Jun Nagano

Vegetables and fruit intake and cancer mortality in the Hiroshima/Nagasaki Life Span Study

The association between green-yellow vegetables and fruit consumption and risk of cancer death was investigated in a prospective study of 38 540 men and women who were atomic-bomb survivors in Hiroshima and Nagasaki, Japan. Study participants completed a dietary questionnaire in 1980–1981 and were followed-up for cancer deaths until March 1998, during which time 3136 cancer deaths were identified. Daily or almost daily fruit consumption was associated with a significant 12% reduction in total cancer mortality (RR=0.88; 95% CI, 0.80–0.96 for daily intake compared with intake once per week or less). Daily or almost daily green-yellow vegetables consumption was associated with a marginally significant 8% reduction in total cancer mortality (0.92; 0.94–1.01). Green-yellow vegetables consumption was associated with a significant reduction in liver cancer mortality (0.75; 0.60–0.95). Fruit consumption was associated with a significantly reduced risk of stomach cancer and lung cancer mortality (0.80; 0.65–0.98). Green-yellow vegetables and fruit consumption was associated with a reduction in oesophageal cancer, but these associations were not statistically significant. Neither green-yellow vegetables nor fruit consumption was associated with colorectal cancer or breast cancer mortality. These results support the evidence that daily consumption of fruit and vegetables reduces the risk of total cancer, and specifically cancers of the stomach, liver, and lung.

A prospective study of green tea consumption and cancer incidence, Hiroshima and Nagasaki (Japan)

AbstractObjectives: Laboratory and animal studies have shown a protective effect of green tea on cancer of different sites, but epidemiological evidence is limited and inconclusive. This prospective study in Japan examined the association between green tea consumption and cancer incidence. Methods: Subjects were 38,540 people (14,873 men, mean age 52.8 years; 23,667 women, mean age 56.8 years) who responded to a mail survey carried out between 1979 and 1981. A self-administered questionnaire ascertained consumption frequency of green tea using precoded answers (never, once per day, twice to four times per day, and five or more times per day). Follow-up continued until 31 December 1994. The study analyzed solid cancers (n = 3881); hematopoietic cancers (188); cancers of all sites combined (4069); and cancer of specific sites with more than 100 cases, i.e. stomach (901), colon (432), rectum (193), liver (418), gallbladder (122), pancreas (122), lung (436), breast (281), and bladder (122). Poisson regression was used to allow for city, gender, age, radiation exposure, smoking status, alcohol drinking, body-mass index, education level, and calendar time. Results: Green tea consumption was virtually unrelated to incidence of cancers under study. The relative risks of all cancers for those consuming green tea twice to four times per day and five or more times per day were 1.0 (95% confidence interval 0.91–1.1) and 0.98 (0.88–1.1), respectively, as compared with those consuming green tea once per day or less. Conclusion: Our findings do not provide evidence that regular green tea consumption is related to reduced cancer risks.

Bladder‐cancer incidence in relation to vegetable and fruit consumption: A prospective study of atomic‐bomb survivors

We examined the relation between consumption of 22 dietary items and subsequent bladder‐cancer incidence in a cohort of atomic‐bomb survivors in Japan. Subjects were 38,540 people (14,873 men and 23,667 women) who responded to a mail survey carried out between 1979 and 1981 and who had no known cancer diagnosed before the start of follow‐up (1 January 1980 for men, 1 February 1981 for women). Consumption frequencies for 22 dietary items were ascertained with pre‐coded answers. As of the end of 1993, there were 114 (83 men and 31 women) incident cases of bladder cancer among 450,326 person‐years at risk. Statistical analysis was done using Poisson regression for grouped survival data. Consumption of green‐yellow vegetables and fruit were protectively associated with risk. Adjusted for gender, age, radiation exposure, smoking status, educational level, body‐mass index and calendar time, the relative risk (RR) for those consuming green‐yellow vegetables 2–4 times per week and almost everyday was 0.62 [95% confidence interval (CI) 0.39–0.98] and 0.54 (95% CI 0.30–0.94) respectively, as compared with those consuming once per week or less. The corresponding RR for fruit consumption was 0.50 (0.30–0.81) and 0.62 (0.39–0.99) respectively. Chicken consumption was unexpectedly associated with decreased risk, but additional adjustment for consumption did not change the relation of green‐yellow vegetables or of fruit to risk. The consumption of the other dietary items, including meat and green tea, was not related to risk. The findings add to evidence that high consumption of vegetables and fruit are protective against bladder cancer. Int. J. Cancer 86:132–138, 2000.

Vegetable and Fruit Intake and Stroke Mortality in the Hiroshima/Nagasaki Life Span Study

Background and Purpose— Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately. Methods— A prospective cohort study of 40 349 Japanese men and women was initiated in 1980–1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered. Results— A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction. Conclusions— Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.

A prospective study of diet and prostate cancer in Japanese men.

Background and aims. It has been hypothesized that some aspect of a traditional ‘Asian’ diet, that is low in animal products and high in soya, may be associated with a reduced risk of prostate cancer. This study aimed to examine the association between dietary intake and prostate cancer risk among 18,115 men in Hiroshima and Nagasaki, Japan, using prospective data from the Life Span Study. Methods: Subjects completed a food-frequency questionnaire at baseline (1963, 1965 and/or 1979) and were followed for incident prostate cancer until the end of 1996. During this time, 196 incident prostate cancer cases were identified after 252,602 person-years of observation. Poisson regression was used to calculate incidence rates for each dietary factor after adjustment for age, calendar period, city of residence, radiation dose and education level. Results: Fish intake was significantly associated with an increased risk of prostate cancer; men who consumed fish more than four times per week had a 54 increased risk of developing prostate cancer compared with men who ate fish less than twice per week (RR=1.54; 95 CI, 1.03–2.31). No other food items, including soya products, were significantly associated with prostate cancer risk. Conclusions: These data suggest that dietary factors may not be strong determinants of prostate cancer in these Japanese men, although the increased risk associated with a high consumption of fish warrants further study.

Meat,fish and fat intake in relation to subsite-specific risk of colorectal cancer.The Fukuoka Colorectal Cancer Study

High intake of red meat has been associated with increased risk of colorectal cancer in Western countries. There has been much interest in the role of n‐3 polyunsaturated fatty acids (PUFA) in colorectal cancer prevention, but epidemiological findings are limited and inconsistent. The objective of our study was to examine associations of meat, fish and fat intake with risk of colorectal cancer, paying particular attention to the subsite within the colorectum. Data were from the Fukuoka Colorectal Cancer Study, a population‐based case‐control study, covering 782 cases and 793 controls. Diet was assessed by interview, using newly developed personal‐computer software for registering semiquantitative food frequencies. The intake of beef/pork, processed meat, total fat, saturated fat or n‐6 PUFA showed no clear association with the overall or subsite‐specific risk of colorectal cancer. There was an almost significant inverse association between n‐3 PUFA and the risk of colorectal cancer; the covariate‐adjusted odds ratio for the highest (median 3.94 g/day) versus lowest (median 1.99 g/day) quintile of energy‐adjusted intake was 0.74 (95% confidence interval 0.52–1.06, trend P = 0.050). The consumption of fish and fish products was similarly inversely related to the risk although the association was not statistically significant. These associations were more evident for distal colon cancer; adjusted odds ratio for the highest versus lowest quintile of n‐3 PUFA intake was 0.56 (95% confidence interval 0.34–0.92, trend P = 0.02). Our findings do not support the hypothesis that consumption of red meat increases colorectal cancer risk but do suggest that high intake of fish may decrease the risk, particularly of distal colon cancer. (Cancer Sci 2007; 98: 590–597)

Animal Protein, Animal Fat, and Cholesterol Intakes and Risk of Cerebral Infarction Mortality in the Adult Health Study

Background and Purpose— A traditional diet that is poor in animal products is thought to explain the high rate of stroke in Asian populations. The purpose of the present study was to examine the effect of a diet rich in animal protein, animal fat, and cholesterol on the risk of cerebral infarction mortality in a Japanese population. Methods— A prospective study of 3731 Japanese men and women aged 35 to 89 years was conducted from 1984 to 2001. Nutrient intake was estimated at baseline from the responses to a 24-hour diary. During the follow-up period, cases of cerebral infarction deaths (as entered on death certificates) were monitored. Results— During the follow-up period, 60 deaths were attributed to cerebral infarction. A high intake of animal fat and cholesterol was significantly associated with a reduced risk of cerebral infarction death. The risk was reduced by 62% (CI, 82% to 18%) for those in the third tertile of animal fat intake, compared with those in the first tertile, with a significant linear dose-response relationship (P =0.0073). The risk of death from infarction was reduced by 63% (CI, 82% to 22%) in the high cholesterol consumption group, compared with the low consumption group. A significant linear dose–response relationship was observed. Animal protein was not significantly associated with infarction mortality after adjustment for animal fat and cholesterol. Conclusions— This study suggests that in Japan, where animal product intake is lower than in Western countries, a high consumption of animal fat and cholesterol was associated with a reduced risk of cerebral infarction death.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: the Fukuoka Colorectal Cancer Study.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated the relation of MTHFR C677T and A1298C polymorphisms to colorectal cancer in a case‐control study in Fukuoka, Japan. The subjects comprised 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly in the study area. The genotype was determined by the PCR‐RFLP method using genomic DNA extracted from buffy coat. Alcohol use was ascertained by in‐person interview. Statistical adjustment was made for gender, age class, area, and alcohol use. The MTHFR 677TT genotype was associated with a statistically significant decrease in the risk with an adjusted odds ratio of 0.69 (95% confidence interval 0.51–0.93) compared with the 677CC and 677CT combined, and the decrease was most evident in individuals with no alcohol consumption. While the A1298C polymorphism showed no measurable association with the overall risk of colorectal cancer, the 1298CC genotype was associated with a statistically significant increase in the risk when alcohol consumption was high, and was also associated with an approximately 2‐fold increase in the risk of each of proximal and distal colon cancer. The findings add to evidence that individuals with the MTHFR 677TT genotype have a decreased risk of colorectal cancer in the absence of folate depletion, suggesting a protective role of folate by ensuring a sufficient thymidylate pool for DNA synthesis. Because very few individuals had the 1298CC genotype, the findings regarding the A1298C polymorphism need careful interpretation and confirmation in larger studies.

Calcium, Dairy Foods, Vitamin D, and Colorectal Cancer Risk: The Fukuoka Colorectal Cancer Study

Epidemiologic evidence supporting a protective role of calcium and vitamin D in colorectal carcinogenesis has been accumulating in Western populations, but it is limited in Asian populations, whose intake of calcium is relatively low. We investigated the association of intakes of these nutrients with colorectal cancer risk in Japanese. Study subjects were participants of a large-scale case-control study in Fukuoka, Japan. Diet was assessed through interview regarding 148 dietary items by showing typical foods or dishes on the display of a personal computer. In a multivariate analysis adjusting for potential confounding variables, calcium intake was significantly, inversely associated with colorectal cancer risk (P for trend = 0.01); the odds ratio for the highest versus lowest quintile of calcium intake was 0.64 (95% confidence interval, 0.45-0.93). Higher levels of dietary vitamin D were significantly associated with decreased risk of colorectal cancer among those who had fewer chances of sunlight exposure at work or in leisure (P for trend = 0.02). A decreased risk of colorectal cancer associated with high calcium intake was observed among those who had higher levels of vitamin D intake or among those who had a greater chance of daily sunlight exposure, but not among those with medium or lower intake of vitamin D or among those with potentially decreased sunlight exposure. These results add to support for a joint action of calcium and vitamin D in the prevention of colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2800–7)

Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

BackgroundIt is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism.MethodsWe used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat.ResultsIn comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and ≥800 cigarette-years were 0.65 (95% confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with ≥400 cigarette-years (OR 1.60, 95% CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorectal cancer, showing a nearly statistically significant (Pinteraction = 0.06) or significant interaction (Pinteraction = 0.02). The composite genotypes of these two polymorphisms, however, showed no measurable interaction with cigarette smoking in relation to colorectal cancer risk.ConclusionsCigarette smoking may be associated with increased risk of rectal cancer, but not of colon cancer. The observed interactions between CYP1A1 and GSTT1 polymorphisms warrant further confirmation.