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DEVELOPMENT OF BIOLOGICAL MARKERS FOR INDIVIDUAL CANCER RISK AND CANCER PREVENTION ON THE BASIS OF A PROSPECTIVE COHORT STUDY

基于前瞻性队列研究开发个体癌症风险和癌症预防的生物标志物

基本信息

批准号：
11138263
负责人：
NAKACHI Kei
金额：
$ 6.4万
依托单位：
Research Institute for Clinical Oncology, Saitama Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas (A)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11138263/
关键词：
Prospective cohort study NK activity Immunosurveillance

项目摘要

We investigated host-environmental interaction involved in human carcinogenesis in terms of a prospective cohort study among a general population (a total of 3,625 individuals aged over 40 years), using various biological markers along with a questionnaire on lifestyle. An eleven-year follow-up survey on cohort members found a total of 192 cancer cases, revealing that NK (natural killer) activity of peripheral blood lymphocytes (PBL), which was assessed at baseline by isotope-release assay using K562 as target cells, showed a negative association with cancer incidence. Categorizing the NK activity of PBL by tertiles, age-adjusted relative risk of cancer incidence (all sites) is 0.62 (95%CI, 0.38-1.03) and O.72 (0.45-1.16) for men with medium and high NK activity, respectively, taking the risk of those with low NK activity as reference ; 0.56 (0.31-1.01) and 0.52 (0.28-0.95) for women with medium and high NK activity, respectively ; 0.59 (0.40-0.87) and 0.63 (0.43-0.92) for both sexes with medium and high NK activity, respectively. Although NK activity was found to be associated with selected lifestyle factors, the results almost unchanged even after adjusting for these factors.The findings in our prospective cohort study were followed by a further study to compare the two different cytotoxicities of PBL (perforin/granzyme-dependent and Fas ligand-dependent) among 105 healthy individuals, along with measurement of NK cells, expression of KIR (killer-cell inhibitory receptor) and KAR (killer-cell activating receptor) on NK cells, and production of cytokines. We found that PBL showed a strong FasL-independent NK activity even towards the target cells which highly express MHC class I, and that this NK activity was well correlated to that measured in our cohort study using K562 as target cells..

我们通过一项前瞻性队列研究，在普通人群（共3625名40岁以上的个体）中调查了参与人类致癌的宿主-环境相互作用，使用了各种生物标志物和生活方式问卷。一项为期11年的随访调查发现，共192例癌症病例，表明外周血淋巴细胞（PBL）的NK（自然杀手）活性（以K562为靶细胞）在基线时通过同位素释放法评估，显示与癌症发病率呈负相关。将PBL的NK活性按位数分类，以低NK活性为参照，中NK活性和高NK活性男性的年龄调整相对癌症发病率（所有部位）分别为0.62 （95%CI, 0.38-1.03）和0.72 (0.45-1.16)；NK活性中高的女性分别为0.56（0.31-1.01）和0.52 (0.28-0.95)；NK活性中、高的两性分别为0.59（0.40 ~ 0.87）和0.63（0.43 ~ 0.92）。虽然NK活性被发现与选定的生活方式因素有关，但即使在调整这些因素后，结果几乎没有变化。在我们前瞻性队列研究的发现之后，我们进行了进一步的研究，比较了105名健康个体中PBL（穿孔素/颗粒酶依赖性和Fas配体依赖性）的两种不同的细胞毒性，同时测量了NK细胞，NK细胞上KIR（杀伤细胞抑制受体）和KAR（杀伤细胞激活受体）的表达，以及细胞因子的产生。我们发现PBL甚至对高度表达MHC I类的靶细胞也表现出很强的fasl独立NK活性，并且这种NK活性与我们使用K562作为靶细胞的队列研究中测量的NK活性有很好的相关性。