腸癌 (Family members of ras) Department of Epidemiology Public Health College of Harbin Medical University 致癌病毒 (Cancerinducing virus) 病 毒 核酸結(jié)構(gòu) 癌基因 乳多空病毒 環(huán)狀雙鏈 DNA T抗原基因 腺病毒 線狀雙鏈 DNA E1A， E1B 皰疹病毒 線狀雙鏈 DNA EB序列 反轉(zhuǎn)錄病毒 單鏈 RNA ras,src等 Department of Epidemiology Public Health College of Harbin Medical University 腫瘤抑制基因（ tumor suppressor gene） 一類與細(xì)胞周期調(diào)控有關(guān)的基因，當(dāng)這些基因正常表達(dá)時，具有抑制細(xì)胞分裂的功能。 1968年 Harris實(shí)驗(yàn)： 癌細(xì)胞系 X 正常細(xì)胞 無惡性表型細(xì)胞 正常 癌細(xì)胞 （染色體部分丟失） Department of Epidemiology Public Health College of Harbin Medical University 首先發(fā)現(xiàn)的腫瘤抑制基因 (First discovered Tumor Suppressor Gene) 視網(wǎng)膜母細(xì)胞瘤 發(fā)現(xiàn) Rb基因缺失呈雜合體時，細(xì)胞是正常的，缺失純合體時細(xì)胞轉(zhuǎn)化。 Rb純合缺失后致癌表明 Rb基因存在時對腫瘤細(xì)胞有抑制作用，因此 Rb是腫瘤抑制基因。 Department of Epidemiology Public Health College of Harbin Medical University ① 闡明影響惡性腫瘤發(fā)病率或死亡率的地區(qū)間差別和時間趨勢的因素； ②研究不同社區(qū)人群間惡性腫瘤發(fā)病率與人們生活方式和環(huán)境間的相互關(guān)系； ③比較患惡性腫瘤和不患惡性腫瘤人群之間可疑危險因素的暴露情況，比較暴露和未暴露于可疑危險因素人群惡性腫瘤發(fā)病情況； 惡性腫瘤流行病學(xué)的主要研究領(lǐng)域 Department of Epidemiology Public Health College of Harbin Medical University ④ 對惡性腫瘤危險因素實(shí)施干預(yù)并評價干預(yù)效果； ⑤對惡性腫瘤發(fā)病機(jī)制和模型進(jìn)行定性和定量研究，闡明其發(fā)病機(jī)理 Department of Epidemiology Public Health College of Harbin Medical University 描述流行病學(xué)研究 (Descriptive epidemiologic study) To describe the difference in occurrence of a particular cancer between different groups (age, gender, race, country, a period of time for time trend) and to generate the hypothesis for increased/decreased for the specific tumor type. Department of Epidemiology Public Health College of Harbin Medical University 建立健全的健康信息系統(tǒng)（ health information system， HIS） 是完整描述惡性腫瘤分布和流行趨勢的最科學(xué)、有效的途徑。國際癌癥研究中心的匯報 《 五大洲癌癥發(fā)病率 》 收錄了腫瘤登記工作開展較早的地區(qū)的腫瘤發(fā)病信息，目前已出版第七卷。此次征求意見的專家，基本涵蓋了目前世界衛(wèi)生組織、美國、芬蘭、英國以及國內(nèi)從事慢病監(jiān)測、流行病與衛(wèi)生統(tǒng)計學(xué)、疾病控制、人口學(xué)等相關(guān)領(lǐng)域的近四十位權(quán)威學(xué)者。其余專家的意見正陸續(xù)反饋到慢病中心。 Department of Epidemiology Public Health College of Harbin Medical University 專項(xiàng)的惡性腫瘤流行病學(xué)橫斷面研究，如江蘇啟東、海門地區(qū)的肝癌、揚(yáng)中地區(qū)的胃癌和食管癌研究等，反映了這些消化系統(tǒng)癌癥在高發(fā)地區(qū)內(nèi)不同時間、空間和人群間的分布，為建立和檢驗(yàn)消化系統(tǒng)癌癥危險因素假設(shè)提供了可靠的背景材料。 Department of Epidemiology Public Health College of Harbin Medical University ? 病例對照研究是腫瘤病因?qū)W研究的常用方法。 ? 隊(duì)列研究包括前瞻性和回顧性隊(duì)列研究。 分析流行病學(xué)研究 (Analytic epidemiological study) Department of Epidemiology Public Health College of Harbin Medical University ? 山西子宮頸癌篩查研究隊(duì)列數(shù)據(jù)庫 中國醫(yī)學(xué)科學(xué)院腫瘤研究所與美國克里夫蘭醫(yī)學(xué)中心、美國 NCI合作進(jìn)行。試驗(yàn)結(jié)果在法國獲 “ 歐羅金 ”國際獎。對子宮頸癌篩查手段進(jìn)行了科學(xué)的評價，同時在病因流行病學(xué)研究亦有重要意義。 Department of Epidemiology Public Health College of Harbin Medical University 不但有助于干預(yù)或預(yù)防腫瘤的發(fā)生，而且能為腫瘤病因?qū)W研究提供有關(guān)危險因素或病因的進(jìn)一步佐證。營養(yǎng)干預(yù)試驗(yàn)共干預(yù)人群共 32902例，至今一直對干預(yù)人群進(jìn)行跟蹤隨訪及定期普查；食管癌早診早治及化學(xué)預(yù)防研究于 1998年啟動，研究人群 2213例，經(jīng)內(nèi)窺鏡檢查確定食管上皮病變，對其中輕、中度不典型增生病人進(jìn)行化學(xué)藥物預(yù)防研究。 (Biomarker and tumor epidemiological study) Department of Epidemiology Public Health College of Harbin Medical University ⑴ 內(nèi)劑量（ In doses ） ⑵生物學(xué)效應(yīng)劑量（ Biological effective dose） ⑶臨床前期生物學(xué)效果（ Preclinical biological effects ） ⑷易感性標(biāo)志（ Susceptibility marker ） 生物標(biāo)志流行病學(xué)研究的方法學(xué)問題 生物標(biāo)志種類 (Types of Biomarker) Department of Epidemiology Public Health College of Harbin Medical University Molecular Epidemiology Breaking Open the “Black Box” Department of Epidemiology Public Health College of Harbin Medical University Molecular Epidemiology Internal Dose (Agent Metabolite) Biological Effective Dose (Adducts) Preclinical Biologic Effect (SCE oncogene TSG inactivation) Exposure Disease Department of Epidemiology Public Health College of Harbin Medical University 第二節(jié) 惡性腫瘤的流行特征 (惡性腫瘤的疾病負(fù)擔(dān) ) Epidemiological Characteristics of Malignancy Department of Epidemiology Public Health College of Harbin Medical University Measures of Cancer Frequency: Incidence ? number of new cases occurring ? can be expressed as an absolute number of cases per year or as a rate per 100,000 persons per year. ? incidence rate provides approximation to average risk of developing a cancer and is necessary to pare risk of disease between populations ? reduction in incidence is the appropriate statistics to use when considering impact of primary prevention strategies Department of Epidemiology Public Health College of Harbin Medical University Measures of Cancer Frequency: Mortality ? number of deaths occurring ? mortality rate is the number of deaths per 100,000 persons per year ? mortality rates measure average risk of dying from a specific cancer ? number of deaths is one measure of oute or impact of cancer (product of incidence and fatality of a given cancer) ? Fatality, (1survival), is probability that an individual with cancer will die from it a