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Background Several epidemiological studies have been conducted to draw consistent conclusions regarding the effect of dietary fibre on lung diseases and lung cancer. However, the effect of dietary fibre on the incidence of lung cancer remains unclear in an Asian population. Methods We investigated the association between the intake of total dietary fibre and dietary fibre from different food sources and lung cancer incidence in a Japan public health centre-based prospective study (JPHC). A total of 73 405 participants (33 012 men and 40 393 women) aged 45–74 years were eligible for our study. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a median follow-up of 18.0 years, 1546 (1042 men and 504 women) newly diagnosed cases of lung cancer were ascertained. In the multivariable models, total dietary fibre intake was inversely associated with lung cancer risk in men, the HRs Q5 vs Q1 (95% CI) were 0.77 (0.62 to 0.94), P-trend = 0.020. Dietary fibre intake from vegetables was protectively associated with lung cancer risk in men [HR Q5 vs Q1 (95% CI): 0.80 (0.64 to 0.99), P-trend = 0.053]. However, no such association was observed in women. Conclusions In men, a high intake of total dietary fibre may have preventive benefits for lung cancer incidence: dietary fibre intake from vegetables was associated with a lower incidence of lung cancer. However, similar associations did not appear in women. Further investigations are required to confirm the association between dietary fibre and lung cancer risk in women.

Background The association between body mass index (BMI) and oesophageal cancer (OC) has been consistently negative among Asians, whereas different associations based on histological OC subtypes have been observed in Europeans and North Americans. We examined the association between BMI and OC mortality in the Asia Cohort Consortium. Methods We performed a pooled analysis to evaluate the association between BMI and OC mortality among 842 630 Asians from 18 cohort studies. Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. Results A wide J-shaped association between BMI and overall OC mortality was observed. The OC mortality risk was increased for underweight (BMI Conclusion Extreme obesity and being underweight were associated with an OC mortality risk among Asians. OC mortality and BMI formed a wide J-shaped association mirrored by OSCC mortality. Although the effect of BMI on OSCC and oesophageal adenocarcinoma mortality can be different in Asians, further research based on a large case–control study is recommended.

Background Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. Methods We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. Results In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. Conclusions In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

Background Little is known about the time course of mortality reduction following smoking cessation in Asians who have smoking behaviours distinct from their Western counterparts. We evaluated the level of reduction in all-cause, cardiovascular disease (CVD) and lung cancer mortality by years since quitting smoking, in Asia. Methods Using Cox regression, we analysed individual participant data (n = 709 151) from 16 prospective cohorts conducted in China, Japan, Korea/Singapore, and India/Bangladesh, separately by cohorts. Cohort-specific hazard ratios (HRs) were combined using a random-effects meta-analysis. Results During a mean follow-up of 12.0 years, 108 287 deaths were ascertained—35 658 from CVD and 7546 from lung cancer. Among Asian men, a dose-response relationship of risk reduction in deaths from all causes, CVD and lung cancer was observed with an increase in years after smoking cessation. Compared with never smokers, however, all-cause and CVD mortality among former smokers remained elevated 10–14 years after quitting [multivariable-adjusted HR (95% confidence interval (CI) = 1.25 (1.13–1.37) and 1.20 (1.02–1.41), respectively]. Lung cancer mortality stayed almost 2-fold higher than among never smokers 15–19 years after smoking cessation [1.97 (1.41–2.73)], particularly among former heavy smokers [2.62 (1.71–4.00)]. Women who quitted for ≥5 years retained a significantly elevated mortality from all causes, CVD and lung cancer. Overall patterns of the cessation-mortality associations were similar across countries. Conclusions Our findings suggest that adverse effects of tobacco smoking persist for an extended time period, even for more than two decades, which is beyond the time windows defined in current clinical guidelines for risk assessment of lung cancer and CVD.

BackgroundAlthough many epidemiological studies have reported the preventive effects of soy products and isoflavones on prostate cancer, our previous studies reported that the association between soy and isoflavones and prostate cancer incidence differed according to stage. It is more important to identify modifiable risk factors related to lethal prostate cancer. Here, we investigated the association between soy, soy products and isoflavones intake and prostate cancer mortality, in a prospective study in Japan.MethodsWe conducted a population-based prospective study in 43 580 Japanese men with no history of cancer or cardiovascular disease (aged 45-74 years). Participants completed a validated questionnaire which included 138 food items. We followed participants from 1995 to 2016. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer mortality were calculated according to quintiles of soy products and isoflavones intake, using Cox hazard proportional hazards regression.ResultsDuring 16.9 years follow-up, we registered 221 deaths from prostate cancer. Isoflavones and soy products intake was associated with an increased risk of prostate cancer death, with multivariate HRQ5 vs. Q1=1.39, 95% CI = 0.87-2.20, p for trend = 0.04 for isoflavones and multivariate HRQ5 vs. Q1=1.76, 95% CI = 1.10-2.82, p for trend = 0.04 for soy food.ConclusionsOur study suggested that high intake of soy and isoflavones might increase the risk of prostate cancer mortality.

The main objective of this study was to estimate the cumulative mortality risk for lung cancer according to smoking status and exposure to secondhand smoke (SHS) in Japan. We applied a life-table method to estimate the cumulative risk. Estimated lifetime cumulative risk for 20-year-old non-smokers, former, and current smokers was 3.2%, 7.6%, and 14.9% for men and 1.9%, 5.6%, and 7.2% for women, respectively. For males, the estimated risk was 3.2% for non-smokers not exposed to SHS and 4.1% for non-smokers exposed to SHS. For females, the estimated risk was 1.9% for non-smokers not exposed to SHS and 2.4% for non-smokers exposed to SHS. Lifetime cumulative mortality risk differed greatly according to smoking status. Moreover, SHS exposure resulted in observable differences in lifetime mortality risk. This study may be useful for the development of tailored prevention programs.

Background Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk. Methods Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up. Results Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2–4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5– Conclusions These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.

Background The minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established. We examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease (IHD) risk among a Japanese study population. Methods We surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40–69 y). Seaweed intake in the study subjects was estimated from the food frequency questionnaire at baseline (1990–1994). Stroke and IHD events were identified until the end of 2009 (Cohort I) or 2012 (Cohort II). The hazard ratios (HRs) (95% confidence intervals [CIs]) for incident cardiovascular disease (CVD) and its subtype were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors by sex. Results During 1,493,232 person-years of follow-up, 4,777 strokes and 1,204 IHD cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption were seen in IHD (0.76 [0.58-0.99]; P-trend=0.04) compared to almost no seaweed consumption. Among women, such inverse associations were observed in incident IHD (0.56 [0.36-0.85]; P-trend=0.006). No significant associations were observed between seaweed intake and risk of stroke nor stroke subtypes among either men or women. Conclusions Seaweed intake has been shown to contribute to the prevention of IHD in a large Japanese cohort. Key messages Seaweed intake could be beneficial for prevention of IHD.

Background Optimal cancer survivorship care needs its comprehensive guidelines. We aimed to identify English and Japanese guidelines that include cancer survivorship in their title, the issues highlighted in such guidelines, and any existing oncology practice guidelines in Japan that address these issues. Methods This literature review was performed in three stages. First, guidelines published in English or Japanese that included cancer survivorship in the title were identified. Then, the issues that each cancer survivorship guideline addressed were defined. Lastly, Japanese guidelines that include survivorship issues were sought. Results Six guidelines published in English addressed 31 cancer survivorship issues. No specific cancer survivorship guideline was available in Japanese. Thirty-four Japanese guidelines mentioned cancer survivorship issues. These guidelines addressed screening/surveillance for detecting recurrence or secondary cancer but did not address coordination of care, implications for practice, or inclusion of family. At present, Japanese guidelines poorly address the issue of promotion of a healthy lifestyle in cancer survivors. Also, poorly addressed were long-term and late effects such as pain, psychological distress, fatigue, cognitive dysfunction, cardiovascular effects (including anthracycline-induced cardiac toxicity), sleep disorders, and sexual dysfunction in cancer survivors. Conclusion There is a need for guidelines on optimal coordination of care between oncologists and other health care providers to support patients along the cancer care continuum and specifically to encourage a healthy lifestyle as part of cancer survivorship. The development of a comprehensive Japanese guideline that addresses these issues would help to improve the clinical outcome for cancer survivors in Japan.

Background There is a body of evidence to suggest that cigarette smoking increases the risk of cervical cancer in women, but no study has examined the magnitude of the association in Japanese women. Here, we evaluated the association between cigarette smoking and the risk of cervical cancer in Japanese women based on a systematic review of epidemiological evidence. Methods Original data were obtained from a MEDLINE search using PubMed or from a search of the 'Ichushi' database, as well as by a manual search. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as evaluated previously by the International Agency for Research on Cancer. Meta-analysis of associations was also conducted to obtain a summarized overview of the data. Results We identified two cohort studies and three case-control studies. All five studies had indicated strong positive associations between cigarette smoking and the risk of cervical cancer. Our summary estimate indicated that the relative risk (RR) for individuals who had ever-smoked relative to never-smokers was 2.03 (95% confidence interval: 1.49-2.57). Four studies had also demonstrated dose-response relationships between cigarette smoking and the risk of cervical cancer. Conclusion We conclude that there is convincing evidence that cigarette smoking increases the risk of cervical cancer among Japanese women.

Increasing proportions of smokers in Japan smoke10 cigarettes per day (CPD). Yet, the health risks of low-intensity smoking in Asia are poorly understood.We performed a pooled analysis of 410 294 adults from nine population-based prospective cohort studies participating in the Japan Cohort Consortium. Cigarette-use data were collected at each study baseline in 1983-1994. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were calculated using multivariable-adjusted Cox regression by CPD among current smokers and by age at cessation among former smokers, with never smokers as the referent group. Pooled HRs and CIs were computed using a random-effect model.The smoking prevalence was 54.5% in men and 7.4% in women. About 15.5% of male and 50.4% of female current smokers smoked 1-10 CPD (low-intensity). Both male and female low-intensity smokers had higher all-cause mortality risks than never smokers. Risks were further higher with increasing CPD in a dose-response manner. HRs (95% CIs) were 1.27 (0.97-1.66), 1.45 (1.33-1.59) and 1.49 (1.38-1.62) for 1-2, 3-5 and 6-10 CPD, respectively, in men; 1.28 (1.01-1.62), 1.49 (1.34-1.66) and 1.68 (1.55-1.81) for 1-2, 3-5 and 6-10 CPD, respectively, in women. Similar associations were observed for smoking-related causes of death. Among former low-intensity smokers, younger age at cessation was associated with lower mortality risk.Smoking very low amounts was associated with increased mortality risks in Japan. All smokers should quit, even if they smoke very few CPD.

Background The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored. Methods We examined associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated. Results During an average 12-year follow-up, 23 732 incident lung cancer cases were identified. While BMI was generally associated with a decreased risk, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. After excluding the first five years of follow-up, hazard ratios per 5 kg/m2 increase in BMI were 0.95 (95% CI = 0.90 to 1.00), 0.92 (95% CI = 0.89 to 0.95), and 0.89 (95% CI = 0.86 to 0.91) in never, former, and current smokers, and 0.86 (95% CI = 0.84 to 0.89), 0.94 (95% CI = 0.90 to 0.99), and 1.09 (95% CI = 1.03 to 1.15) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Hazard ratios per 10 cm increase in WC were 1.09 (95% CI = 1.00 to 1.18), 1.12 (95% CI = 1.07 to 1.17), and 1.11 (95% CI = 1.07 to 1.16) in never, former, and current smokers, and 1.06 (95% CI = 1.01 to 1.12), 1.20 (95% CI = 1.12 to 1.29), and 1.13 (95% CI = 1.04 to 1.23) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk (HR = 1.40, 95% CI = 1.26 to 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC. Conclusions The inverse BMI-lung cancer association is not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer.

BACKGROUND: Most previous studies evaluating the association between leisure-time physical activity (LTPA) and risk of death were conducted among generally healthy individuals of European ancestry. We investigated the association of LTPA with all-cause and cause-specific mortality among East Asian populations, including healthy individuals and those with existing chronic diseases, which has been less well characterized. METHODS: We performed pooled analyses among 467 729 East Asian individuals recruited in nine prospective cohorts included in the Asia Cohort Consortium. Cox proportional hazards regressions were used to derive hazard ratios (HRs) and 95% confidence intervals (CIs) associated with LTPA after adjusting for age, sex, education and marital and smoking status. RESULTS: During a mean follow-up period of 13.6 years, 65 858 deaths were identified. Compared with those who reported no or less than 1 h of LTPA per week, an inverse association was observed between the amount of LTPA and all-cause and cause-specific mortality (P for trend < 0.001). The strength of the inverse association was stronger for death due to cardiovascular diseases and causes other than cancer deaths. An inverse association of LTPA with total mortality was observed among individuals with a severe and often life-threatening disease: cancer, stroke or coronary heart disease [hazard ratio (HR) = 0.81, 95% CI = 0.73-0.89 for high vs low LTPA) and those with other chronic diseases such as diabetes or hypertension (HR = 0.86, 95% CI = 0.80-0.93 for high vs low LTPA). No clear modifying effects by sex, body mass index or smoking status were identified. CONCLUSIONS: Regular participation in LTPA is associated with reduced mortality in middle-aged and elder Asians regardless pre-existing health conditions.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P

Lifetime cumulative incidence and mortality risk for gastric cancer was estimated by risk classifications, which will be useful for designing individually tailored prevention strategy., Objective To estimate cumulative incidence and mortality risk for gastric cancer by risk category. Methods Risk was classified into four types according to the presence/absence of Helicobacter pylori infection and chronic atrophic gastritis: in order of lowest to highest risk, Group A: H. pylori(−) and atrophic gastritis(−); Group B: H. pylori(+) and atrophic gastritis(−); Group C:H. pylori(+) and atrophic gastritis(+); and, Group D: H. pylori(−) and atrophic gastritis(+). We used vital statistics for the crude all-cause and crude gastric cancer mortality rates in 2011 and data from population-based cancer registries (the Monitoring of Cancer Incidence in Japan) for gastric cancer incidence in 2011. For relative risk and prevalence, we used the results of a meta-analysis integrating previous studies and data from the Japan Public Health Center-based Prospective Study for the Next Generation, respectively (baseline survey 2011–16). We calculated the crude incidence and mortality rates and estimated the cumulative risk using a life-table method. Results The estimated lifetime cumulative incidence risk was 11.4% for men and 5.7% for women. The estimated risk for Groups A, B, C and D was 2.4%, 10.8%, 26.7% and 35.5% for men, and 1.2%, 5.5%, 13.5% and 18.0% for women, respectively. Similarly, the estimated lifetime cumulative mortality risk was 3.9% for men and 1.8% for women. The estimated risk of mortality for Groups A, B, C and D was 0.8%, 3.6%, 9.0% and 12.0% for men, and 0.4%, 1.7%, 4.2% and 5.7% for women, respectively. Conclusions Our results may be useful for designing individually tailored prevention programs.

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

OBJECTIVE Although cigarette smoking is a well-established risk factor for head and neck cancer, the impact of smoking on head and neck cancer might vary among geographic areas. To date, however, no systematic review of cigarette smoking and head and neck cancer in the Japanese population has yet appeared. METHODS We conducted a systematic review of previous epidemiological studies for cigarette smoking and head and neck cancer among Japanese. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. A meta-analysis was conducted to obtain summary estimates for the overall magnitude of association. RESULTS We identified five cohort studies and 12 case-control studies. Four of five cohort studies and 11 of 12 case-control studies showed a strong positive association between cigarette smoking and head and neck cancer. Nine of 12 studies indicated a dose-response relationship between cigarette smoking and the risk of head and neck cancer. Meta-analysis of 12 studies indicated that the summary relative risk for ever smokers relative to never smokers was 2.43 (95% confidence interval: 2.09-2.83). Summary relative risks for current and former smokers relative to never smokers were 2.68 (2.08-3.44) and 1.49 (1.05-2.11), respectively. CONCLUSIONS Cigarette smoking is a convincing risk factor for head and neck cancer in the Japanese population.

Aims Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. Methods and results The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000–04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50–79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality. The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73–1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55–0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64–0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01–4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07–11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03–1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40–0.99), respectively. Conclusion An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Increasing evidence implicates human cytomegalovirus (HCMV) in the etiopathogenesis of breast cancer. Antibodies to this virus in patients with breast cancer have been reported, but no large-scale studies have been conducted to determine whether the antibody levels differ between patients and matched controls. Using specimens from a large (1712 subjects) multiethnic case-control study, we aimed to determine whether the levels of antibodies to the HCMV glycoprotein B (gB) differed between patients and controls and whether they were associated with particular immunoglobulin γ marker (GM), κ marker (KM), and Fcγ receptor (FcγR) genotypes. A combined analysis showed that anti-gB immunoglobulin G antibody levels were higher in healthy controls than in patients (P < .0001). Stratified analyses showed population-specific differences in the magnitude of anti-gB antibody responsiveness and in the contribution of particular GM, KM, and FcγR genotypes to these responses. These findings may have implications for HCMV-based immunotherapy against breast cancer and other HCMV-associated diseases.

The association between alcohol consumption, genetic polymorphisms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) and gastric cancer risk is not completely understood. We investigated the association between ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms, alcohol consumption and the risk of gastric cancer among Japanese subjects in a population-based, nested, case-control study (1990-2004). Among 36 745 subjects who answered the baseline questionnaire and provided blood samples, 457 new gastric cancer cases matched to 457 controls were used in the analysis. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using logistic regression models. No association was observed between alcohol consumption, ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms and gastric cancer risk. However, considering gene-environmental interaction, ADH1C G allele carriers who drink ≥150 g/week of ethanol had a 2.5-fold increased risk of gastric cancer (OR = 2.54, 95% CI = 1.05-6.17) relative to AA genotype carriers who drink 0 to

Background : Non-participants to psychosocial studies have been shown to have higher mortality, and mortality differs between partial and complete responders to psychosocial questionnaires. Yet, there is very little information available directly linking survey response status with completing suicide. Methods : The study population consisted of the participants of the Japanese Public Health Center-based prospective study. Ninety-nine thousand four hundred thirty-nine subjects who returned the 10-year follow-up questionnaire and 31 754 individuals who did not return the questionnaire were included in our analyses. The risk of dying by suicide according to response status was estimated by Cox regression models. Results : There were 358 suicides during 1 128 831 person-years of follow-up (mean follow-up time: 8.6 years). Of those who returned the questionnaire, 53.9% were full responders, 42.8% were partial non-responders, and 3.3% were complete non-responders. The risk of suicide was increased for both complete non-responders [hazard ratio (HR) = 1.84, 95% confidence interval (CI), 0.51, 6.64] and partial non-responders (HR = 1.36, 95% CI, 0.999, 1.84) to the questionnaire as a whole. The adjusting variables explained around 40% of the risk for complete non-responders whereas they did not explain the increased risk of suicide for partial non-responders. The risk of dying by suicide was significantly increased for partial non-responders to the subscale on coping (HR = 1.36, 95% CI, 1.01, 1.85) and for complete non-responders to questions on sleep (HR = 2.07, 95% CI, 1.03, 4.16). Conclusions : Partial and complete non-responders have increased suicide risk compared with complete non-responders. More than one non-responder category should therefore be considered when interpreting data pertaining to psychosocial questionnaires in longitudinal studies.

A thyroid ultrasound examination programme has been conducted in Fukushima Prefecture, Japan, after the nuclear disaster in 2011. Although remarkably high prevalence of thyroid cancer was observed, no relevant quantitative evaluation was conducted. We calculated the observed/expected (O/E) ratio of thyroid cancer prevalence for the residents aged ≤20 years. Observed prevalence was the number of thyroid cancer cases detected by the programme through the end of April 2015. Expected prevalence was calculated as cumulative incidence by a life-table method using the national estimates of thyroid cancer incidence rate in 2001-10 (prior to the disaster) and the population of Fukushima Prefecture. The underlying assumption was that there was neither nuclear accident nor screening intervention. The observed and estimated prevalence of thyroid cancer among residents aged ≤20 years was 160.1 and 5.2, respectively, giving an O/E ratio of 30.8 [95% confidence interval (CI): 26.2, 35.9]. When the recent increasing trend in thyroid cancer was considered, the overall O/E ratio was 22.2 (95% CI: 18.9, 25.9). The cumulative number of thyroid cancer deaths in Fukushima Prefecture, estimated with the same method (annual average in 2009-13), was 0.6 under age 40. Combined with the existing knowledge about radiation effect on thyroid cancer, our descriptive analysis suggests the possibility of overdiagnosis. Evaluation including individual-level analysis is required to further clarify the contribution of underlying factors.

Summary Cyclin B1 is a checkpoint protein that regulates cell division from G2 to the M phase. Studies in mice have shown that cyclin B1 vaccine-induced immunity significantly delayed or prevented the spontaneous cancer development later in life. We hypothesized that if these results showing a protective effect of anti-cyclin B1 antibodies could be extrapolated to the human condition, cancer-free individuals should have higher levels of endogenous antibodies than patients with cancers characterized by the over-expression of this tumour-associated antigen. To test this hypothesis, we characterized a large (1739 subjects) number of multi-ethnic patients with breast cancer (which over-expresses cyclin B1) and matched controls for anti-cyclin B1 immunoglobulin (Ig)G antibodies. Multivariate analyses, after adjusting for the covariates, showed that cancer-free individuals had significantly higher levels of naturally occurring IgG antibodies to cyclin B1 than patients with breast cancer (mean ± standard deviation: 148·0 ± 73·6 versus 126·1 ± 67·8 arbitrary units per ml; P < 0·0001). These findings may have important implications for cyclin B1-based immunotherapy against breast cancer and many other cyclin B1-over-expressing malignancies.

With increased interest in non-alcoholic steatohepatitis, its common co-morbid condition, obesity, has recently attracted much attention as a risk factor for liver cancer. Recent studies also suggest that obesity may play a role in the development of liver cancer in alcoholic cirrhosis or viral hepatitis and in the general population.We systematically reviewed epidemiologic studies on overweight/obesity and liver cancer among Japanese populations. Original data were obtained by searching the MEDLINE (PubMed) and Ichushi databases, complemented by manual searches. The evaluation was performed in terms of the magnitude of association in each study and the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient'), together with biologic plausibility.Among nine cohort studies identified, five (four on patients with chronic liver disease and one on local residents) reported a weak to strong positive association, while four (one on patients with hepatitis B and three on local residents) found no association [summary relative risk for one unit increase in body mass index (kg/m(2)) 1.07, 95% confidence interval 1.03-1.10]. All three case-control studies identified (two on cirrhotic patients and one on atomic bomb survivors) reported a strong positive association (summary relative risk 1.31, 95% confidence interval 1.12-1.53). Overall, the summary relative risk was estimated at 1.13 (95% confidence interval 1.07-1.20), and overweight/obese individuals had a relative risk of 1.74 (95% confidence interval 1.33-2.28) compared with those who had normal/low weight.We conclude that overweight or obesity 'probably' increases the risk of primary liver cancer, to a moderate degree, among the Japanese population.

The anticarcinogenic potential of vitamin D might be mediated by not only calcium metabolism but also other mechanisms initiated by vitamin D receptor (VDR). The authors measured plasma 25-hydroxyvitamin D in healthy volunteer examinees who underwent total colonoscopy in Tokyo, Japan, 2004-2005, and evaluated its influence on colorectal adenoma, both alone and in interaction with VDR polymorphisms, which correspond to the FokI and TaqI restriction sites. The main analysis of plasma 25-hydroxyvitamin D included 737 cases and 703 controls. Compared with the lowest quintile of plasma 25-hydroxyvitamin D, only the highest was related to a significantly decreased odds ratio of colorectal adenoma (odds ratio = 0.64, 95% confidence interval: 0.45, 0.92). In contrast, all but the lowest quintile of dietary calcium intake presented similarly reduced odds ratios (odds ratio for the highest = 0.67, 95% confidence interval: 0.47, 0.95). Of note, the association between plasma 25-hydroxyvitamin D levels and colorectal adenoma was modified by the TaqI polymorphism of the VDR gene (P(interaction) = 0.03) but not by dietary calcium intake (P(interaction) = 0.93). These observations highlight the importance of vitamin D in colorectal tumorigenesis. Vitamin D might protect against colorectal neoplasia, mainly through mechanisms other than the indirect mechanism via calcium metabolism.

Objective: Higher levels of physical activity have been consistently associated with a decreased risk of colon cancer, but not rectal cancer, in Western populations. The present study systematically evaluated epidemiologic evidence on the association between physical activity and colorectal cancer risk among the Japanese population. Methods: Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented by manual searches. The associations were evaluated based on the strength of evidence, the magnitude of association and biologic plausibility. Results: Two cohort studies and six case –c ontrol studies were identified. A weak to strong protective association between physical activity and colon cancer risk was observed in both cohort studies, showing a graded relationship, and among the majority of case –c ontrol studies, with some showing a dose–response relationship. The association observed in cohort studies was more consistent and stronger in men than in women and for proximal colon cancer than for distal colon cancer. A protective association with rectal cancer was found only in case–control studies, but the evidence was less consistent and weaker than that observed for colon cancer. Conclusions: Physical activity probably decreases the risk of colorectal cancer among the Japanese population. More specifically, the evidence for the colon is probable, whereas that for the rectum is insufficient.

Previous studies have reported the existence of an association between brain-derived neurotrophic factor and major depression. However, the possible role of brain-derived neurotrophic factor in the pathophysiology of major depression after cancer diagnosis has not yet been investigated. Subjects were collected using the Lung Cancer Database project. Using the cut-off scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), 81 subjects with depression (HADS-D > 10) and 81 subjects without depression (HADS-D < 5) were selected. The two groups were matched for age, sex, clinical stage and performance status. The serum brain-derived neurotrophic factor levels were measured using an enzyme-linked immunosorbent assay method. The serum brain-derived neurotrophic factor levels were not statistically different between the subjects in the depression group [29.1 (13.6) ng/ml; mean (SD)] and the non-depression group [31.4 (10.6) ng/ml] (P = 0.22). In a stratified analysis by gender, however, the mean serum brain-derived neurotrophic factor level in the depression group tended to be lower than that in the non-depression group among women (n = 24 pairs, P = 0.06). Major depression after cancer diagnosis is not associated with serum brain-derived neurotrophic factor levels.

Although alcohol drinking is considered as an important risk factor for esophageal cancer, the magnitude of the association might be varied among geographic areas. Therefore, we reviewed epidemiologic studies on the association between alcohol drinking and esophageal cancer among the Japanese population. Original data were obtained from MEDLINE, searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. We identified four cohort studies and nine case-control studies. All cohort studies and case-control studies showed strong positive associations between esophageal cancer and alcohol drinking. All cohort studies and six case-control studies showed that alcohol drinking had the dose- or frequency-response relationships with esophageal cancer. In addition, four case-control studies showed that acetaldehyde dehydrogenase Glu504Lys polymorphism had strong effect modification with alcohol drinking. We conclude that there is convincing evidence that alcohol drinking increases the risk of esophageal cancer in the Japanese population.

Objective: Clinical trials of b-carotene supplementation and recent large-scale prospective studies have called into question the protective effects of vegetable and fruit consumption against lung cancer. To re-assess this issue, we reviewed data from Japanese epidemiological studies. Methods: Original data were obtained from searches of MEDLINE and the Japana Centra Revuo Medicina (Ichushi) database. The associations were assessed based on their magnitude and the strength of the evidence, together with their biological plausibility as previously evaluated by the International Agency for Research on Cancer. Results: We identified six cohort studies and four case–control studies on the consumption of vegetables and/or fruit. We focused on fruit and green-yellow vegetables as food items, as they were included in more of the studies, and insufficient data were available on other types of vegetables. Among the three cohort and two case–control studies that reported on greenyellow vegetables, only one of each study type showed a weak inverse association between lung cancer risk and their consumption. Two of the four cohort studies and one (or possibly two) of the four case–control studies demonstrated a weak inverse correlation between lung cancer risk and fruit consumption. Meta-analysis for fruit consumption revealed a summary relative risk that was significantly smaller than unity. Conclusions: Our analysis of the Japanese epidemiological data showed that fruit consumption possibly decreased the risk of lung cancer, but found insufficient evidence of a link with vegetable consumption. Further prospective studies should assess the effects of consuming these food groups.

Objective: Male smoking prevalence is still high in Japan, and quantitative information for tobacco control is scarce. The aim of the present study was to project cancer mortality among Japanese males under different future scenarios of smoking prevalence. Methods: The target population comprised Japanese males aged 40–79 years in 2007, whose smoking prevalence was 35%. On the basis of the pooled data from three large-scale cohort studies in Japan, the effects of age, years of smoking and years after smoking cessation on the time to all-cancer or lung cancer death were estimated by an accelerated failure time model. The parameter estimates were used to project the annual number of deaths from all cancers and lung cancer by running simulations for different future scenarios of smoking prevalence. Each scenario was evaluated by the cumulative number of avoided deaths when compared with the status quo and by the percent change (from the baseline year) in agestandardized rate of mortality. Results: Reducing the smoking prevalence from 35% in 2007 to 0% in 2017 was estimated to avoid 333 900 all-cancer deaths and 171 100 lung cancer deaths in 20 years. Even when we shortened the projection period to 10 years, these numbers of avoided deaths would be 81 100 and 38 800, respectively. The age-standardized rate of all-cancer mortality was estimated to decrease by 9.6% in 10 years and 18.1% in 20 years. Conclusions: Reducing the prevalence of smoking among males would be effective in reducing the cancer burden even within 10 years in countries with a high male smoking prevalence.

Gastric carcinogenesis may be under the combined influence of factors related to the host, Helicobacter pylori bacterial virulence and the environment. One possible host-related factor is the inflammatory or immune response. To clarify this point, we investigated the association between plasma levels of C-reactive protein (CRP) and serum amyloid A (SAA) and the subsequent risk of gastric cancer in a population-based nested case-control study. Subjects were observed from 1990 to 2004. Among 36 745 subjects who answered the baseline questionnaire and provided blood samples, 494 gastric cancer cases were identified and matched to 494 controls for our analysis. The overall distribution of CRP and SAA was not apparently associated with the development of gastric cancer. However, a statistically significant increased risk was observed when subjects were categorized dichotomously. The adjusted odds ratio (OR) for the development of gastric cancer for the CRP-positive group (CRP > 0.18 mg/dl) compared with the CRP-negative group was 1.90 [95% confidence interval (CI): 1.19-3.02, P = 0.007]. The OR for the SAA-positive group (SAA > 8 mug/ml) compared with the SAA-negative group was 1.93 (95% CI: 1.22-3.07, P = 0.005). In conclusion, our results suggest that those who react strongly to inflammation or who have a high host immune response, as reflected by extremely elevated plasma levels of CRP and SAA, are at a high risk to develop gastric cancer.

A base excision repair enzyme, NTH1, has activity that is capable of removing oxidized pyrimidines, such as thymine glycol (Tg), from DNA. To clarify whether the NTH1 gene is involved in gastric carcinogenesis, we first examined the NTH1 expression level in eight gastric cancer cell lines, and the results showed that NTH1 expression was downregulated in all of them, including cell line AGS. Next, a comparison of excisional repair activity against Tg by empty vector-transfected AGS clones and FLAG-NTH1-expressing AGS clones showed that a low NTH1 expression level led to low capacity to repair the damaged base in the gastric epithelial cells. Reduced messenger RNA expression of NTH1 was also detected in 36% (18/50) of primary gastric cancers. Moreover, immunohistochemical analysis revealed that NTH1 was predominantly localized in the cytoplasm in 24% (12/50) of the primary gastric cancers in contrast to the nuclear localization in non-cancerous tissue, suggesting impaired excisional repair ability for nuclear DNA. No associations between clinicopathological factors and NTH1 expression level or localization pattern were detected in the gastric cancers. Next, we found two novel genetic polymorphisms, i.e. c.-163C>G and c.-241_-221del, in the NTH1 promoter region, and a luciferase assay showed that both were associated with reduced promoter activity. However, there were no associations between the polymorphisms and risk of gastric cancer in a gastric cancer case-control study. These findings suggested that downregulation of NTH1 expression and abnormal localization of NTH1 may be involved in the pathogenesis of a subset of gastric cancers.

Background Little is known about the influence of blood pressure (BP) on cardiovascular disease (CVD) outcomes among Asian populations. Methods We examined population attributable fractions (PAFs) and hazard ratios (HRs) associated with BP in relation to stroke and coronary heart disease (CHD) incident and mortality within a cohort of 33,372 Japanese men and women aged 40-69 years, free of prior diagnosis of cancer and CVD. The BP was classified based on modified criteria of the 2003 European Society of Hypertension-European Society of Cardiology guidelines. A total of 943 stroke events, 182 CHD events, 262 stroke deaths, and 120 CHD deaths occurred between the baseline questionnaire (1990-1994) and the end of follow-up in 31 December 2003. Results BP levels were linearly associated with incidence and mortality of CVD in men and women. According to the PAF estimation, the elimination of normal to severe hypertension would prevent 64% of stroke incidence in men and 50% in women; 67% of stroke mortality in men and 29% in women; and 38% of total CVD mortality in men and 36% in women. The PAF estimate for total stroke incidence was the highest for mild hypertension, and lower for moderate to severe hypertension in both sexes. Conclusions The contributions of normal BP, high normal BP, and mild hypertension to the occurrence of stroke events were greater than those made by moderate and severe hypertension, highlighting the importance of primary prevention and of treatment for low-to-moderate degrees of hypertension.

Background: Although alcohol consumption has been recognized as a risk factor for primaryliver cancer, it will be informative to summarize relevant epidemiologic data in the Japanesewho have characteristic environmental determinants (e.g. hepatitis C virus infection) andgenetic traits (e.g. presence of poor acetaldehyde metabolizers).Methods: We systematically reviewed epidemiologic studies on alcohol drinking and livercancer among Japanese populations. Original data were obtained through searches of theMEDLINE (PubMed) and Ichushi databases, complemented with manual searches. Theevaluation was performed in terms of the magnitude of association (‘strong’, ‘moderate’,‘weak’ or ‘no association’) in each study and the strength of evidence (‘convincing’, ‘probable’,‘possible’ or ‘insufficient’), together with biological plausibility as previously assessed by theInternational Agency for Research on Cancer.Results: Among 22 cohort studies identified, 14 (64%) reported weak to strong positiveassociations between alcohol and liver cancer risk, 3 (14%) reported no association and five(23%) reported weak to moderate inverse associations; such inverse associations were foundmostly in follow-up studies of patients with chronic liver disease (particularly, cirrhoticpatients), yet recent studies on patients with chronic hepatitis C presented fairly consistentpositive associations. Of 24 case–control studies identified, 19 (79%) showed weak to strongpositive associations, whereas the remainder demonstrated no association (n ¼ 4) or a mod-erate inverse association (n ¼ 1).Conclusion: We conclude that there is ‘convincing’ evidence that alcohol drinking increasesthe risk of primary liver cancer among the Japanese population.Keywords: systematic review – epidemiology – alcohol – liver cancer – Japanese

Background: Although lower education has been associated with poorer health, few studies have examined whether lower education affects mortality, incidence, both or neither of cancer and cardiovascular disease. Methods: The authors conducted a population-based prospective cohort study among 39 228 men and women who were aged 40–59 years and lived in four areas in Japan. Information on education and lifestyle variables were obtained by a self-administered questionnaire in 1990. Follow-up until the end of 2002 (for incidence) or 2003 (for mortality) ascertained 2573 and 1251 incident cases of cancer and cardiovascular disease, respectively, and 2430 deaths (1064 from cancer, 548 from cardiovascular disease and 818 from other causes). Results: After adjustment for demographic and lifestyle variables, 12 years of education, was associated with significantly higher mortality from all causes [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 1.05–1.42] and cardiovascular disease (HR = 1.44, 95% CI: 1.01–2.06), but was not associated with higher incidence of cardiovascular disease (HR = 0.96, 95% CI: 0.78–1.18) or higher mortality or incidence of cancer. Conclusion: The findings suggest that lower education is associated with higher mortality from all causes and cardiovascular disease among the Japanese population that is not totally attributable to lifestyle differences or higher cardiovascular disease incidence.

Although numerous studies of type A behaviour and risk of coronary heart disease (CHD) have been reported in the west (with mixed findings), few studies have been carried out in Asian populations.We examined prospectively the association between type A-behaviour and risk of CHD incidence within a cohort of 86 361 Japanese men and women aged 40-69 years. A total of 669 cases of newly diagnosed CHD occurred between the baseline questionnaire (1990-94) and the end of follow-up in January 2004.We found no overall evidence of an association between type A and CHD incidence. The multivariate hazard ratio (HR) and 95% confidence intervals for CHD incidence in the highest vs lowest level of type A was 1.19 (0.94-1.51) overall. Contrary to expectation, Japanese men with lower levels of type A behaviour (lower levels of impatience, aggressiveness and competitiveness) appeared to be at significantly increased risk of CHD incidence (HR = 1.32; 95% CI 1.02-1.72). In contrast to men, there was insignificant but a tendency for reduced risk of CHD incidence (HR = 0.79, 95% CI 0.46-1.34) for women with lower levels of type A behaviour.Type A behaviour does not predict CHD incidence in the Japanese population. Among males, type B behavioural patterns appear to confer increased CHD risk. Our findings suggest that the cardio-toxic effect of type A behaviour is gender-specific and culturally contingent.

The impact of total physical activity level on cancer risk has not been fully clarified, particularly in non-Western, relatively lean populations. The authors prospectively examined the association between daily total physical activity (using a metabolic equivalents/day score) and subsequent cancer risk in the Japan Public Health Center-based Prospective Study. A total of 79,771 general-population Japanese men and women aged 45-74 years who responded to a questionnaire in 1995-1999 were followed for total cancer incidence (4,334 cases) through 2004. Compared with subjects in the lowest quartile, increased daily physical activity was associated with a significantly decreased risk of cancer in both sexes. In men, hazard ratios for the second, third, and highest quartiles were 1.00 (95% confidence interval (CI): 0.90, 1.11), 0.96 (95% CI: 0.86, 1.07), and 0.87 (95% CI: 0.78, 0.96), respectively (p for trend = 0.005); in women, hazard ratios were 0.93 (95% CI: 0.82, 1.05), 0.84 (95% CI: 0.73, 0.96), and 0.84 (95% CI: 0.73, 0.97), respectively (p for trend = 0.007). The decreased risk was more clearly observed in women than in men, especially among the elderly and those who regularly engaged in leisure-time sports or physical exercise. By site, decreased risks were observed for cancers of the colon, liver, and pancreas in men and for cancer of the stomach in women. Increased daily physical activity may be beneficial in preventing cancer in a relatively lean population.

Few studies have investigated the effects of fruit and vegetables on the risk of both cancer and cardiovascular disease (CVD). The authors examined associations between fruit and vegetable consumption and risk of total cancer and CVD in the same Japanese population. During 1995-1998, a validated food frequency questionnaire was administered in nine areas to 77,891 men and women aged 45-74 years. During as many as 459,320 person-years of follow-up until the end of 2002, 3,230 cancer cases and 1,386 CVD cases were identified. Higher consumption of fruit, but not vegetables, was associated with significantly lower risk of CVD: multivariate hazard ratios for the highest versus lowest quartiles of intake were 0.81 (95% confidence interval (CI): 0.67, 0.97; trend p = 0.01) for fruit and 0.97 (95% CI: 0.82, 1.15; trend p = 0.66) for vegetables. Consumption of fruit or vegetables was not associated with decreased risk of total cancer: corresponding hazard ratios were 1.02 (95% CI: 0.90, 1.14; trend p = 0.95) for fruit and 0.94 (95% CI: 0.84, 1.05; trend p = 0.16) for vegetables. This prospective cohort study demonstrated that, in the Japanese population, consumption of fruit is associated with lower risk of CVD, whereas fruit or vegetables may not be associated with lower risk of total cancer.

The incidence of prostate cancer is much lower in Asian than Western populations. Given that environmental factors such as dietary habits may play a major role in the causation of prostate cancer and the high consumption of green tea in Asian populations, this low incidence may be partly due to the effects of green tea. The JPHC Study (Japan Public Health Center-based Prospective Study) was established in 1990 for cohort I and in 1993 for cohort II. The subjects were 49,920 men aged 40-69 years who completed a questionnaire that included their green tea consumption habit at baseline and were followed until the end of 2004. During this time, 404 men were newly diagnosed with prostate cancer, of whom 114 had advanced cases, 271 were localized, and 19 were of an undetermined stage. Green tea was not associated with localized prostate cancer. However, consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer. The multivariate relative risk was 0.52 (95% confidence interval: 0.28, 0.96) for men drinking 5 or more cups/day compared with less than 1 cup/day (p(trend) = 0.01). Green tea may be associated with a decreased risk of advanced prostate cancer.

Background: The relationship between alcohol consumption and risk of lung cancer is controversial. Based on a systematic review of epidemiologic evidence, we evaluated this association among the Japanese population, who may be more susceptible to alcohol-related diseases than Western populations. Methods: Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. Results: We identified seven cohort studies and two case-control studies. One cohort study demonstrated a strong positive association between alcohol drinking and the risk of female lung cancer, but the association almost disappeared after adjustment for smoking. The other eight studies showed a weak positive or no association. Although smoking is the bestestablished risk factor for lung cancer, only five cohort studies presented smoking-adjusted risks out of all nine identified. Furthermore, only two studies explicitly reported the risk estimate for ex-drinkers who may have quit alcohol drinking after the development or diagnosis of the disease and have an apparently higher risk. Conclusion: We conclude that the epidemiologic evidence on the association between alcohol drinking and lung cancer risk remains insufficient in terms of both the number and methodological quality of studies among the Japanese population.

We evaluated the association between tobacco smoking and gastric cancer risk among the Japanese population based on a systematic review of epidemiologic evidence.Original data were collected by searches of MEDLINE using PubMed, complemented with manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility, as evaluated previously by the International Agency for Research on Cancer.Ten cohort studies and 16 case-control studies were identified. In men, most studies reported moderate or strong positive associations between smoking and gastric cancer. In women, the positive association was weaker than in men. Of eight studies (three cohort studies and five case-case control studies), two cohort and three case control studies reported a weakly to strongly increased risk of gastric cancer. The summary relative risk for current smokers was estimated to be 1.56 (95% confidence intervals 1.36-1.80), 1.79 (1.51-2.12), 1.22 (1.07-1.38) for the total population, men and women, respectively.We conclude that there is convincing evidence that tobacco smoking moderately increases the risk of gastric cancer among the Japanese population.

Background Although tobacco smoking is the best established risk factor for lung cancer, the association is not as strong among Japanese as among Western populations. It would be of value, therefore, to quantify that association in Japan based on a systematic review of epidemiological evidence for the primary prevention of lung cancer. Methods Original data were obtained from MEDLINE searches using PubMed, supplemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of the association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. A meta-analysis was also conducted to estimate the summary measure of those associations. Results A total of 8 cohort studies and 14 case-control studies were identified, almost all of which consistently showed a strong association of current smoking with the risk of lung cancer. The summary relative risk for current smokers versus never smokers was estimated as 4.39 (95% confidence interval 3.92-4.92) for men and 2.79 (95% confidence interval 2.44-3.20) for women. Cohort studies and case-control studies gave reasonably consistent summary measures. The summary relative risks were 11.7 and 2.30 for squamous cell carcinoma and adenocarcinoma, respectively, in men, and were 11.3 and 1.37 correspondingly in women. Conclusion There is convincing evidence that tobacco smoking strongly increases the risk of lung cancer in the Japanese population, with the relative risk for current smokers compared with never smokers measuring around 4.4 for men and 2.8 for women.

Background: The lung cancer database project was established in 1999 at the National Cancer Center Hospital East, Japan, as an ongoing project to integrate data on various factors in lung cancer patients. The aim of the project was to construct a large-scale cancer registry for lung cancer that would contribute to basic research and clinical research in the future. Methods:BetweenJuly1999andJuly2004,consecutivelungcancerpatientswererecruitedinto this project. The baseline survey consisted of self-administered questionnaires concerning variousdemographicdata,healthhabitsandpsychologicalfactors.Medicalinformationwasobtained from the patients’ medical charts. Urine specimens and blood samples were collected, and DNA was extracted from blood lymphocytes. Results:Outofthe2506patientswhowereaskedtoparticipateintheproject,2036(81%)patients with newly diagnosed, untreated primary lung cancer were enrolled. The final analytic cohort consisted of 1995 patients. Virtually all of the 1995 patients (corresponding rate, 99%) completed the questionnaires on demographic data and health habits. The corresponding rates for the questionnaires on psychological factors and dietary habits were 99 and 94%, respectively. In a follow-up survey conducted to determine vital status as of December 2004, a total of 1051 patients (53%) had died and 44 patients (2%) were lost to follow-up. Conclusions: This paper overviews the rationale for initiating the lung cancer database project, Japan. This database should prove useful for researchers examining the pathogenesis of lung cancer and may contribute to the formulation of a framework for cancer treatment.

BACKGROUND: Endometriosis, an estrogen-dependent disease, is believed to be influenced by multiple genetic and environmental factors. Here, we evaluated whether the risk and severity of endometriosis are associated with polymorphisms in estradiol-synthesizing enzyme genes: the Ser312Gly polymorphism in 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and the Arg264Cys polymorphism in cytochrome P450, subfamily XIX (CYP19). METHODS: All participants underwent diagnostic laparoscopy, and the stage of endometriosis was determined according to the Revised American Fertility Society classification. Of the 138 women enrolled, 59 had no endometriosis, 21 had stage I, 10 had stage II, 23 had stage III and 25 had stage IV. SNPs were discriminated by allele-specific oligonucleotide hybridization. RESULTS: Individuals having at least one A-allele (A/G or A/A genotype) of HSD17B1 showed a significantly increased risk of endometriosis (A/G genotype: adjusted OR, 3.06; 95%CI 1.21-7.74; A/A genotype: adjusted OR, 3.02; 95%CI 1.08-8.43). There was a significant trend associating A/G + A/A genotypes with severity of endometriosis (P for trend < 0.01). No statistically significant association was found for the CYP19 polymorphism. CONCLUSIONS: Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis.

Background: An association between coffee drinking and reduced risk of liver cancer has been suggested by animal studies, but epidemiologic evidence of such an association in a high-risk population is lacking. We conducted a large-scale population-based cohort study of the association between coffee drinking and hepatocellular carcinoma (HCC) in a Japanese population. Methods: Newly diagnosed case patients (250 men and 84 women) with HCC were identified from a 10-year follow-up of the Japan Public Health Center-based Prospective Study, which consists of 90,452 middle-aged and elderly Japanese subjects (43,109 men and 47,343 women). Case patients were grouped according to coffee intake and were stratified by hepatitis virus infection, sex, age, diet, lifestyle factors, and previous history of liver disease. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for HCC were calculated with Cox proportional-hazards modeling. All statistical tests were two-sided. Results: Subjects (men and women combined) who consumed coffee on a daily or almost daily basis had a lower HCC risk than those who almost never drank coffee (HR = 0.49 [95% CI = 0.36 to 0.66]); risk decreased with the amount of coffee consumed (compared with nondrinkers, the HR for 1-2 cups per day = 0.52 [95% CI = 0.38 to 0.73]; for 3-4 cups per day = 0.48 [95% CI = 0.28 to 0.83]; for > or =5 cups per day = 0.24 [95% CI = 0.08 to 0.77], P(trend) < .001). The risk of liver cancer in almost never drinkers in this population was 547.2 cases per 100,000 people over 10 years, but it was 214.6 cases per 100 000 people with drinking coffee on a daily basis. The inverse association persisted when the participants were stratified by lifestyle factors. Similar associations were observed when the analysis was restricted to hepatitis C virus-positive patients (all daily drinkers compared with nondrinkers: HR =0.57 [95% CI = 0.37 to 0.86]), to hepatitis B virus-positive patients (HR = 0.60 [95% CI = 0.31 to 1.18]) and to subjects with no past history of chronic liver disease (HR = 0.45 [95% CI = 0.30 to 0.67]). Conclusions: In the Japanese population, habitual coffee drinking may be associated with reduced risk of HCC.

To examine the association between alcohol consumption and mortality in Japan, where mortality and lifestyle differ substantially from Western countries, a population-based prospective study was conducted in four public health center areas as part of the Japan Public Health Center-based prospective study on cancer and cardiovascular disease (JPHC). After excluding subjects with self-reported serious diseases at baseline, 19,231 men aged 40-59 years who reported their alcohol intake were followed from 1990 through 1996, and 548 deaths were documented. The association between all-cause mortality and alcohol consumption was J-shaped. The lowest risk was observed for men who consumed 1-149 g/week (relative risk (RR) = 0.64, 95% confidence interval (CI) 0.46, 0.88), while the highest risk was seen for men who consumed > or =450 g/week (RR = 1.32, 95% CI 1.00, 1.74), after adjustment for possible confounders. The association did not change after excluding deaths that occurred in the first 2 years of follow-up. However, the association was modified by smoking, and beneficial effects of moderate drinking were largely limited to nonsmokers. The risk of cancer death showed a similar trend, but increased more in heavy drinkers. The background characteristics of moderate drinkers were healthier than either nondrinkers or heavy drinkers. The authors conclude that moderate alcohol consumption was associated with the lowest risks of all-cause and cancer mortality, especially among nonsmokers.

The histological grade of atypia is a known prognostic indicator for breast cancer patients and correlates with many gene and chromosome alterations. To investigate the independent prognostic significance of gene and chromosome alterations in axillary node-negative (n0) breast cancers of the invasive ductal and invasive lobular types, the prevalence of eight gene and chromosome alterations and their association with histological grade and recurrence was studied in 129 consecutive patients who had undergone resection over an average follow-up period of 43.4 months. Loss of heterozygosity on 16q, 17p, 16p, 17q and 18q, p53 gene mutation and c-erbB-2 and int-2 gene amplifications were detected in 55%, 37%, 25%, 24%, 22%, 23%, 15% and 11% respectively. Individual alterations in 17p, 17q, 18q, c-erbB-2 and p53 were detected most frequently and gene and chromosome alterations tended to be accumulated in Grade 3 n0 invasive ductal/lobular carcinomas. Histological grade, 18q, int-2 and the number of these gene and chromosome alterations were significant prognostic indicators on Cox's univariate proportional hazard model, and 18q and int-2 were still significant after adjustment for histological grade. Results suggested that examination of the presence of certain gene and chromosome alterations, as well as histological grade, were effective in identifying n0 breast cancer patients at high risk of early recurrence.

Post-recurrence survival was examined in 62 breast cancer patients who had undergone curative radical mastectomies between 1974 and 1976 and suffered recurrences within 127 months of surgery. The prognostic value of 11 clinical, histological and genetic factors, including histologic grade of malignancy and amplification of oncogenes was analyzed using univariate and multivariate analyses. Not only the site of first recurrence, clinical stage and size of primary tumor at initial surgery, and disease-free period, but also histologic grade and amplification of the c-erbB-2 proto-oncogene were significant prognostic indicators of recurrent breast cancer. Multivariate analysis using Cox's regression model, histologic grade and amplification of c-erbB-2 in the primary tumor, as well as clinical stage at surgery and site of first recurrence, were shown to be major independent prognostic factors of recurrent breast cancer. Because post-recurrence prognosis was strongly influenced by the clinical, histological and genetic status of the primary breast cancer, appropriate evaluation of the primary tumor for the grade of aggressiveness of the cancer cells, as well as the extent of cancer spread, seem to be important.

Serologic tests for human T lymphotropic virus type I (HTLV-I) and hepatitis B virus infections were conducted in 1986 in two Japanese immigrant colonies located in Santa Cruz, Bolivia. A total of 322 adults (283 Japanese and 39 Bolivians) over age 35 years and 305 children (166 Japanese, 124 Bolivians, and 15 of mixed blood) aged 8-17 years were sampled at the time of a routine health checkup. The prevalence of antibody to HTLV-I was 17% in first-generation Japanese immigrants and 6% in second- or third-generation Japanese children. Prevalences among native Bolivians were 3% and 5% in adults and children, respectively. Seropositive Japanese immigrants and mothers showed clustering according to birthplace in endemic areas of Japan. The prevalence of either hepatitis B virus surface antigen (HBsAg) or antibody to HBsAg was 48% in Japanese adults, 21% in Japanese children, 13% in Bolivian adults, and 1% in Bolivian children. Seropositive adults did not show clustering according to birthplace, but children in one colony showed clustering and a narrow age range. A correlation of seropositivity between husbands and wives was found only for HTLV-I. The seropositivity was independent of whether an HTLV-I or a hepatitis B virus infection marker was present.