Kenji Suga

A number of epidemiological and clinical studies have revealed that excess body weight increases the risk of postmenopausal breast cancer and also adversely affects subsequent malignant progression. To elucidate the molecular mechanisms underlying these observations, we examined mRNA expression of various genes in normal (non‐cancerous) mammary gland and cancer tissue of Japanese patients with primary breast cancer, in association with their body mass index (BMI). On the basis of analysis of 106 breast cancer patients, we found that mRNA expression of insulin‐like growth factor I receptor (IGF‐IR) and insulin‐like growth factor II (IGF‐II) in the normal mammary gland showed a significant and positive association with increased BMI among postmenopausal patients. Furthermore, the positive association of increased BMI with IGF‐IR mRNA expression was also found in postmenopausal breast cancer tissue, while this association was not observed among premenopausal patients. In addition, increased mRNA expression of cyclin Dl and bcl‐2 was observed in association with increased mRNA levels of IGF‐IR among the patients regardless of menopausal status. These findings suggest that the molecular consequence of the increased BMI is the increased expression of IGF‐II and IGF‐IR, resulting in development of postmenopausal breast cancer and its progression mediated through modulation of the cell cycle and apoptosis.

Based on our prospective cohort study of healthy volunteers in a town in Saitama prefecture, Japan, we previously reported that drinking green tea prevents cancer. To apply our results to the general population, we conducted a Phase I trial with green tea tablets in 108 Japanese healthy volunteers for 6 months. Each volunteer took 15 green tea tablets per day, a total of 2.25 g of crude green tea extract or 337.5 mg of (-)-epigallocatechin gallate. The dose is equivalent to 10 cups of green tea per day. Effects of green tea tablets on volunteers were examined by various tests on blood samples, such as blood cell counts, serum lipids, hepatologic markers, and body iron; a questionnaire was also used to determine any symptoms experienced. The results of blood examination indicated that none of the volunteers experienced any strong adverse effects. Specifically, 24 volunteers (22%) complained of mild or moderate disorders, such as stomach discomfort or heartburn. Our study provided significant evidence that a Phase I clinical trial with green tea tablets is applicable to healthy Japanese for the purpose of cancer prevention.

The 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 drinking green tea acts protectively against cardiovascular and liver diseases.