Taiki Yamaji

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.

Interaction between Adiponectin and Leptin Influences the Risk of Colorectal Adenoma

Obesity has been associated with an increased risk of colorectal neoplasia, but the mechanisms of this potential association have not been elucidated. We hypothesized that the adipokines adiponectin, leptin, and tumor necrosis factor-alpha (TNF-alpha) may mediate an association between obesity and colorectal cancer. We measured plasma concentrations of total and high-molecular-weight (HMW) adiponectin, leptin, and TNF-alpha in healthy volunteer examinees who underwent total colonoscopy between February 2004 and February 2005, and conducted a case-control study consisting of 778 cases and 735 controls. An inverse association of total and HMW adiponectin was observed with colorectal adenoma (P trend < 0.001 and 0.03, respectively). Further, total adiponectin interacted with leptin, but not TNF-alpha, in relation to colorectal adenoma (P interaction = 0.007). An inverse association of total adiponectin with colorectal adenoma was apparent in the highest two tertiles of leptin, particularly the middle (P trend < 0.001), whereas a positive association of leptin was obvious in the lowest tertile of total adiponectin (P trend = 0.01) after adjusting for potential confounders and body mass index, which is a major determinant of insulin resistance. Adiponectin may exert an anticarcinogenic effect on the large intestine by interfering with leptin, whereas leptin could conversely exert a carcinogenic effect under conditions of a lower abundance of adiponectin. Our findings provide the first epidemiologic evidence for interactive effects of adiponectin and leptin in the early stage of colorectal tumorigenesis, distinct from their involvement in insulin resistance.

Coffee consumption and glucose tolerance status in middle-aged Japanese men.

Aims/hypothesisSeveral studies have reported that coffee has a protective effect against the development of type 2 diabetes. However, few of these studies used the standard glucose tolerance test to diagnose type 2 diabetes. The aim of this study was to investigate the relationship between coffee and green tea consumption and glucose tolerance status as determined using a 75-g OGTT.MethodsWe performed a cross-sectional study of 3224 male officials of the self-defence forces. Glucose tolerance status was determined in accordance with the 1998 World Health Organization criteria, and average intakes of coffee and green tea over the previous year were assessed by a self-administered questionnaire. The figures obtained were adjusted for BMI, physical activity and other factors.ResultsA total of 1130 men were identified as having glucose intolerance (IFG, IGT or type 2 diabetes). Compared with those who did not consume coffee on a daily basis, fasting and 2-h post-load plasma glucose levels were 1.5% and 4.3% lower in those who drank 5 cups of coffee or more per day respectively. The adjusted odds ratios of glucose intolerance for categories of <1, 1–2, 3–4 and ≥5 cups of coffee per day were 1.0 (referent), 0.8 (95% CI 0.6–1.0), 0.7 (95% CI 0.6–0.9) and 0.7 (95% CI 0.5–0.9) respectively (p=0.0001 for trend). No clear association was observed between green tea drinking and glucose tolerance status.Conclusions/interpretationCoffee consumption may inhibit postprandial hyperglycaemia and thereby protect against the development of type 2 diabetes mellitus.

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.

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.

Body weight at age 20 years, subsequent weight change and breast cancer risk defined by estrogen and progesterone receptor status--the Japan public health center-based prospective study.

Few prospective studies have investigated the association between BMI at age 20 years (BMI20y) and breast cancer risk with consideration to estrogen/progesterone receptor status (ER/PR). We evaluated the association between BMI20y and ER/PR‐defined breast cancer risk among 41,594 women in the population‐based Japan Public Health Center‐based Prospective Study. Anthropometric factors were assessed using self‐reported questionnaires. Relative risks (RRs) were estimated by Cox proportional hazards regression models. Through to the end of 2006, 452 breast cancer cases were identified. We observed a statistically significant inverse association between BMI20y and breast cancer incidence [multivariable‐adjusted RR for each 5‐unit increment 0.75 (95%CI = 0.61–0.92)], which was not modified by menopausal or recent BMI status. In contrast, recent BMI and subsequent BMI gain were not associated with increased risk among premenopausal women, but were substantially associated with increased risk among postmenopausal women [corresponding RRrecent BMI = 1.31 (95%CI = 1.07–1.59); RRsubsequent BMI gain = 1.32 (95%CI = 1.09–1.60)]. In subanalyses by receptor status (∼50% of cases), the observed inverse association of BMI20y with risk was consistent with the result for ER–PR– [0.49 (95%CI = 0.27–0.88)], while the observed positive associations of BMI gain with postmenopausal breast cancer risk appeared to be confined to ER+PR+ tumors [corresponding RRfor subsequent BMI gain =2.24 (95%CI = 1.50–3.34)]. Low BMI at age 20 years was substantially associated with an increased risk of breast cancer. In contrast, high recent BMI and subsequent BMI gain from age 20 were associated with increased risk of postmenopausal ER+PR+ tumors.

Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan

BACKGROUND Although case-control studies support the idea that soy foods or isoflavone intake is associated with a decreased risk of lung cancer, little evidence is available from prospective cohort studies. Moreover, no prospective study has addressed this association in men. OBJECTIVE We investigated the association between isoflavone intake and lung cancer incidence. DESIGN We conducted a population-based prospective cohort study in 36,177 men and 40,484 women aged 45-74 y with no history of cancer at baseline in 1995-1999. Participants responded to a validated questionnaire, which included 138 food items. We used Cox proportional hazards regression analysis to estimate the hazard ratios (HRs) and 95% CIs of lung cancer incidence according to isoflavone intake, which was estimated by genistein content from soy foods. RESULTS During 11 y (671,864 person-years) of follow-up, we documented 481 male and 178 female lung cancer cases. In men we found an inverse association between isoflavone intake and risk of lung cancer in never smokers (n = 13,051; multivariate HR in the highest compared with the lowest quartile of isoflavone intake: 0.43; 95% CI: 0.21, 0.90; P for trend = 0.024) but not in current or past smokers. A similar, nonsignificant inverse association was seen in never-smoking women (n = 38,211; HR: 0.67; 95% CI: 0.41, 1.10; P for trend = 0.135). We also tested effect modification by smoking status (P for interaction = 0.085 in men and 0.055 in men and women combined). CONCLUSION In a large-scale, population-based, prospective study in Japan, isoflavone intake was associated with a decreased risk of lung cancer in never smokers.

Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by subsite: Japan Public Health Center–based prospective study†

To date, epidemiologic studies investigating intake of n‐3 and n‐6 polyunsaturated fatty acids and risk of colorectal cancer are limited, and results remain inconsistent. This is the first prospective study to show the association by subsite (proximal colon, distal colon, rectum). To clarify the role of n‐3 and n‐6 polyunsaturated fatty acids intake in colon carcinogenesis, we conducted a large, population‐based prospective study, characterized by high fish consumption and a wide range of n‐3 polyunsaturated fatty acids intakes. Subjects were followed from response to a lifestyle questionnaire in 1995–1999 through 2006. During 827,833 person‐years of follow‐up (average 9.3 years), we identified 1,268 new colorectal cancer cases (521 colon and 253 rectal for men; 350 colon and 144 rectal for women). Compared to the lowest quintile, the relative risk and 95% confidence interval of developing cancer among the fifth quintile of marine n‐3 polyunsaturated fatty acids intake were 0.60 and 0.31–1.14, respectively (p for trend = 0.04) in the colon in women and 0.35 and 0.14–0.88 (p for trend = 0.05) and 1.82 and 0.79–4.20 (p for trend = 0.16) in the proximal and distal colon, respectively, in men. For rectal cancer, the dose response for marine n‐3 polyunsaturated fatty acids s was unclear; rather, we observed U‐shaped associations in men and women. We found no evidence that n‐6 polyunsaturated fatty acids increases or the n‐3/n‐6 ratio decreases the risk of colorectal cancer. Our results suggest that intake of marine n‐3 polyunsaturated fatty acids may be inversely related to the risk of cancer in the proximal site of the large bowel.

Coffee consumption and risk of endometrial cancer : A prospective study in Japan

Coffee has been proposed to decrease the circulating insulin and estrogen levels, which are related to the development of endometrial cancer. However, few studies have prospectively assessed the association between coffee consumption and endometrial cancer. We conducted a population‐based prospective cohort study in 53,724 Japanese women aged 40–69 years with no history of cancer at baseline in 1990–1994. We used Cox proportional hazards regression analysis to estimate the hazard ratio (HR) and 95% confidence interval (CI) of endometrial cancer incidence in relation to coffee consumption. All reported p values are 2‐tailed. During the 15‐year follow‐up period, we documented 117 cases of endometrial cancer. Coffee consumption was significantly associated with a decreased risk of endometrial cancer. After adjustment for age, study area, body mass index, menopausal status, age at menopause for postmenopausal women, parity, use of exogenous female hormones, smoking status and by consumption of green vegetables, beef, pork and green tea, the multivariate HRs (95% CI) of endometrial cancer in women who drank coffee ≤2 days/week, 3–4 days/week, 1–2 cups/day and ≥3 cups/day were 1.00, 0.97 (0.56–1.68), 0.61 (0.39–0.97) and 0.38 (0.16–0.91), respectively (p for trend = 0.007). In contrast, green tea consumption was not significantly associated with a reduced risk of endometrial cancer (p for trend = 0.22). The inverse association between coffee consumption and risk of endometrial cancer was consistently observed in subgroup analyses stratified by potential confounders. Coffee consumption may be associated with a decreased risk of endometrial cancer.

Risk factors for epithelial ovarian cancer in Japan - results from the Japan Public Health Center-based Prospective Study cohort.

The aim of this study was to evaluate the risk factors for invasive primary epithelial ovarian cancer among Japanese women. In 1990-1994, 45,748 women aged 40-69 years were enrolled in the Japan Public Health Center-based Prospective Study cohort. Only 86 epithelial ovarian cancer cases were diagnosed during follow-up through 2008, reflecting the low ovarian cancer incidence rates in Japan. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) according to the exposure of interest. The median age at epithelial ovarian cancer diagnosis was 59 years, with a median follow-up before diagnosis of 7.6 years. There were no statistically significant associations for age at menarche or first birth, breastfeeding, use of exogenous hormones, menopausal status at cohort enrollment, height, body mass index, smoking status, second-hand smoke, alcohol consumption, physical activity and family history of cancer in a first-degree relative. The linear decrease in HR associated with each additional birth was 0.75 (95% CI 0.56-0.99). Among women who usually slept >7 h per day, an HR of 0.4 (95% CI 0.2-0.9) emerged compared to those who slept <6 h. This study did not confirm risk factors for epithelial ovarian cancer among Japanese women that have been reported in studies carried out elsewhere. Usual sleep duration of >7 h per day was inversely associated with epithelial ovarian cancer risk, which is a novel finding that needs to be confirmed in other studies.