Michinori Kabuto

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

Background:Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.Methods:Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.Results:Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.Conclusion:Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Helicobacter pylori, dietary factors, and atrophic gastritis in five Japanese populations with different gastric cancer mortality

In a cross-sectional study of 634 men aged 40 to 49 years, randomly selected from five areas of Japan with different rates of gastric cancer mortality, 121 men of 624 evaluated were diagnosed as having atrophic gastritis through serum pepsinogen I<70 ng/ml and the pepsinogen I (PGI)/pepsinogen II (PGII) ratio <3.0. We examined the relation of Helicobacter pylori (H. pylori) antibodies and dietary factors, including plasma level of antioxidant micronutrients, to the presence of atrophic gastritis. Presence of H. pylori IgG antibodies was associated with increased risk of atrophic gastritis (odds ratio [OR]=1.9, 95 percent confidence interval [CI]=1.1–3.3). As the level of plasma β-carotene increased, we found a steady decrease in the risk of atrophic gastritis (OR for second quartile = 0.7, third quartile = 0.6, fourth quartile = 0.4, with CI=0.2–0.8). Frequent intake of yellow vegetables also was associated with lower risk, while frequent intake of soybean products was related to increased risk. Although H. pylori antibodies, β-carotene level, and intake of soybean products were all significant in the multivariate analysis, these factors did not explain the differences in atrophic gastritis prevalence among the five regions. The analysis of these risk factors in relation to each pepsinogen marker showed that although both H. pylori infection and low plasma β-carotene were associated with the decreased level of serum PGI/II ratio, the former was derived from the increase of PGII, which is common in early stage of atrophic gastritis, and the latter from the decrease of PGI, which is specific to severe atrophic gastritis. This finding suggests that H. pylori infection is associated with the formation of atrophic gastritis, while β-carotene protects its advancement as well as formation.

Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone‐binding globulin in premenopausal Japanese women

Caffeine intake has been proposed to influence breast cancer risk. Its effect may be mediated by hormonal changes. The relationships between caffeine-containing beverages (coffee, green tea, black tea, oolong tea, and cola) and serum concentrations of estradiol and sex hormone-binding globulin were evaluated in 50 premenopausal Japanese women. Intakes of caffeine and caffeine-containing beverages were assessed by a semiquantitative food-frequency questionnaire. Blood samples were obtained from each woman on Days 11 and 22 of her menstrual cycle. High intakes of caffeinated coffee, green tea, and total caffeine were commonly correlated with increasing sex hormone-binding globulin on Days 11 and 22 of the cycle after controlling for potential confounders [Spearman correlation coefficients (r) ranged from 0.23 to 0.31]. Green tea but not caffeinated coffee intake was inversely correlated with estradiol on Day 11 of the cycle (r = -0.32, p = 0.04). Although the effect of caffeine cannot be distinguished from effects of coffee and green tea, consumption of caffeine-containing beverages appeared to favorably alter hormone levels associated with the risk of developing breast cancer.

Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women

We examined the cross-sectional relationship of soy product intake to serum concentrations of estradiol (E2) and sex hormone-binding globulin (SHBG) in 50 healthy premenopausal Japanese women. Intakes of soy products and various nutrients were estimated through a semiquantitative food-frequency questionnaire. Blood samples were drawn from each subject on Days 11 and 22 of her menstrual cycle. The intake of soy products was inversely correlated with E2 on Days 11 and 22 of the cycle after controlling for age, body mass index, cycle length, and intakes of total energy, fat, and crude fiber (r = -0.23, p = 0.08 and r = -0.32, p = 0.04, respectively). No significant correlation was observed between soy product intake and SHBG. There was a tendency for the intake of individual soy foods such as tofu and miso to be inversely correlated with E2 on Days 11 and 22 of the menstrual cycle. Miso intake was inversely significantly correlated with SHBG on Day 22 of the cycle (r = -0.36, p = 0.02). If the observed association is causal, our results suggest that the consumption of soy products lowers the risk of developing breast cancer risk modifying estrogen metabolism.

Childhood leukemia and magnetic fields in Japan: A case-control study of childhood leukemia and residential power-frequency magnetic fields in Japan

Residential power‐frequency magnetic fields (MFs) were labeled as a possible human carcinogen by the International Agency for Research on Cancer panel. In response to great public concern, the World Health Organization urged that further epidemiologic studies be conducted in high‐exposure areas such as Japan. We conducted a population‐based case‐control study, which covered areas inhabited by 54% of Japanese children. We analyzed 312 case children (0–15 years old) newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myelocytic leukemia (AML) in 1999–2001 (2.3 years) and 603 controls matched for gender, age and residential area. Weekly mean MF level was determined for the childs bedroom. MF measurements in each set of a case and controls were carried out as closely in time as possible to control for seasonal variation. We evaluated the association using conditional logistic regression models. The odds ratios for children whose bedrooms had MF levels of 0.4 μT or higher compared with the reference category (MF levels below 0.1 μT) was 2.6 (95% CI = 0.76–8.6) for AML + ALL and 4.7 (1.15–19.0) for ALL only. Controlling for some possible confounding factors did not alter the results appreciably. Even an analysis in which selection bias was maximized did not fully explain the association. Most of the leukemia cases in the highest exposure category had MF levels far above 0.4 μT. Our results provided additional evidence that high MF exposure was associated with a higher risk of childhood leukemia, particularly of ALL.

Prevalences of periodic limb movement-like and restless legs-like symptoms among Japanese adults.

Prevalences of periodic limb movement‐like and restless legs‐like symptoms among Japanese adults were investigated. The latter symptom was significantly associated with insomnia.

Associations of alcohol, height, and reproductive factors with serum hormone concentrations in postmenopausal Japanese women. Steroid hormones in Japanese postmenopausal women.

We measured serum levels of estradiol (E2), sex hormone-binding globulin (SHBG), progesterone, and dehydroepiandrosterone sulfate (DHEAS) in 61 postmenopausal women drawn from female residents in a community in Japan to evaluate the relationships between these hormone levels and potential breast cancer risk factors. The information on reproductive history, body size, alcohol use, and physical activity was obtained by means of a self-administered questionnaire. There was a significant trend in increasing E2 level with increasing height after taking account of age and body mass index (BMI) (p for trend = 0.04). BMI was inversely associated with SHBG level after controlling for age (p for trend = 0.01). Decreasing progesterone with increasing BMI was observed after controlling age and history of hysterectomy (P=0.05). Alcohol consumption was positively associated with E2 level and there was a strong linear trend after controlling for age, height, and BMI (p for trend=0.001). Trend for increasing DHEAS with alcohol consumption was also statistically significant after controlling for age and history of hysterectomy (p for trend=0.01). Reproductive factors as well as physical activity were not related to any of the hormone levels.

Fat and fiber intakes in relation to serum estrogen concentration in premenopausal Japanese women.

It has been implied that fat and fiber intakes influence breast cancer risk. The effects of these dietary factors may be mediated by hormonal changes. We evaluated the relationships between fat or fiber intake and serum concentration of estradiol (E2) or sex hormone-binding globulin in premenopausal women. In 1994 blood samples were collected from each of 50 premenopausal healthy Japanese women on Days 11 and 22 of the menstrual cycle. Nutrient intakes were assessed by food frequency questionnaire in which the subjects were asked about their diets during one year before the study. Each nutrient intake was categorized into tertile after adjustment for total energy. Linear regression models, including age and cycle length as covariates, were utilized to evaluate the association between the nutrient intakes and the hormone concentrations. A statistically significant trend was observed between increasing fat intake and increasing E2 on Day 11 of the cycle (p = 0.05). The positive trend for increasing sex hormone-binding globulin on Day 22 with fat intake was of borderline significance (p = 0.06). There was a statistically significant inverse trend for E2 on Day 11 of the cycle with fiber intake (p = 0.05). It was suggested that fat as well as fiber intake should affect the hormone status.

Serum ferritin and stomach cancer risk among a Japanese population.

Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970‐to‐1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset.

Effect of soy isoflavones on endometriosis: interaction with estrogen receptor 2 gene polymorphism.

Background: Progression of endometriosis is considered estrogen-dependent. Dietary soy isoflavones may affect the risk of endometriosis, and polymorphisms in estrogen receptor genes may modify this association. We examined associations among soy isoflavone intake, estrogen receptor 2 (ESR2) gene polymorphisms and risk of endometriosis. Methods: We recruited women age 20–45 years old who had consulted a university hospital for infertility in Tokyo, Japan in 1999 or 2000. A total of 138 eligible women were diagnosed laparoscopically and classified into 3 subgroups: control (no endometriosis), early endometriosis (stage I–II) and advanced endometriosis (stage III–IV). We measured urinary levels of genistein and daidzein as markers for dietary intake of soy isoflavones, and genotyped ESR2 gene RsaI polymorphisms. Results: Higher levels of urinary genistein and daidzein were associated with decreased risk of advanced endometriosis (P for trend = 0.01 and 0.06, respectively) but not early endometriosis. For advanced endometriosis, the adjusted odds ratio for the highest quartile group was 0.21 (95% confidence interval = 0.06–0.76) for genistein and 0.29 (0.08–1.03) for daidzein, when compared with the lowest group. Inverse associations were also noted between urinary isoflavones and the severity of endometriosis (P for trend = 0.01 for genistein and 0.07 for daidzein). For advanced endometriosis, ESR2 gene RsaI polymorphism appeared to modify the effects of genistein (P for interaction = 0.03). Conclusions: Dietary isoflavones may reduce the risk of endometriosis among Japanese women.