Taichi Shimazu

Obesity and risk of cancer in Japan

We conducted a population‐based prospective cohort study in Japan to examine the relationship between body mass index (BMI) and the risk of incidence of any cancer and of cancer at individual sites. Body mass index was calculated from self‐administered body weight and height at baseline. Relative risks (RR) and 95% confidence intervals (CI) were calculated in multivariate proportional‐hazards models. Among 27,539 persons (15,054 women and 12,485 men) aged 40 years or older who were free of cancer at enrollment in 1984, 1,672 (668 women and 1,004 men) developed cancer during 9 years of follow‐up. In women, after adjustment for potential confounders, the RR of all cancers associated with different BMI, relative to a BMI of 18.5–24.9, were 1.04 (95% CI = 0.85–1.27) for BMI = 25.0–27.4, 1.29 (1.00–1.68) for BMI = 27.5–29.9 and 1.47 (1.06–2.05) for BMI ≥30.0 (p for trend = 0.007). Higher BMI was also significantly associated with higher risk of cancers of the colorectum, breast (postmenopausal), endometrium and gallbladder in women. In men, we observed significantly increased all‐cancer risk among only never‐smokers. Overweight and obesity could account for 4.5% (all subjects) or 6.2% (never‐smokers) of the risk of any cancer in women and −0.2% (all subjects) or 3.7% (never‐smokers) in men. The value for women was within the range among women reported from Western populations (3.2%–8.8%). Our data demonstrate that excess weight is a major cancer risk among Japanese women.

Coffee consumption and the risk of primary liver cancer: Pooled analysis of two prospective studies in Japan

Although case‐control studies suggested that coffee consumption is associated with a decreased risk of liver cancer, no prospective cohort study has been carried out. To examine the association between coffee consumption and the risk of liver cancer, we conducted a pooled analysis of data available from 2 cohort studies in Japan. A self‐administered questionnaire about the frequency of coffee consumption and other health habits was distributed to 22,404 subjects (10,588 men and 11,816 women) in Cohort 1 and 38,703 subjects (18,869 men and 19,834 women) in Cohort 2, aged 40 years or more, with no previous history of cancer. We identified 70 and 47 cases of liver cancer among the subjects in Cohort 1 (9 years of follow‐up with 170,640 person‐years) and Cohort 2 (7 years of follow‐up with 284,948 person‐years), respectively. We used Cox proportional hazards regression analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of liver cancer incidence. After adjustment for potential confounders, the pooled RR (95% CI) of drinking coffee never, occasionally and 1 or more cups/day were 1.00 (Reference), 0.71 (0.46–1.09) and 0.58 (0.36–0.96), respectively (p for trend = 0.024). In the subgroup of subjects with a history of liver disease, we found a significant inverse association between coffee consumption and the risk of liver cancer. Our findings support the hypothesis that coffee consumption decreases the risk of liver cancer. Further studies to investigate the role of coffee in prevention of liver cancer among the high‐risk population are needed.

The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands

Instructive mechanisms are present for induction of DNA methylation, as shown by methylation of specific CpG islands (CGIs) by specific inducers and in specific cancers. However, instructive factors involved are poorly understood, except for involvement of low transcription and trimethylation of histone H3 lysine 27 (H3K27me3). Here, we used methylated DNA immunoprecipitation (MeDIP) combined with a CGI oligonucleotide microarray analysis, and identified 5510 and 521 genes with promoter CGIs resistant and susceptible, respectively, to DNA methylation in prostate cancer cell lines. Expression analysis revealed that the susceptible genes had low transcription in a normal prostatic epithelial cell line. Chromatin immunoprecipitation with microarray hybridization (CHiP-chip) analysis of RNA polymerase II (Pol II) and histone modifications showed that, even among the genes with low transcription, the presence of Pol II was associated with marked resistance to DNA methylation (OR = 0.22; 95% CI = 0.12-0.38), and H3K27me3 was associated with increased susceptibility (OR = 11.20; 95% CI = 7.14-17.55). The same was true in normal human mammary epithelial cells for 5430 and 733 genes resistant and susceptible, respectively, to DNA methylation in breast cancer cell lines. These results showed that the presence of Pol II, active or stalled, and H3K27me3 can predict the epigenetic fate of promoter CGIs independently of transcription levels.

Consumption of n-3 Fatty Acids and Fish Reduces Risk of Hepatocellular Carcinoma

BACKGROUND & AIMS Fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Although consumption of fish and n-3 PUFA has been reported to protect against the development of some types of cancer, little is known about its association with hepatocellular carcinoma (HCC). METHODS We investigated the association between fish and n-3 PUFA consumption and HCC incidence (n = 398) in a population-based prospective cohort study of 90,296 Japanese subjects (aged, 45-74 y). Hazard ratios and 95% confidence intervals (CIs) for the highest vs the lowest quintile were estimated from multivariable adjusted Cox proportional hazards regression models. We also conducted subanalyses of subjects with known hepatitis B virus (HBV) or hepatitis C virus (HCV) status, and of subjects who were anti-HCV and/or hepatitis B surface antigen positive. All tests of statistical significance were 2-sided. RESULTS Among all subjects, consumption of n-3 PUFA-rich fish and individual n-3 PUFAs was associated inversely with HCC, in a dose-dependent manner. Hazard ratios for the highest vs lowest quintiles were 0.64 (95% CI, 0.42-0.96) for n-3 PUFA-rich fish, 0.56 (95% CI, 0.36-0.85) for EPA, 0.64 (95% CI, 0.41-0.98) for DPA, and 0.56 (95% CI, 0.35-0.87) for DHA. These inverse associations were similar irrespective of HCV or HBV status. CONCLUSIONS Consumption of n-3 PUFA-rich fish or n-3 PUFAs, particularly EPA, DPA, and DHA, appears to protect against the development of HCC, even among subjects with HBV and/or HCV infection.

Coffee Consumption and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Japanese Women

Coffee contains various compounds that have recently been reported to exert beneficial health effects. However, the conclusion of its relation with mortality has not yet been reached. In this study, we aimed to investigate the associations between coffee consumption and all-cause and cause-specific mortality in Japan. We included 37,742 participants (18,287 men and 19,455 women) aged 40-64 y without a history of cancer, myocardial infarction, or stroke at baseline in our analysis, based on the Miyagi Cohort Study initiated in 1990. The outcomes were mortality due to all causes, cardiovascular disease (CVD), and cancer. During the 10.3 y of follow-up, 2454 participants died, including 426 due to CVD and 724 due to cancer. In women, the multivariate hazard ratios (HR) (95% CI) for all-cause mortality in participants who drank coffee never, occasionally, 1-2 cups (150-300 mL)/d, and > or =3 cups/d were 1.00, 0.88 (0.73-1.06), 0.82 (0.66-1.02), and 0.75 (0.53-1.05), respectively (P-trend = 0.04). For CVD mortality in women, the multivariate HR (95% CI) were 1.00, 0.56 (0.36-0.86), 0.48 (0.29-0.80), and 0.45 (0.20-1.03), respectively (P-trend = 0.006). Of the specific CVD diseases, there was a strong inverse association between coffee consumption and mortality due to coronary heart disease (CHD) in women (P-trend = 0.02) but not in men. Death due to cancer was not associated with coffee consumption in either men or women, except for colorectal cancer in women. Our results suggest that coffee may have favorable effects on morality due to all causes and to CVD, especially CHD, in women.

Alcohol Drinking and Colorectal Cancer in Japanese: A Pooled Analysis of Results from Five Cohort Studies

Colorectal cancer is an alcohol-related malignancy; however, the association appears to be stronger among Asian populations with a relatively high prevalence of the slow-metabolizing aldehyde dehydrogenase variant. To examine the association between alcohol consumption and colorectal cancer in Japanese, the authors analyzed original data from five cohort studies that measured alcohol intake using validated questionnaires at baseline. Hazard ratios were calculated in the individual studies, with adjustment for a common set of variables, and then combined using a random-effects model. During 2,231,010 person-years of follow-up (ranging variously from 1988 to 2004), 2,802 colorectal cancer cases were identified. In men, multivariate-adjusted pooled hazard ratios for alcohol intakes of 23-45.9 g/day, 46-68.9 g/day, 69-91.9 g/day, and > or =92 g/day, compared with nondrinking, were 1.42 (95% confidence interval (CI): 1.21, 1.66), 1.95 (95% CI: 1.53, 2.49), 2.15 (95% CI: 1.74, 2.64), and 2.96 (95% CI: 2.27, 3.86), respectively (p for trend < 0.001). The association was evident for both the colon and the rectum. A significant positive association was also observed in women. One fourth of colorectal cancer cases in men were attributable to an alcohol intake of > or =23 g/day. An alcohol-colorectal cancer association seems to be more apparent in Japanese than in Western populations. Whether this difference can be ascribed to genetic or environmental factors needs to be clarified.

Consumption of sodium and salted foods in relation to cancer and cardiovascular disease: the Japan Public Health Center-based Prospective Study.

BACKGROUND Although the influence of salt, per se, on the risk of cancer or cardiovascular disease (CVD) might differ from that of salt-preserved foods, few studies have simultaneously examined the effects of sodium and salted foods on the risk of either cancer or CVD. OBJECTIVE We simultaneously examined associations between sodium and salted food consumption and the risk of cancer and CVD. DESIGN During 1995-1998, a validated food-frequency questionnaire was administered to 77,500 men and women aged 45-74 y. During up to 598,763 person-years of follow-up until the end of 2004, 4476 cases of cancer and 2066 cases of CVD were identified. RESULTS Higher consumption of sodium was associated with a higher risk of CVD but not with the risk of total cancer: multivariate hazard ratios for the highest compared with lowest quintiles of intake were 1.19 (95% CI: 1.01, 1.40; P for trend: 0.06) for CVD and 1.04 (95% CI: 0.93, 1.16; P for trend: 0.63) for total cancer. Higher consumption of salted fish roe was associated with higher risk of total cancer, and higher consumption of cooking and table salt was associated with higher risk of CVD. Similar results were seen for the risk of gastric or colorectal cancer and stroke. CONCLUSIONS Sodium intake as a whole salt equivalent may not increase the risk of cancer but may increase that of CVD. In contrast, salted food intake may increase the risk of cancer. Our findings support the notion that sodium and salted foods have differential influences on the development of cancer and CVD.

Effect of Coffee and Green Tea Consumption on the Risk of Liver Cancer: Cohort Analysis by Hepatitis Virus Infection Status

In spite of their anticarcinogenic potential, the effect of coffee and green tea consumption on the risk of liver cancer has not been clarified prospectively in consideration of hepatitis C (HCV) and B virus (HBV) infection. We examined whether coffee and green tea consumption was associated with a reduced risk of liver cancer by hepatitis virus infection status in the Japan Public Health Center-Based Prospective Study Cohort II. A total of 18,815 subjects ages 40 to 69 years participating in a questionnaire and health checkup survey in 1993 to 1994 were followed for the incidence of liver cancer through 2006. A total of 110 cases of liver cancer were newly documented. Hazard ratios for coffee and green tea consumption categories were calculated with a Cox proportional hazards model. Compared with almost never drinkers, increased coffee consumption was associated with a reduced risk of liver cancer in all subjects (hazard ratio for <1, 1-2, and ≥3 cups/d; Ptrend = 0.67, 0.49, 0.54, and 0.025). A similar risk tendency was observed in those with either or both HCV and HBV infection. In contrast, no association was observed between green tea consumption and the risk of liver cancer in all subjects. Our results suggest that coffee consumption may reduce the risk of liver cancer regardless of HCV and HBV infection status, whereas green tea may not reduce this risk.(Cancer Epidemiol Biomarkers Prev 2009;18(6):1746–53)

Attributable causes of cancer in Japan in 2005—systematic assessment to estimate current burden of cancer attributable to known preventable risk factors in Japan

BACKGROUND To contribute to evidence-based policy decision making for national cancer control, we conducted a systematic assessment to estimate the current burden of cancer attributable to known preventable risk factors in Japan in 2005. METHODS We first estimated the population attributable fractions (PAFs) of each cancer attributable to known risk factors from relative risks derived primarily from Japanese pooled analyses and large-scale cohort studies and the prevalence of exposure in the period around 1990. Using nationwide vital statistics records and incidence estimates, we then estimated the attributable cancer incidence and mortality in 2005. RESULTS In 2005, ∼55% of cancer among men was attributable to preventable risk factors in Japan. The corresponding figure was lower among women, but preventable risk factors still accounted for nearly 30% of cancer. In men, tobacco smoking had the highest PAF (30% for incidence and 35% for mortality, respectively) followed by infectious agents (23% and 23%). In women, in contrast, infectious agents had the highest PAF (18% and 19% for incidence and mortality, respectively) followed by tobacco smoking (6% and 8%). CONCLUSIONS In Japan, tobacco smoking and infections are major causes of cancer. Further control of these factors will contribute to substantial reductions in cancer incidence and mortality in Japan.BACKGROUND To contribute to evidence-based policy decision making for national cancer control, we conducted a systematic assessment to estimate the current burden of cancer attributable to known preventable risk factors in Japan in 2005. METHODS We first estimated the population attributable fractions (PAFs) of each cancer attributable to known risk factors from relative risks derived primarily from Japanese pooled analyses and large-scale cohort studies and the prevalence of exposure in the period around 1990. Using nationwide vital statistics records and incidence estimates, we then estimated the attributable cancer incidence and mortality in 2005. RESULTS In 2005, ≈ 55% of cancer among men was attributable to preventable risk factors in Japan. The corresponding figure was lower among women, but preventable risk factors still accounted for nearly 30% of cancer. In men, tobacco smoking had the highest PAF (30% for incidence and 35% for mortality, respectively) followed by infectious agents (23% and 23%). In women, in contrast, infectious agents had the highest PAF (18% and 19% for incidence and mortality, respectively) followed by tobacco smoking (6% and 8%). CONCLUSIONS In Japan, tobacco smoking and infections are major causes of cancer. Further control of these factors will contribute to substantial reductions in cancer incidence and mortality in Japan.

Fruit and vegetable consumption and squamous cell carcinoma of the esophagus in Japan: The JPHC study

Epidemiological studies have consistently demonstrated a decrease in the risk of esophageal squamous cell carcinoma (SCC) associated with higher fruit and vegetable intake, although the association has been examined predominantly in case–control studies. Here, we conducted a population‐based prospective cohort study among middle‐aged Japanese men. Lifestyle characteristics were investigated using a self‐administered questionnaire, which included a validated food frequency questionnaire with 138 food and beverage items. We followed a total of 38,790 men aged 45–74 years. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for esophageal SCC, with adjustment for potential confounders. During 297,651 person–years of follow‐up, a total of 116 men were newly diagnosed with esophageal SCC. An increase in consumption of total fruit and vegetables by 100 grams per day (g/day) was associated with an 11% decrease in the incidence of esophageal SCC (95% CI: 1–21%). In particular, a higher intake of cruciferous vegetables was associated with a significant decrease in risk (HR per 100 g/day: 0.44; 95% CI: 0.23–0.82). Stratified analyses revealed that the beneficial effect of fruits and vegetables was not able to completely offset the harmful effect of tobacco and alcohol. Our findings provide further evidence for the protective role of fruits and vegetables in the development of esophageal SCC. To effectively reduce the burden of this disease, however, priority should be placed on smoking and drinking cessation. Finally, cruciferous vegetables deserve further investigation as foods possibly effective in the prevention of esophageal SCC.