Kenji Suga

Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population

BACKGROUND One of the most critical questions in immunosurveillance is whether differences between individuals with regards to natural immunological host defence can predict future development of cancer. Although this question has so far remained open, there are clear indications of significant roles of several naturally cytotoxic lymphocytes in preventing the development of cancer. We began a prospective cohort study among a Japanese general population in 1986, using various immunological and biochemical markers. METHODS Natural cytotoxic activity of peripheral-blood mononuclear cells was assessed by isotope-release assay in 3625 residents of a Japanese population mostly older than 40 years of age, between 1986 and 1990. Immunological and biochemical markers were also measured, and participants were given a questionnaire on lifestyle. We did an 11-year follow-up survey of the cohort members looking at cancer incidence and death from all causes, and analysed the association between cytotoxic activity of peripheral-blood lymphocytes assessed at baseline and cancer incidence found in the subsequent follow-up. FINDINGS 154 cancer cases were used in the analysis. When we categorised the cytotoxic activity of peripheral-blood lymphocytes by tertiles, age-adjusted relative risk of cancer incidence (all sites) was 0.72 (95% CI 0.45-1.16) for men with high cytotoxic activity, and 0.62 (0.38-1.03) for men with medium cytotoxic activity, taking the risk of those with low cytotoxic activity as reference. For women with high cytotoxic activity relative risk was 0.52 (0.28-0.95), and for those with medium cytotoxic activity 0.56 (0.31-1.01). For both sexes with high and medium cytotoxic activity risk was 0.63 (0.43-0.92) and 0.59 (0.40-0.87), respectively. INTERPRETATION Our results indicate that medium and high cytotoxic activity of peripheral-blood lymphocytes is associated with reduced cancer risk, whereas low activity is associated with increased cancer risk suggesting a role for natural immunological host defence mechanisms against cancer.

Influence of Drinking Green Tea on Breast Cancer Malignancy among Japanese Patients

Inhibitory effects of green tea on carcinogenesis have been investigated in numerous laboratory studies using (–)‐epigallocatechin gallate (EGCG) or crude green tea extract, and there is also some epidemiologic evidence. Further, EGCG has been reported to inhibit the growth of cancer cells, lung metastasis in an animal model, and urokinase activity. In this study, we first examined the association between consumption of green tea prior to clinical cancer onset and various clinical parameters assessed at surgery among 472 patients with stage I, II, and III breast cancer. We found that increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones. Since these are potential prognostic factors, we then investigated the prognosis of breast cancer with special reference to consumption of green tea, in a follow‐up study of these patients. We found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer (P<0.05 for crude disease‐free survival); the recurrence rate was 16.7 or 24.3% among those consuming ≥5 cups or ≥4 cups per day, respectively, in a seven‐year follow‐up of stage I and II breast cancer, and the relative risk of recurrence was 0.564 (95% confidence interval, 0.350–0.911) after adjustment for other lifestyle factors. However, no improvement in prognosis was observed in stage III breast cancer. Our results indicate that increased consumption of green tea prior to clinical cancer onset is significantly associated with improved prognosis of stage I and II breast cancer, and this association may be related to a modifying effect of green tea on the clinical characteristics of the cancer.

Cancer inhibition by green tea.

Green tea is now an acknowledged cancer preventive in Japan. This paper discusses several important features of (-)-epigallocatechin gallate (EGCG), the main constituent of green tea and tea polyphenols. EGCG and other tea polyphenols inhibited growth of human lung cancer cell line, PC-9 cells with G2/M arrest. 3H-EGCG administered by p.o. intubation into mouse stomach revealed that small amounts of 3H-activity were found in various organs where EGCG and green tea extract had previously demonstrated their anticarcinogenic effects, such as skin, stomach, duodenum, colon, liver, lung and pancreas. Cancer onset of patients who had consumed over 10 cups of green tea per day was 8.7 years later among females and 3.0 years later among males, compared with patients who had consumed under three cups per day. The mechanisms of action of EGCG were briefly discussed with regard to inhibition of tumor necrosis factor-alpha (TNF-alpha) release.

Different expression patterns of Bcl-2 family genes in breast cancer by estrogen receptor status with special reference to pro-apoptotic Bak gene

Oncogenic and anti-apoptotic Bcl-2 is expressed much less in estrogen receptor α (ERα) negative breast cancers, which show more malignant phenotypes, than ERα-positive, indicating that some other Bcl-2 family member(s) are involved in the apoptotic balance of the cancer cells. We first analyzed mRNA expression of pro-apoptotic Bak and Bax along with that of anti-apoptotic Bcl-2 and Bcl-xL, using breast cancer specimens of 27 patients. Bak mRNA was expressed much less in ERα negative breast cancers, along with reduced expression of Bcl-2. Immunostaining of sections of 108 patients confirmed the observation. Next, stable transformants of MCF-7 cells with sense Bak expression vector showed fewer colonies in soft agar compared with the parental cells, while stable introduction of antisense Bak vector enhanced colony formation at lower estradiol concentrations. The reduction of Bak may play important roles in malignant development of breast cancer to acquire estrogen independency, counteracting the reduced Bcl-2. Cell Death and Differentiation (2000) 7, 439–446

Epidemiological Evidence for Prevention of Cancer and Cardiovascular Disease by Drinking Green Tea

Laboratory studies have revealed significant inhibitory effects of green tea extract or tea polyphenols against carcinogenesis in a wide variety of target organs of rodents. We have demonstrated the protective effect of green tea against cancer on the basis of a prospective cohort study in Saitama, Japan. Three results are presented: first, a 9-year follow-up survey on a total of 8552 individuals revealed later deaths from cancer among those patients consuming 10 or more cups of green tea a day; second, a reduction of age-adjusted cancer mortality rate was observed in the female population and male never-smokers consuming 10 or more cups a day; third, drinking large amounts of green tea exerted a preventive effect on cardiovascular disease, which was included in the same cohort study in terms of cross-sectional analysis on consumption of green tea and serum risk markers for the disease. Finally, the amount of (—)-epigallocatechin gallate intake, the main constituent of tea polyphenols, was estimated among a Japanese population with high consumption of green tea and was shown to be comparable to the amounts used in laboratory studies. These results strongly indicate that green tea can prevent both cancer and cardiovascular disease, which are the most important targets of preventive medicine for adults.

Drinking green tea prevents cardiovascular and liver diseases

AbstractThe association between consumption of green tea and various serum components in a Japanese population was studied, with special reference to the preventive effects of green tea against cardiovascular and liver diseases. Specially, 1,371 men aged over 40 years were surveyed on living habits, including daily consumption of green tea, and their peripheral blood samples were subjected to several biochemical assays. We first found that increased consumption of green tea was associated with decreased serum total cholesterol and triglyceride; increased proportion of high density lipoprotein cholesterol and decreased proportion of low density and very low density lipoprotein cholesterol, reflecting in a reduced atherogenic index. In addition, increased consumption of green tea, especially more than ten cups a day, was also related to decreased concentration of hepatological serum markers such as aspartate aminotransferase and alanine aminotransferase, and serum ferritin. These observations indicated that...