Kie Konishi

Soy isoflavone intake and stomach cancer risk in Japan: From the Takayama study: Isoflavone and Stomach Cancer Risk in Japan

Although several experimental studies suggested that soy isoflavone intake inhibits the growth of stomach cancer, previous epidemiological studies have observed inconsistent results. We evaluated the associations of soy or isoflavone intake with stomach cancer incidence after considering several lifestyle factors, including salt intake, in a population‐based prospective cohort study in Japan. Subjects were 14,219 men and 16,573 women aged 35 years or older in September 1992. Soy and isoflavone intakes, assessed with a validated food‐frequency questionnaire, were controlled for the total energy intake. Cancer incidence was mainly confirmed through regional population‐based cancer registries. Until March 2008, 441 men and 237 women developed stomach cancer. After adjustments for multiple confounders, a significantly decreased relative risk of stomach cancer was observed in the highest vs. lowest quartile of soy intake; the estimated hazard ratios were 0.71 (95% CI: 0.53, 0.96) for men (p for trend = 0.039) and 0.58 (95% CI: 0.36, 0.94) for women (p for trend = 0.003). Similar inverse associations between isoflavone intake and stomach cancer risk were also observed in women. Higher intake of non‐fermented soy foods was significantly associated with a lower risk of stomach cancer (p for trend: 0.022 in men and 0.005 in women), whereas there was no significant association between the intake of fermented soy foods and a risk of stomach cancer. These results suggest that a high intake of soy isoflavone, mainly nonfermented soy foods, have a protective effect against stomach cancer.

Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama study

BACKGROUND Whether soy intake is associated with a decreased risk of cardiovascular disease (CVD) remains unclear. A traditional Japanese soy food, natto, contains a potent fibrinolytic enzyme. However, its relation to CVD has not been studied. OBJECTIVE We aimed to examine the association of CVD mortality with the intake of natto, soy protein, and soy isoflavones in a population-based cohort study in Japan. DESIGN The study included 13,355 male and 15,724 female Takayama Study participants aged ≥35 y. At recruitment in 1992, each subject was administered a validated semiquantitative food-frequency questionnaire. Deaths from CVD were ascertained over 16 y. RESULTS A total of 1678 deaths from CVD including 677 stroke and 308 ischemic heart disease occurred during follow-up. The highest quartile of natto intake compared with the lowest intake was significantly associated with a decreased risk of mortality from total CVD after control for covariates: the HR was 0.75 (95% CI: 0.64, 0.88, P-trend = 0.0004). There were no significant associations between the risk of mortality from total CVD and intakes of total soy protein, total soy isoflavone, and soy protein or soy isoflavone from soy foods other than natto. The highest quartiles of total soy protein and natto intakes were significantly associated with a decreased risk of mortality from total stroke (HR = 0.75, 95% CI: 0.57, 0.99, P-trend = 0.03 and HR = 0.68, 95% CI: 0.52, 0.88, P-trend = 0.0004, respectively). The highest quartile of natto intake was also significantly associated with a decreased risk of mortality from ischemic stroke (HR = 0.67, 95% CI:0.47, 0.95, P-trend = 0.03). CONCLUSION Data suggest that natto intake may contribute to the reduction of CVD mortality.

Associations of acrylamide intake with circulating levels of sex hormones and prolactin in premenopausal Japanese women

Background: It has been hypothesized that alteration of hormone systems is involved in the carcinogenesis of acrylamide. The aim of the present study was to examine the cross-sectional associations between dietary acrylamide intake and sex hormone levels in premenopausal Japanese women. Methods: Study subjects were 393 women who had regular menstrual cycles less than 40 days long. Acrylamide intake was assessed with a food-frequency questionnaire and was based on acrylamide concentration reported from analyses of Japanese foods. We measured the plasma concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone–binding globulin, follicle-stimulating hormone, luteinizing hormone, and prolactin. Results: After controlling for age, the phase of the menstrual cycle, and other covariates, acrylamide intake was statistically significantly inversely associated with total and free estradiol levels and statistically significantly positively associated with follicle-stimulating hormone level. Total and free estradiol levels were 18.2% and 19.3% lower, respectively, in women in the highest quartile of acrylamide intake than in those in the lowest quartile of intake. Follicle-stimulating hormone levels were 23.5% higher in women in the highest quartile of acrylamide intake than in those in the lowest quartile of intake. Conclusion: The data suggest that acrylamide intake may alter estradiol and follicle-stimulating hormone levels. Impact: High estradiol levels have been associated with an increased risk of breast cancer. Although the results need confirmation, they highlight the need to investigate the relationships among dietary acrylamide, sex hormones, and breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(1); 249–54. ©2014 AACR.

Dietary Intakes of Glutamic Acid and Glycine Are Associated with Stroke Mortality in Japanese Adults

BACKGROUND Dietary intakes of glutamic acid and glycine have been reported to be associated with blood pressure. However, the link between intakes of these amino acids and stroke has not been studied. OBJECTIVE We aimed to examine the association between glutamic acid and glycine intakes and the risk of mortality from stroke in a population-based cohort study in Japan. METHODS The analyses included 29,079 residents (13,355 men and 15,724 women) of Takayama City, Japan, who were aged 35-101 y and enrolled in 1992. Their body mass index ranged from 9.9 to 57.4 kg/m(2). Their diets were assessed by a validated food frequency questionnaire. Deaths from stroke were ascertained over 16 y. RESULTS During follow-up, 677 deaths from stroke (328 men and 349 women) were identified. A high intake of glutamic acid in terms of a percentage of total protein was significantly associated with a decreased risk of mortality from total stroke in women after controlling for covariates; the HR (95% CI) for the highest vs. lowest quartile was 0.72 (0.53, 0.98; P-trend: 0.03). Glycine intake was significantly associated with an increased risk of mortality from total and ischemic stroke in men without history of hypertension at baseline; the HRs (95% CIs) for the highest vs. lowest tertile were 1.60 (0.97, 2.51; P-trend: 0.03) and 1.88 (1.01, 3.52; P-trend: 0.02), respectively. There was no association between animal or vegetable protein intake and mortality from total and any subtype of stroke. CONCLUSION The data suggest that glutamic acid and glycine intakes may be associated with risk of stroke mortality. Given that this is an initial observation, our results need to be confirmed.

Sleep Duration and the Risk of Mortality From Stroke in Japan: The Takayama Cohort Study

BACKGROUND Few studies have assessed the associations between sleep duration and stroke subtypes. We examined whether sleep duration is associated with mortality from total stroke, ischemic stroke, and hemorrhagic stroke in a population-based cohort of Japanese men and women. METHODS Subjects included 12 875 men and 15 021 women aged 35 years or older in 1992, who were followed until 2008. The outcome variable was stroke death (ischemic stroke, hemorrhagic stroke, and total stroke). RESULTS During follow-up, 611 stroke deaths (354 from ischemic stroke, 217 from hemorrhagic stroke, and 40 from undetermined stroke) were identified. Compared with 7 h of sleep, ≥9 h of sleep was significantly associated with an increased risk of total stroke and ischemic stroke mortality after controlling for covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were 1.51 (95% CI, 1.16-1.97) and 1.65 (95% CI, 1.16-2.35) for total stroke mortality and ischemic stroke mortality, respectively. Short sleep duration (≤6 h of sleep) was associated with a decreased risk of mortality from total stroke (HR 0.77; 95% CI, 0.59-1.01), although this association was of borderline significance (P = 0.06). The trends for total stroke and ischemic stroke mortality were also significant (P < 0.0001 and P = 0.0002, respectively). There was a significant risk reduction of hemorrhagic stroke mortality for ≤6 h of sleep as compared with 7 h of sleep (HR 0.64; 95% CI, 0.42-0.98; P for trend = 0.08). The risk reduction was pronounced for men (HR 0.31; 95% CI, 0.16-0.64). CONCLUSIONS Data suggest that longer sleep duration is associated with increased mortality from total and ischemic stroke. Short sleep duration may be associated with a decreased risk of mortality from hemorrhagic stroke in men.

Choline and Betaine Intakes Are Not Associated with Cardiovascular Disease Mortality Risk in Japanese Men and Women

BACKGROUND Dietary intakes of betaine and choline may reduce the risk of cardiovascular disease; however, epidemiologic evidence is limited. Seafood is a rich source of betaine and is a popular traditional food in Japan. OBJECTIVE We examined the associations of betaine and choline intakes with cardiovascular disease mortality in a population-based cohort study in Japan. METHODS Study subjects were 13,355 male and 15,724 female residents of Takayama City, Japan, who were aged ≥35 y and enrolled in 1992. Their diets were assessed by a validated food frequency questionnaire. Deaths from coronary heart disease and stroke were identified from death certificates over 16 y. Multivariable-adjusted HRs were computed by using Cox regression models. RESULTS During follow-up, we documented 308 deaths from coronary heart disease and 676 deaths from stroke (393 from ischemic and 153 from hemorrhagic strokes). Compared with the lowest quartile, the second, third, and highest quartiles of betaine intake were significantly associated with a decreased risk of mortality from coronary heart disease in men after controlling for covariates. The HRs were 0.58 (95% CI: 0.36, 0.93), 0.62 (95% CI: 0.39, 0.998), and 0.60 (95% CI: 0.37, 0.97), respectively. The trend was not statistically significant (P = 0.08). There was no significant association between betaine intake and the risk of mortality from ischemic stroke. In women, betaine intake was unrelated risk of mortality from coronary heart disease and stroke (P = 0.32 and 0.73, respectively, for interaction by sex). There was no significant association between choline intake and cardiovascular disease mortality risk in men or women. CONCLUSION Overall, we found no clear evidence of significant associations between choline and betaine intakes and cardiovascular disease mortality risk in Japanese men and women.

Alcohol Intake During Pregnancy and Offspring's Atopic Eczema Risk

BACKGROUND Although alcohol consumption has been suggested to have an effect on the immune system, it is unknown whether alcohol consumption has a role in developing allergic diseases. We aimed to examine the associations of total alcohol intake during pregnancy with the risks of childhood asthma and atopic eczema in a birth cohort in Japan. METHODS Pregnant women were recruited at a maternal clinic from May 2000 to October 2001. The children who were born to these mothers were followed until November 2007. Total alcohol intake, including alcohol as a cooking ingredient, was assessed using 5-day dietary records. Mother reports of physician-diagnosed asthma and atopic eczema were annually obtained from the questionnaires. Asthma assessed by the American Thoracic Society Division of Lung Diseases questionnaire and atopic eczema assessed by International Study of Asthma and Allergies in Childhood questions were also obtained in 2007. A total of 350 children participated in the follow-up survey. RESULTS Maternal total alcohol intake during pregnancy was associated with increased risks of atopic eczema before age 3. The positive association with atopic eczema was also observed when it was defined as before age 5. In the high versus the low tertile of maternal total alcohol intake, the estimated hazard ratios (HRs) of childs eczema were 1.90 (95% CI: 0.96 to 3.76) before age 3 and 1.74 (95% CI: 0.93 to 3.24) before age 5, respectively. The estimated HRs of childs asthma before age 3 was 1.61 (95% CI: 0.70 to 3.69) in the high versus the low of maternal total alcohol intake and 2.11 (95% CI: 0.93 to 4.81) among children having drinking mothers versus nondrinking mothers in pregnancy, although maternal alcohol intake during pregnancy was not significantly associated with the risk of asthma before age 5. CONCLUSIONS Alcohol consumption during pregnancy might have an effect on developing atopic eczema in offspring.

Sleep duration, nightshift work, and the timing of meals and urinary levels of 8-isoprostane and 6-sulfatoxymelatonin in Japanese women

ABSTRACT It has been hypothesized that disruption of circadian rhythms affects human health. Shift work and sleep deprivation are thought to disrupt the normal light–dark cycle, although the disruption due to shiftwork may be dependent on sleep deprivation. Both conditions have been suggested to be associated with an increased risk of cardiometabolic disorders. Non-photic environmental factors, such as the timing of eating, are also thought to regulate circadian rhythm and thus, may have effects on health, but the evidence from human studies is scarce. Oxidative stress is a risk factor of cardiometabolic disorders. Some laboratory studies suggest an involvement of circadian clock genes in the regulation of the redox system. The present study aimed to examine the association of sleeping habits, nightshift work, and the timing of meals with urinary levels of 8-isoprostane, a marker of oxidative stress, and 6-sulfatoxymelatonin, the principal metabolite of melatonin. Study subjects were 542 women who had previously attended a breast cancer mass screening in a community in Japan. Information on bedtimes and wake-up times, history of nightshift work, and the timing of meals was obtained by a self-administered questionnaire. The 8-isoprostane and 6-sulfatoxymelatonin were measured using the first morning void of urine and expressed per mg of creatinine. The geometric mean of 8-isoprostane levels was 12.1% higher in women with ≤6 hours of sleep than that in those with >8 hours of sleep on weekdays, and longer sleep duration on weekdays was significantly associated with lower urinary levels of 8-isoprostane after controlling for covariates (p for trend = 0.04). Women who were currently working the nightshift had a 33.3% higher geometric mean of 8-isoprostane levels than those who were not working nightshift (p = 0.03). Urinary 6-sulfatoxymelatonin levels were unrelated to sleep habits or nightshift work. Women who ate breakfast at irregular times had a 19.8% higher geometric mean of 8-isoprostane levels than those who ate breakfast at a regular time or who did not eat (p = 0.02). Women who ate nighttime snacks at irregular times had a 16.2% higher geometric mean of 8-isoprostane levels than those who did not eat nighttime snacks or who ate nighttime snacks at a regular time (p = 0.003). Among women who ate dinner at a regular time, earlier times for dinner were associated with higher 8-isoprostane and 6-sulfatoxymelatonin levels (p values for trends were 0.01 and 0.02, respectively). However, the times of dinner and nighttime snack are overlapping, and the time of last meal of the day was not associated with 8-isoprostane and 6-sulfatoxymelatonin levels. The time of breakfast or lunch was not associated with these biomarkers among women who ate the meal at regular times. Disturbing the rhythmicity of daily life may be associated with oxidative stress.

Association of alcohol consumption with the risk of stomach cancer in a Japanese population: a prospective cohort study

Biological studies have provided confirmation of alcohol-related carcinogenesis in the stomach, but the association between alcohol consumption and the risk of stomach cancer remains controversial. We aimed to investigate whether quantitative alcohol intake is associated with the risk of stomach cancer in a large prospective cohort study among a Japanese population. Study participants included 30 714 participants (14 171 men and 16 543 women) aged 35 years or older, who were enrolled in the Takayama study launched on 1 September 1992. Alcohol consumption was assessed quantitatively using a validated food frequency questionnaire. According to alcohol intake (g/day), male participants were classified into quartile groups: Q1, Q2, Q3, or Q4. Female participants were classified into three groups: nondrinkers, and drinkers below or above the median alcohol level. We estimated the hazard ratios and 95% confidence intervals (CIs) for stomach cancer adjusted for age, smoking, BMI, education, total energy intake, salt intake, physical activity, and medical history of diabetes mellitus for each alcohol intake group using the Cox proportional hazards regression model. By the end of March 2008, a total of 678 participants had been diagnosed with stomach cancer. For men, the multivariate-adjusted HRs of stomach cancer for Q2, Q3, and Q4 relative to Q1 were 1.39 (95% CI: 1.07–1.81), 1.35 (95% CI: 1.02–1.79), and 1.38 (95% CI: 1.02–1.87), respectively. In women, no associations were observed. These data suggest that alcohol consumption could be associated with an increased risk of stomach cancer among Japanese men.

Meat consumption and colorectal cancer risk in Japan: The Takayama study.

Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population‐based prospective cohort study in Japan. Participants were 13 957 men and 16 374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population‐based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. From September 1992 to March 2008, 429 men and 343 women developed colorectal cancer. After adjustments for multiple confounders, a significantly increased relative risk of colorectal cancer was observed in the highest versus lowest quartile of the intake of total and red meat among men; the estimated hazard ratios were 1.36 (95% CI: 1.03, 1.79) for total meat (P for trend = 0.022), and 1.44 (95% CI: 1.10, 1.89) for red meat (P for trend = 0.009). A positive association between processed meat intake and colon cancer risk was also observed in men. There was no significant association between colorectal cancer and meat consumption in women. These results suggest that the intake of red and processed meat increases the risk of colorectal or colon cancer among Japanese men. Abstaining from excessive consumption of meat might be protective against developing colorectal cancer.