AKAGI Kiwamu SAITAMA CANCER CENTER RESEARCH INSTITUTE, 研究所, 研究員 (30244114)
MATSUYAMA Satoru SAITAMA CANCER CENTER RESEARCH INSTITUTE, 研究所, 研究員 (90311373)
IMAI Kazue SAITAMA CANCER CENTER RESEARCH INSTITUTE, 研究所, 主任研究員 (80260230)
EGUCHI Hidetaka SAITAMA CANCER CENTER RESEARCH INSTITUTE, 研究所, 研究員 (00260232)
|Budget Amount *help
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1999: ¥10,000,000 (Direct Cost: ¥10,000,000)
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..