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Epidemiological and experimental evidence suggest that vitamin D is protective against the risk of colorectal cancer. Polymorphisms in the gene encoding vitamin D receptor (VDR), which mediates most of the known cellular effects of vitamin D, have been suggested to alter this association. Here, using a tag SNP approach, we comprehensively evaluated the role of common genetic variants in VDR and their interaction with plasma vitamin D levels in relation to colorectal cancer risk in Japanese populations. A total of 356 colorectal cancer cases and 709 matched control subjects were selected from the participants of the Japan Public Health Center-based Prospective Cohort Study. Among these subjects, 29 VDR single nucleotide polymorphisms (SNPs) were selected and genotyped, and plasma vitamin D concentrations were measured. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of colorectal cancer, with adjustment for potential confounding factors. Among the results, eight VDR SNPs, namely rs2254210, rs1540339, rs2107301, rs11168267, rs11574113, rs731236, rs3847987 and rs11574143, the latter 5 of which were located in the 3' region, were nominally associated with the risk of colorectal cancer (P = 0.01-0.048). Furthermore, of the above 5 3' region SNPs, the inverse associations for 3 SNPs (rs11574113, rs3847987 and rs11574143) appeared to be evident only in those with high plasma vitamin D concentration. However, neither of these direct and suggestive interaction analysis associations was significant after multiple testing adjustment. Overall, the findings of this study provide only limited support for an association between common genetic variations in VDR and colorectal cancer risk in the Japanese population., Competing Interests: The authors have declared that no competing interests exist.

Objective: Systematic evaluation of the association between secondhand smoke exposure and lung cancer in Japan has yet to be conducted. Here, we performed a systematic review and meta-analysis of the relationship between secondhand smoke and lung cancer in Japanese non-smokers., Methods: Relevant studies were collected from the MEDLINE and Ichushi Web databases using a combination of search terms and Medical Subject Headings. Eligible studies were identified, and relative risks or odds ratios were extracted to calculate pooled risk estimates. This procedure was performed independently by at least two authors. Stratified analyses were carried out according to study design, publication year, and whether or not potential confounding variables were accounted for. The presence of publication bias was assessed via funnel plots., Results: We identified four cohort studies and five case-control studies. Quantitative synthesis was conducted only for secondhand smoke exposure in the home during adulthood. Of the 12 populations included in meta-analysis, positive secondhand smoke exposure-lung cancer associations were observed in 11, whereas an inverse association was found in the remaining 1. The pooled relative risk of lung cancer associated with secondhand smoke exposure was 1.28 (95% confidence interval: 1.10-1.48). We found no evidence of publication bias, and a significant association remained even when potentially missing studies were included (pooled relative risk: 1.26; 95% confidence interval: 1.09-1.46). The results were stable across different subgroup analyses, including by study design, publication year, and when adjusting for confounding variables., Conclusions: Secondhand smoke exposure in the home during adulthood results in a statistically significant increase in the risk of lung cancer., (© The Author 2016. Published by Oxford University Press.)

Cytochrome P450 (CYP) 1A1 and glutathione S-transferases (GST) M1 and T1 are major enzymes in the carcinogen metabolizing pathway. We examined the association between single nucleotide polymorphisms (SNPs) of CYP1A1 (rs4646421, rs4646422 and rs1048943), GSTM1 and GSTT1 and gastric cancer risk in Japan. This is a nested case-control study (457 cases and 457 matched controls) of our population-based cohort involving 36,745 subjects who answered a baseline questionnaire and supplied blood samples. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression models. We found that CYP1A1 (rs4646422) variant allele was associated with a statistically significant increased risk of gastric cancer compared with the homozygous wild-type genotype (OR = 1.65; 95% CI = 1.17-2.32). GSTM1 null, GSTT1 null and GSTM1/T1 both or either null genotypes were associated with increased risk, but not statistically significantly. Combination of the CYP1A1 (rs4646422) variant allele and GSTM1/T1 both or either null genotypes was associated with a statistically significant increased risk compared with the combination of the CYP1A1 homozygous wild-type genotype and the GSTM1/T1 both active genotypes. In addition, compared with CYP1A1 (rs4646422) homozygous wild-type genotypes in those who were never-smokers, CYP1A1 variant alleles in those who smoked ≥30 pack-years were associated with an increased risk; neither gene-gene nor gene-environment interactions were significant. The CYP1A1 (rs4646422) polymorphism might be involved in gastric carcinogenesis among the Japanese population., (© 2016 UICC.)

Background: Longitudinal epidemiological studies require both the periodic update of intake information via repeated dietary survey and the minimization of subject burden in responding to questionnaires. We developed a 66-item Food Frequency Questionnaire (short-FFQ) for the Japan Public Health Center-based prospective Study for the Next Generation (JPHC-NEXT) follow-up survey using major foods from the FFQ developed for the original JPHC Study. For the JPHC-NEXT baseline survey, we used a larger 172-item FFQ (long-FFQ), which was also derived from the JPHC-FFQ. We compared the validity of ranking individuals by levels of dietary consumption by these FFQs among residents of selected JPHC-NEXT study areas., Methods: From 2012 to 2013, 240 men and women aged 40-74 years from five areas in the JPHC-NEXT protocol were asked to respond to the long-FFQ and provide 12-day weighed food records (WFR) as reference; 228 also completed the short-FFQ. Spearman's correlation coefficients (CCs) between estimates from the FFQs and WFR were calculated and corrected for intra-individual variation of the WFR., Results: Median CC values for energy and 53 nutrients for the short-FFQ for men and women were 0.46 and 0.44, respectively. Respective values for the long-FFQ were 0.50 and 0.43. Compared with the long-FFQ, cross-classification into exact plus adjacent quintiles with the short-FFQ ranged from 68% to 91% in men and 58% to 85% in women., Conclusions: Similar to the long-FFQ, the short-FFQ provided reasonably valid measures for ranking middle-aged and elderly Japanese for many nutrients and food groups. The short-FFQ can be used in follow-up surveys in prospective cohort studies aimed at updating diet rank information.

Objective: It remains unclear whether coffee drinking is associated with colorectal cancer risk. We performed a systematic review and meta-analysis of epidemiologic studies on this issue among the Japanese population., Methods: Original data were obtained from MEDLINE searches using PubMed or from searches of the 'Ichushi' database, complemented with manual searches. Meta-analysis was performed by using the random effects model to estimate the summary relative risk with 95% confidence interval according to the study design. The final judgment was made based on a consensus of the research group members with consideration for both epidemiological evidence and biological plausibility., Results: We identified five cohort studies and nine case-control studies. Of these, one cohort study reported a strong inverse association (in women only), whereas three case-control studies reported a strong inverse association with colon or rectal cancer. In meta-analysis, high consumption of coffee was not appreciably associated with colorectal cancer risk among cohort studies, whereas it was associated with significantly lower risk of colorectal or colon cancer among case-control studies. The summary relative risk/odds ratio (95% confidence interval) for the highest versus lowest categories of coffee consumption was 0.95 (0.77-1.17) and 0.78 (0.65-0.95) for cohort and case-control studies, respectively., Conclusions: The evidence is insufficient to support that coffee drinking increases or decreases the risk of colorectal cancer among the Japanese population., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Incidence and mortality rates for gastric cancer, the fifth most commonly diagnosed and third most deadly cancer worldwide, are highest in East Asia. We sought to identify gastric cancer risk biomarkers among eight prospective studies from China, Japan and Korea., Methods: This pooled nested case-control study included 1608 incident non-cardia gastric cancer cases and 1958 matched controls. Pre-diagnostic antibody levels to 15 Helicobacter pylori proteins were assessed using multiplex serology. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Sero-positivity to 10 H. pylori antigens (Omp, CagA, VacA, HcpC, HP 0305, GroEL, NapA, HyuA, Cad, HpaA) was associated with a 1.29- to 3.26-fold increase in odds of gastric cancer. Omp and HP 0305 consistently remained associated with gastric cancer risk after mutually adjusting for all other markers. Sero-positivity to both Omp and HP 0305 was associated with an over 4-fold increase in gastric cancer incidence (OR, 4.09; 95% CI 3.26-5.13). When limited to only those who are CagA+ H. pylori+, Omp/HP 0305 sero-positivity remained strongly associated with an over 3-fold increase in the odds of gastric cancer (OR, 3.34; 95% CI 2.27-4.91). The results were highly consistent among the cohorts., Conclusions: We have confirmed new H. pylori biomarkers that are strongly associated with gastric cancer risk, even among those infected with the known H. pylori virulence factor CagA. These results may help to design cost-efficient prevention strategies to reduce gastric cancer incidence in East Asia., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Evidence that diet is associated with breast cancer risk is inconsistent. Most of the studies have focused on risks associated with specific foods and nutrients, rather than overall diet. In this study, we aimed to evaluate the association between dietary patterns and breast cancer risk in Japanese women. A total of 49 552 Japanese women were followed-up from 1995 to 1998 (5-year follow-up survey) until the end of 2012 for an average of 14·6 years. During 725 534 person-years of follow-up, 718 cases of breast cancer were identified. We identified three dietary patterns (prudent, westernised and traditional Japanese). The westernised dietary pattern was associated with a 32 % increase in breast cancer risk (hazard ratios (HR) 1·32; 95 % CI 1·03, 1·70; P trend=0·04). In particular, subjects with extreme intake of the westernised diet (quintile (Q) Q5&#95;5th) had an 83 % increase in risk of breast cancer in contrast to those in the lowest Q1 (HR 1·83; 95 % CI 1·25, 2·68; P trend=0·01). In analyses stratified by menopausal status, postmenopausal subjects in the highest quintile of the westernised dietary pattern had a 29 % increased risk of breast cancer (HR 1·29; 95 % CI 0·99, 1·76; P trend=0·04). With regard to hormone receptor status, the westernised dietary pattern was associated with an increased risk of oestrogen receptor-positive/progesterone receptor-positivetumours (HR 2·49; 95 % CI 1·40, 4·43; P trend<0·01). The other dietary patterns were not associated with the risk of breast cancer in Japanese women. A westernised dietary pattern is associated with an increased risk of breast cancer in Japanese women.

Purpose: The aim of this study was for the first time to assess the association between glycemic index (GI), glycemic load (GL), and colorectal cancer using a prospective Japanese population-based cohort., Methods: In our study participants aged 40-69 at baseline of the Japan Public Health Center-based prospective Study (JPHC Study) in 10 prefectural public health centers (PHC) were included. Subjects responding to the five-year follow-up survey (1995-1999) without previous history of cancer and missing data were included in the current analysis n = 73,501 (men n = 34,560 and women n = 38,941). We reported results as hazard ratios (HR) and 95% confidence intervals (CI) by Cox proportional hazards modeling., Results: The average follow-up time was 12.5 years (919,276 person-years). A total of 1,468 colorectal cancer cases were detected. Overall, no significant results were observed; however, GL was inversely nonsignificantly associated with colon cancer in men HR = 0.74 (95% CI 0.51-1.09) and rectal cancer in women 0.52 (95% CI 0.24-1.14). The GL tended to be inversely associated with proximal colon cancer among men 0.62 (95% CI 0.36-1.08), while a positive association with the GI was observed among women 1.37 (95% CI 0.88-2.14). Sensitivity analyses excluding the first three years of observation showed similar results. Results stratified by diabetes status, BMI, smoking and red meat were nonsignificant., Conclusions: In conclusion, the prospective JPHC Study suggests that the GI and GL do not have a substantial impact on the risk of colorectal cancer in Japanese adults.

Diabetes mellitus constitutes a major disease burden globally, and the prevalence of diabetes continues to increase worldwide. We aimed to estimate the burden of cancer associated with type 2 diabetes mellitus in Japan between 2010 and 2030. In this study, we estimated the population attributable fraction of cancer risk associated with type 2 diabetes in 2010 and 2030 using the prevalence estimates of type 2 diabetes in Japan from 1990 to 2030, summary hazard ratios of diabetes and cancer risk from a pooled analysis of eight large-scale Japanese cohort studies, observed incidence/mortality of cancer in 2010 and predicted incidence/mortality for 2030 derived from the age-period-cohort model. Our results showed that between 2010 and 2030, the total numbers of cancer incidence and mortality were predicted to increase by 38.9% and 10.5% in adults aged above 20 years, respectively. In the number of excess incident cancer cases associated with type 2 diabetes, an increase of 26.5% in men and 53.2% in women is expected between 2010 and 2030. The age-specific analysis showed that the population attributable fraction of cancer will increase in adults aged >60 years over time, but will not change in adults aged 20-59 years. In conclusion, this study suggests a modest but steady increase in cancers associated with type 2 diabetes., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Previous studies have reported associations between diabetes and cancer risk. However, specific association of hemoglobin A1c (HbA1c) levels with cancer risk remains inconclusive. We followed 29,629 individuals (11,336 men; 18,293 women) aged 46-80 years who participated in the Japan Public Health Center-based prospective study who had HbA1c measurements available and were cancer-free at baseline. Cancer incidence was assessed by systemic surveys. We estimated hazard ratios (HRs) for cancer risk with adjustment for age sex, geographic area, body mass index, smoking status, physical activity, alcohol, coffee, vegetable and total energy consumption, and history of cardiovascular disease. After a median follow-up of 8.5 years, 1,955 individuals had developed cancer. Higher HbA1c levels within both the non-diabetic and diabetic ranges in individuals without known diabetes were associated with overall cancer risk. Compared with individuals without known diabetes and HbA1c levels of 5.0-5.4%, the HRs for all cancers were 1.27 (95% confidence interval, 1.07-1.52); 1.01 (0.90-1.14); 1.28 (1.09-1.49); and 1.43 (1.14-1.80) for individuals without known diabetes and HbA1c levels <5.0%, 5.5-5.9%, 6.0-6.4%, and ≥6.5%, respectively, and 1.23 (1.02-1.47) for individuals with known diabetes. The lowest HbA1c group had the highest risk of liver cancer, and HbA1c levels were linearly associated with the risk of all cancers after excluding liver cancer (P for linear trend, 0.004). In conclusion, our findings corroborate the notion that glycemic control in individuals with high HbA1c levels may be important not only to prevent diabetes but also to prevent cancer., (© 2015 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: To examine the association between adherence to the Japanese Food Guide Spinning Top and total and cause specific mortality., Design: Large scale population based prospective cohort study in Japan with follow-up for a median of 15 years., Setting: 11 public health centre areas across Japan., Participants: 36,624 men and 42,970 women aged 45-75 who had no history of cancer, stroke, ischaemic heart disease, or chronic liver disease., Main Outcome Measures: Deaths and causes of death identified with the residential registry and death certificates., Results: Higher scores on the food guide (better adherence) were associated with lower total mortality; the multivariable adjusted hazard ratios (95% confidence interval) of total mortality for the lowest through highest scores were 1.00, 0.92 (0.87 to 0.97), 0.88 (0.83 to 0.93), and 0.85 (0.79 to 0.91) (P<0.001 for trend) and the multivariable adjusted hazard ratio associated with a 10 point increase in food guide scores was 0.93 (0.91 to 0.95; P<0.001 for trend). This score was inversely associated with mortality from cardiovascular disease (hazard ratio associated with a 10 point increase 0.93, 0.89 to 0.98; P=0.005 for trend) and particularly from cerebrovascular disease (0.89, 0.82 to 0.95; P=0.002 for trend). There was some evidence, though not significant, of an inverse association for cancer mortality (0.96, 0.93 to 1.00; P=0.053 for trend)., Conclusion: Closer adherence to Japanese dietary guidelines was associated with a lower risk of total mortality and mortality from cardiovascular disease, particularly from cerebrovascular disease, in Japanese adults., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Although several epidemiological studies have demonstrated that cigarette smoking is an important risk factor for bladder cancer, no systematic review in the Japanese population has yet been performed. Accurate evaluation of bladder cancer risk in relation to smoking for Japanese populations can provide necessary information for Japanese policy-makers and doctors to enlighten the importance of smoking cessation. We reviewed epidemiologic data to estimate the strength of the association between cigarette smoking and bladder cancer in the Japanese population., Methods: We identified previous cohort and case-control studies, extracting data from databases in the MEDLINE (PubMed) and Ichushi. The magnitude of association and strength of evidence were evaluated in each study, and a meta-analysis was conducted to obtain summary estimates for the overall magnitude of association., Results: Three cohort and eight case-control studies were identified. Except for one case-control study, all studies showed a strong positive association between cigarette smoking and bladder cancer. The summary relative risk for ever smokers relative to never smokers was 2.14 (95% confidence interval 1.87-2.44) in a fixed-effect model., Conclusions: We conclude that cigarette smoking is a convincing risk factor for bladder cancer among Japanese., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The aim of this study was to assess the association between hepatitis B virus (HBV) and hepatitis C virus (HCV) and the risk of pancreatic cancer among Japanese adults., Methods: A total of 20,360 subjects of the Japan Public Health Center (JPHC)-based prospective study cohort II with available data on HBV and HCV infection status from blood samples were followed up until the end of 2010 for an average of 16 years. Cox proportional hazards models were employed to calculate HRs and 95% confidence intervals (CI)., Results: During 324,394 person-years, 116 newly diagnosed cases of pancreatic cancer were identified. Compared with individuals without a positive infection marker, the multivariate-adjusted HRs were 1.22 (95% CI, 0.81-1.84) for anti-HBc and 0.69 (95% CI, 0.28-1.69) for anti-HCV. There were no pancreatic cancer cases among HBsAg-positive participants., Conclusion: In the JPHC study, we did not observe a statistically significant association between hepatitis B or C and the risk of pancreatic cancer., Impact: Our results do not support an association between hepatitis B or C and the risk of pancreatic cancer., (©2015 American Association for Cancer Research.)

Background: Psychological stress is a modifiable risk factor for health outcomes and can be managed through coping mechanisms. Biological and behavioral hypotheses have been proposed to explain the association between stress coping strategies and cancer outcomes., Methods: The Japan Public Health Center-based study asked questions on coping behaviors in its 10-year follow-up survey. 55,130 subjects aged 50-79 without a history of cancer diagnosis and who provided complete answers on coping were included in analyses on cancer incidence and mortality. Hazard Ratios (HR) according to coping style were determined using Cox regression models adjusted for known confounders for cancer., Results: Mean follow-up time was 9.5 years for cancer incidence and 9.8 years for cancer mortality. The utilization of the approach-oriented coping strategy (HR=0.85, 95% CI: 0.72-0.99) and a behavior of positive reappraisal (HR=0.84, 95% CI: 0.72-0.97) was associated with a reduced risk of cancer mortality. The approach-oriented coping strategy was further associated with localized cancer incidence (HR=1.13, 95% CI: 1.01-1.27) and screening-detected cancers (HR=1.35, 95% CI: 1.15-1.58). The avoidance oriented coping strategy was inversely associated with cancer incidence (HR=0.69, 95% CI: 0.50-0.94) only after excluding events occurring in the first three years of follow-up., Conclusion: The results of this study may favor the behavioral hypothesis to explain associations between premorbid coping styles and cancer outcomes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Gastric cancer is a particularly important issue in Japan, where incidence rates are among the highest observed. In this work, we provide a risk prediction model allowing the estimation of the 10-year cumulative probability of gastric cancer occurrence. The study population consisted of 19,028 individuals from the Japanese Public Health Center cohort II who were followed-up from 1993 to 2009. A parametric survival model was used to assess the impact on the probability of gastric cancer of clinical and lifestyle-related risk factors in combination with serum anti-Helicobacter pylori antibody titres and pepsinogen I and pepsinogen II levels. Based on the resulting model, cumulative probability estimates were calculated and a simple risk scoring system was developed. A total of 412 cases of gastric cancer occurred during 270,854 person-years of follow-up. The final model included (besides the biological markers) age, gender, smoking status, family history of gastric cancer and consumption of highly salted food. The developed prediction model showed good predictive performance in terms of discrimination (optimism-corrected c-index: 0.768) and calibration (Nam and d'Agostino's χ(2) test: 14.78; p values = 0.06). Estimates of the 10-year probability of gastric cancer occurrence ranged from 0.04% (0.02, 0.1) to 14.87% (8.96, 24.14) for men and from 0.03% (0.02, 0.07) to 4.91% (2.71, 8.81) for women. In conclusion, we developed a risk prediction model for gastric cancer that combines clinical and biological markers. It might prompt individuals to modify their lifestyle habits, attend regular check-up visits or participate in screening programmes., (© 2015 UICC.)

Green tea and coffee consumption may decrease the risk of some types of cancers. However, their effects on biliary tract cancer (BTC) have been poorly understood. In this population-based prospective cohort study in Japan, we investigated the association of green tea (total green tea, Sencha, and Bancha/Genmaicha) and coffee consumption with the risk for BTC and its subtypes, gallbladder cancer, and extrahepatic bile duct cancer. The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazard model. A total of 89 555 people aged 45-74 years were enrolled between 1995 and 1999 and followed up for 1 138 623 person-years until 2010, during which 284 cases of BTC were identified. Consumption of >720 mL/day green tea was significantly associated with decreased risk compared with consumption of ≤120 mL/day (hazard ratio = 0.67 [95% confidence interval, 0.46-0.97]), and a non-significant trend of decreased risk associated with increased consumption was observed (P-trend = 0.095). In the analysis according to the location of the primary tumor, consuming >120 mL green tea tended to be associated with decreased risk of gallbladder cancer and extrahepatic bile duct cancer. When Sencha and Bancha/Genmaicha were analyzed separately, we observed a non-significant trend of decreased risk of BTC associated with Sencha but no association with Bancha/Genmaicha. For coffee, there was no clear association with biliary tract, gallbladder, or extrahepatic bile duct cancer. Our findings suggest that high green tea consumption may lower the risk of BTC, and the effect may be attributable to Sencha consumption., (© 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Limited and inconsistent studies exist on the association between the intake of fish, n - 3 polyunsaturated fatty acids (PUFA) and n - 6 PUFA and breast cancer. Fish and n - 3 PUFA support various body functions and are thought to reduce the carcinogenesis risk while n - 6 PUFA may have a positive association with cancer risk. We examined the association between intake of fish, n - 3 PUFA [including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA)] and n - 6 PUFA and breast cancer with subanalyses on estrogen (ER) and progesterone receptor (PR) status. We investigated 38,234 Japanese women aged 45-74 years from the Japan Public Health Center-based prospective study (JPHC study), and during 14.1 years of follow-up time, 556 breast cancer cases were newly diagnosed. Breast cancer risk was not associated with the intake of total fish, n - 3 PUFA and n - 6 PUFA when analyzed in totality through multivariable Cox proportional hazards regression models with age as the time scale. Intake of total n - 6 was positively associated with the development of ER+PR+ tumors [multivariable-adjusted HR Q4 vs. Q1  = 2.94 (95% CI: 1.26-6.89; ptrend  = 0.02)]. Intake of EPA was associated with a decreased breast cancer risk for ER+PR+ tumors [multivariable-adjusted HR Q2 vs. Q1  = 0.47 (95% CI: 0.25-0.89; ptrend =0.47)]. While the overall association between the intake of total fish, n - 3 PUFA and n - 6 PUFA and breast cancer risk is null, for ER+PR+ tumors, a positive association was seen between n - 6 intake and breast cancer, and a marginally significant inverse association was observed for EPA intake., (© 2015 UICC.)

Background: Most previous prospective studies in Western countries found no association between consumption of fish and n-3 (ω-3) polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), for which the main source is fish, and pancreatic cancer risk. However, prospective evidence is still lacking among populations who have a relatively higher fish consumption., Objective: We investigated the association between fish and n-3 PUFA consumption and pancreatic cancer risk in a population-based, prospective study in Japanese men and women., Design: The Japan Public Health Center-based Prospective Study (JPHC study) has enrolled 140,420 subjects. We analyzed data on 82,024 eligible participants aged 45-74 y without a history of cancer who responded to a validated food-frequency questionnaire that included 138 items in 1995 for cohort I and in 1998 for cohort II. Participants were followed through 2010. HRs and corresponding 95% CIs for the highest compared with lowest quartile were calculated by using multivariable-adjusted Cox proportional hazards regression models., Results: During 1,068,774 person-years of follow-up, 449 newly diagnosed pancreatic cancers were identified. After the exclusion of pancreatic cancer cases in the first 3 y of follow-up, we found an inverse association of marine n-3 PUFA (EPA+DPA+DHA) and DHA consumption with pancreatic cancer risk: compared with the lowest quartile, multivariate-adjusted HRs in the highest quartile were 0.70 (95% CI: 0.51, 0.95; P-trend = 0.07) and 0.69 (0.51, 0.94; P-trend = 0.03), respectively. Associations for total fish, n-3 PUFA, EPA, and DPA consumption were similar but were not significant., Conclusion: High n-3 PUFA, especially marine n-3 PUFAs, and DHA consumption was associated with a lower risk of pancreatic cancer in a population with a large variation in fish consumption, although the data apply to only a portion of the JPHC study subjects., (© 2015 American Society for Nutrition.)

Objective: The association between vegetable consumption and colorectal cancer risk remains unclear and may differ by region. We performed a systematic review and meta-analysis of epidemiologic studies on this issue among the Japanese population., Methods: A systematic review and meta-analysis was performed by searching MEDLINE through PubMed and the Ichushi database for cohort and case-control studies that were published by the end of December 2014. Associations were evaluated based on their magnitude and the strength of the evidence. Meta-analysis was performed by using the random effects model to estimate the summary relative risk with 95% confidence interval according to the study design. The final judgment was made based on a consensus of the research group members with consideration for both epidemiological evidence and biological plausibility., Results: We identified six cohort studies and 11 case-control studies on vegetable intake and colorectal cancer among the Japanese population. Of the cohort studies, one study showed a weak inverse association with colon cancer and another study showed a weak positive association with rectal cancer in men, but other studies found no associations between vegetable consumption and colon and rectal cancers. With regard to case-control studies, one study found a strong inverse association with colon cancer, and three studies showed a weak-to-strong inverse association with rectal cancer. In meta-analysis, the summary relative risk (95% confidence interval) for the highest vs. the lowest categories of vegetable consumption were 1.00 (0.92-1.10) and 0.75 (0.59-0.96) for cohort and case-control studies, respectively., Conclusions: There was insufficient evidence to support an association between intake of vegetables and the risk of colorectal cancer among the Japanese population., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Several studies have assessed the association between hepatitis B virus (HBV) and hepatitis C virus (HCV) and non-Hodgkin's lymphoma. However, few studies are cohort by design, conducted within the Asian context and even fewer studies consider other lymphoid malignancies. The aim of this study was to assess the association between HBV and HCV and the risk of lymphoid malignancies among Japanese adults., Materials and Methods: The Japan Public Health Center prospective-based Study Cohort II was initiated in 1993/1994. 20,360 subjects with available data on HBV and HCV infection status from blood samples were followed up until the end of 2010 for an average of 16 years. During 324,139 person-years, 120 newly diagnosed cases of lymphoid malignancies were identified. Cox proportional hazards models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95%CIs)., Results: Of 20,360 subjects, 508 were HBsAg positive, 11,035 were anti-HBc positive, and 1,129 subjects were anti-HCV positive at baseline. The presence of HBsAg was positively associated with malignant lymphoma, especially with non-Hodgkin's lymphoma (HR=3.56, 95%CI=1.37-9.18) and diffuse large B-cell lymphoma (HR=7.22, 95%CI=2.34-22.29). In contrast, no clear association was observed between the presence of anti-HBc and anti-HCV., Conclusion: In conclusion, HBsAg but not anti-HBc or anti-HCV was positively associated with malignant lymphoma, particularly non-Hodgkin's lymphoma and diffuse large B-cell lymphoma in Japanese adults., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

International reviews have concluded that consumption of fruit and vegetables might decrease the risk of lung cancer. However, the relevant epidemiological evidence still remains insufficient in Japan. Therefore, we performed a pooled analysis of data from four population-based cohort studies in Japan with >200 000 participants and >1700 lung cancer cases. We computed study-specific hazard ratios by quintiles of vegetable and fruit consumption as assessed by food frequency questionnaires. Summary hazard ratios were estimated by pooling the study-specific hazard ratios with a fixed-effect model. In men, we found inverse associations between fruit consumption and the age-adjusted and area-adjusted risk of mortality or incidence of lung cancer. However, the associations were largely attenuated after adjustment for smoking and energy intake. The significant decrease in risk among men remained only for a moderate level of fruit consumption; the lowest summary hazard ratios were found in the third quintile of intake (mortality: 0.71, 95% confidence interval 0.60-0.84; incidence: 0.83, 95% confidence interval 0.70-0.98). This decrease in risk was mainly detected in ever smokers. Conversely, vegetable intake was positively correlated with the risk of incidence of lung cancer after adjustment for smoking and energy intake in men (trend P, 0.024); the summary hazard ratio for the highest quintile was 1.26 (95% confidence interval 1.05-1.50). However, a similar association was not detected for mortality from lung cancer. In conclusion, a moderate level of fruit consumption is associated with a decreased risk of lung cancer in men among the Japanese population., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Coffee is a commonly consumed beverage which contains several potential anticarcinogenic and chemopreventive compounds, and has been hypothesized to have protective effects in colorectal neoplasia. However, the limited available data on coffee consumption in relation to colorectal adenoma (CRA), a precursor lesion to most colorectal cancers, remain largely inconsistent. In this study, we evaluated the association of coffee intake with the risk of CRA in a middle-aged Japanese population. Study subjects were selected from examinees who underwent total colonoscopy as part of a cancer screening program and responded to self-administered dietary and lifestyle questionnaires. A total of 738 patients with adenoma and 697 controls were included in the study. Coffee intake was assessed with a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) of CRA, with adjustment for potential confounding factors. High coffee consumption was associated with a reduced risk of CRA, with a multivariate-adjusted OR for the highest versus lowest quartile of coffee intake of 0.67 (95% CI = 0.48-0.93; ptrend  = 0.02). The inverse association of coffee intake was limited to proximal (OR = 0.64; 95%CI = 0.44-0.95; ptrend  = 0.04) and distal colon adenoma (OR = 0.62; 95%CI = 0.39-0.99; ptrend  = 0.06), and appeared to be more evident with small (OR = 0.68; 95%CI = 0.49-0.96; ptrend  = 0.04) and single adenomas (OR = 0.65; 95%CI = 0.44-0.95; ptrend  = 0.02). Green tea intake was not found to be associated with CRA risk. This study provides support for the protective effect of coffee drinking on colon adenomas, a precursor of colon cancer., (© 2014 UICC.)

Purpose: We examined the association between green tea consumption and mortality due to all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries, and other causes of death in a large-scale population-based cohort study in Japan., Methods: We studied 90,914 Japanese (aged between 40 and 69 years) recruited between 1990 and 1994. After 18.7 years of follow-up, 12,874 deaths were reported. The association between green tea consumption and risk of all causes and major causes of mortality was assessed using the Cox proportional hazards regression model with adjustment for potential confounders., Results: Hazard ratios for all-cause mortality among men who consumed green tea compared with those who drank less than 1 cup/day were 0.96 (0.89-1.03) for 1-2 cups/day, 0.88 (0.82-0.95) for 3-4 cups/day, and 0.87 (0.81-0.94) for more than 5 cups/day (P for trend <.001). Corresponding hazard ratios for women were 0.90 (0.81-1.00), 0.87 (0.79-0.96), and 0.83 (0.75-0.91; P for trend <.001). Green tea was inversely associated with mortality from heart disease in both men and women and mortality from cerebrovascular disease and respiratory disease in men. No association was found between green tea and total cancer mortality., Conclusions: This prospective study suggests that the consumption of green tea may reduce the risk of all-cause mortality and the three leading causes of death in Japan., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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 full responders. More than one non-responder category should therefore be considered when interpreting data pertaining to psychosocial questionnaires in longitudinal studies., (© The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Despite the rising consumption of coffee worldwide, few prospective cohort studies assessed the association of coffee intake with mortality including total and major causes of death., Objective: We aimed to investigate the association between habitual coffee drinking and mortality from all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries, and other causes of death in a large-scale, population-based cohort study in Japan., Design: We studied 90,914 Japanese persons aged between 40 and 69 y without a history of cancer, cerebrovascular disease, or ischemic heart disease at the time of the baseline study. Subjects were followed up for an average of 18.7 y, during which 12,874 total deaths were reported. The association between coffee intake and risk of total and cause-specific mortality was assessed by using a Cox proportional hazards regression model with adjustment for potential confounders., Results: We showed an inverse association between coffee intake and total mortality in both men and women. HRs (95% CIs) for total death in subjects who consumed coffee compared with those who never drank coffee were 0.91 (0.86-0.95) for <1 cup/d, 0.85 (0.81-0.90) for 1-2 cups/d, 0.76 (0.70-0.83) for 3-4 cups/d, and 0.85 (0.75-0.98) for >5 cups/d (P-trend < 0.001). Coffee was inversely associated with mortality from heart disease, cerebrovascular disease, and respiratory disease., Conclusion: With this prospective study, we suggest that the habitual intake of coffee is associated with lower risk of total mortality and 3 leading causes of death in Japan., (© 2015 American Society for Nutrition.)

To date, the association between diabetes mellitus (DM) and gastric cancer has been controversial, including the underlying mechanism. We investigated the association between plasma diabetic biomarkers (insulin, C-peptide, and blood glucose) and gastric cancer risk. In addition, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were calculated. A total of 36,745 subjects aged 40-69 years in the Japan Public Health Center-based prospective study (JPHC) who returned the baseline questionnaire and provided blood samples were followed from 1990 to 2004. In the present analysis, 477 cases and 477 matched controls were used. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for developing gastric cancer were calculated using conditional logistic regression models. Plasma insulin was positively associated with increased risk of gastric cancer; compared to tertile 1, ORs were 1.69 (95% CI = 1.11-2.59) and 2.01 (1.19-3.38) for tertiles 2 and 3, respectively (p for trend = 0.009). In men, C-peptide was also positively associated with a significant risk; corresponding ORs were 1.42 (0.85-2.38) and 1.91 (1.03-3.54), respectively (p for trend = 0.04). These findings were confirmed for blood samples from the fasting group (≥8 hr after a meal). Higher HOMA-IR was also associated with increased risk, whereas no association was observed for blood glucose. Our findings suggest that Japanese population with higher insulin and C-peptide levels derived from insulin resistance have an elevated risk of gastric cancer., (© 2014 UICC.)

Background: Evidence suggests that estrogen plays a preventive role in primary liver cancer development, and it might be thought that isoflavones, which are structurally similar to estrogens and bind to estrogen receptors, are associated with the risk of liver cancer. We investigated this suspected association by measuring plasma concentrations of isoflavones in a nested case-control study of a population-based prospective cohort in Japan., Methods: From 18,628 target participants ages 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or hepatitis C virus infection at baseline (n = 1,544). Among these, 90 (28 women and 62 men) were newly diagnosed with primary liver cancer from 1993 through 2006; they were matched with 175 controls (54 women and 121 men). Plasma concentrations of isoflavones (genistein, daidzein, glycitein, and equol) were measured using triple quadrupole tandem liquid chromatography-mass spectrometry. The ORs of liver cancer development based on plasma concentrations were estimated with a conditional logistic regression model., Results: Basically, distributions of plasma isoflavone concentrations did not differ between the cases and controls. No statistically significant associations of genistein, daidzein, glycitein, and equol with primary liver cancer risk were found in either women or men., Conclusions: In middle-aged Japanese women and men with hepatitis virus infection, plasma isoflavones were unassociated with the occurrence of primary liver cancer., Impact: The role of isoflavones in liver carcinogenesis merits further study using both biomarkers and data on dietary intake of isoflavones. Cancer Epidemiol Biomarkers Prev; 24(3); 532-7. ©2014 AACR., (©2014 American Association for Cancer Research.)

Background: While several studies have provided support for a positive association between meat intake and colorectal neoplasia, the role of heterocyclic amines (HCA), which is hypothesized to underline this relation, has been less consistent. We evaluated the association of HCA intake with colorectal adenoma risk in a case-control study in a middle-aged Japanese population., Methods: Study subjects were 738 patients with adenoma and 697 controls who underwent total colonoscopy between 2004 and 2005 and responded to self-administered lifestyle and dietary questionnaires. HCA exposure concentration was estimated from meat and fish intake based on an HCA database that was validated against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) values measured in human hair. Logistic regression models were used to estimate ORs and 95% confidence interval (CI) for the association between HCA and colorectal adenoma risk after adjusting for potential confounders., Results: High intake of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and total HCA was associated with an increased risk of colorectal adenoma in women but not in men. The multivariate-adjusted OR for the highest versus lowest quartile in women was 2.10 (95% CI, 1.20-3.67; Ptrend = 0.01) for MeIQ and 1.73 (95% CI, 0.99-3.01; Ptrend = 0.03) for total HCA. No clear association with PhIP or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) estimates and no effect modification by NAT2 acetylation genotype was observed., Conclusions: This study suggests that high MeIQ and total HCA estimates are positively associated with colorectal adenoma risk., Impact: The findings add to evidence that HCA may play a role in colorectal carcinogenesis in humans. Cancer Epidemiol Biomarkers Prev; 24(3); 613-20. ©2015 AACR., (©2015 American Association for Cancer Research.)

Objective: Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women., Design: Prospective cohort study., Setting: Ten public health centre areas in Japan., Population: Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey questionnaire., Methods: Intakes of soy foods as well as other covariates were assessed in 1995-1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI)., Main Outcome Measure: Incidence of endometrial cancer., Results: During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84-1.22)., Conclusion: In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Background: The aim of the study was to investigate trends in cancer prognosis by examining the relationship between period of diagnosis and probability of death from cancer in a population-based cohort., Methods: Within a cohort of Japanese men and women aged 40-69 years and free of prior diagnosis of cancer and cardiovascular disease at baseline, data from 4403 patients diagnosed with cancer between 1990 and 2006 and followed up until 2012 were analyzed using survival regression models to assess the presence of an effect of the period of diagnosis (before 1998 versus after 1998) on the risk of dying from cancer., Results: We noted a significant decrease in risk of dying from cancer among individuals diagnosed after 1998 with lung cancer (hazard ratio [HR]=0.676 [0.571-0.800]) or colorectal cancer (HR=0.801 [0.661-0.970]). A decrease in the estimated five-year probability of death from cancer was also noted between the first (before 1998) and the second (after 1998) period of diagnosis for lung and colorectal cancers (e.g., 85.4% vs. 73.3% for lung cancer and 44.6% vs. 37.7% for colorectal cancer, respectively, for stage III in men aged 60 at diagnosis)., Conclusions: This study presented the first scientific evidence of improvement in prognosis for lung and colorectal cancer patients in a population-based cohort in Japan. Our results suggest that recent advances in cancer treatment could have influenced cancer survival differently among lung, colorectal and gastric cancers., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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 <150 g/week (P for interaction = 0.02). ALDH2 A allele carriers who drink ≥150 g/week also had an increased risk (OR = 2.08, 95% CI = 1.05-4.12) relative to GG genotype carriers who drink 0 to < 150 g/week (P for interaction = 0.08). To find the relation between alcohol consumption and gastric cancer risk, it is important to consider both alcohol consumption level and ADH1C and ALDH2 polymorphisms., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Dietary fiber may reduce the risk of prostate cancer, possibly by increasing circulating concentrations of sex hormone-binding globulin and improving insulin sensitivity. However, results from previous epidemiologic studies of fiber intake and prostate cancer are inconsistent, and to our knowledge, no study has comprehensively evaluated the effects of soluble and insoluble fiber on prostate cancer in Asia., Objective: The objective was to examine the association between fiber intake and prostate cancer in Japanese men., Design: We conducted a population-based prospective study in 43,435 Japanese men aged 45-74 y. Participants responded to a validated questionnaire, which included 138 food items. Follow-up was from 1995 through 2009. HRs and 95% CIs of incidence were calculated according to quartiles of fiber intake., Results: During the 11.6-y follow-up, of the 825 men newly diagnosed with prostate cancer, 213 had advanced-stage cancer, 582 had organ-localized disease, and 30 had an undetermined stage of disease. Among them, 217 cases were detected by subjective symptoms. Total fiber was not associated with total or advanced prostate cancer, with respective multivariable HRs for the highest and lowest quartiles of 1.00 (95% CI: 0.77, 1.29; P-trend = 0.97) and 0.67 (95% CI: 0.42, 1.07; P-trend = 0.30). Total fiber and insoluble fiber intake were associated with a decreased risk of advanced cancers detected by subjective symptoms, with multivariate HRs (95% CIs) across increasing quartiles of 1.00, 0.58, 0.62, and 0.44 (0.21, 0.92; P-trend = 0.05) for total fiber and 1.00, 0.60, 0.52, and 0.46 (0.22, 0.93; P-trend = 0.04) for insoluble fiber. Soluble fiber intake showed no association with prostate cancer., Conclusions: Dietary fiber is inversely associated with advanced prostate cancer detected by subjective symptoms even among populations with relatively low intake, such as Japanese. These results suggest that a very low intake of dietary fiber is associated with an increased risk of prostate cancer., (© 2015 American Society for Nutrition.)

Objective: The potential associations of diabetes mellitus with malignant neoplasms including liver cancer have become a great concern from both clinical and preventive perspectives. Although sufficient evidence for a positive association between diabetes and liver cancer already exists, it would be informative to summarize up-to-date epidemiologic data in Japan., Methods: We systematically reviewed epidemiologic studies on diabetes and liver cancer among Japanese populations. Original data were obtained by searching the MEDLINE (PubMed) and Ichushi databases, complemented with 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 biological plausibility., Results: We identified 19 cohort studies, one pooled-analysis of seven cohort studies, and seven case-control studies. Of 24 relative risk estimates of liver cancer for diabetes reported in those cohort studies, 17 showed a weak to strong positive association, six revealed no association and one demonstrated a weak inverse association (summary relative risk 2.10, 95% confidence interval 1.60-2.76). Ten relative risk estimates from the case-control studies showed a weak to strong positive association (n = 9) or no association (n = 1; summary relative risk 2.32, confidence interval 1.73-3.12). Overall, the summary relative risk became 2.18 (confidence interval 1.78-2.69). Heterogeneity in relative risks was significant for the difference in categories of study population (P = 0.01), but not in study type (P = 0.39) or sex (P = 0.33)., Conclusions: Diabetes mellitus 'probably' increases the risk of liver cancer among the Japanese population., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: In many developed countries, socioeconomic status is associated with cancer incidence and survival. However, research in Japan is sparse. We examined the association between neighborhood deprivation based on the Japanese Deprivation Index and the risk of incidence, mortality and survival from total and major cancers in the Japan Public Health Center-based Prospective Study., Methods: 86,112 participants were followed through the end of 2009. A total of 10,416 incident cases and 5,510 deaths from cancer were identified among 1,348,437 person-years of follow-up (mean follow-up: 15.7 years). The Japanese deprivation index was used to access neighborhood deprivation. Hazard ratios and 95% confidence intervals were calculated by Cox regression analysis., Results: We found no associations between neighborhood deprivation index and the incidence of total and major cancers. In some cancer risks or deaths, however, we found positive or inverse associations with a higher deprivation index, such as a decreased risk of colorectal cancer incidence and an increased risk of liver cancer incidence and deaths in women., Conclusion: Although some positive or inverse associations were detected for specific sites, the neighborhood deprivation index has no substantial overall association with the risk of incidence, mortality and survival from cancer in the Japanese population.

Objective: The association between meat consumption and colorectal cancer remains inconsistent among Asians. The present study systematically evaluated and meta-analyzed epidemiologic studies on the association between consumption of total and specific meats and colorectal cancer risk among Japanese., Methods: Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented with manual searches. The associations were evaluated based on the strength of evidence, the magnitude of association and biologic plausibility. A meta-analysis was performed according to total meat, red and processed meat as well as poultry and site-specific cancers., Results: Six cohort studies and 13 case-control studies were identified. In cohort studies, most investigations found no association between total meat consumption and colon/rectal cancer, and several studies showed a weak-to-moderate positive association of red meat and processed meat consumption with colon/rectal cancer. The majority of case-control studies showed no association between total meat consumption and colon and rectal cancer; however, several ones reported a weak-to-strong positive association of red and processed consumption with colon and rectal cancer. In meta-analysis, the summary relative risks (95% confidence interval) for the highest versus lowest categories of red meat consumption were 1.16 (1.001-1.34) and 1.21 (1.03-1.43) for colorectal and colon cancer, respectively, and those for processed meat consumption were 1.17 (1.02-1.35) and 1.23 (1.03-1.47) for colorectal and colon cancer, respectively. Poultry consumption was associated with lower risk of rectal cancer; summary relative risk (95% confidence interval) was 0.80 (0.67-0.96)., Conclusions: High consumption of red meat and processed meat possibly increases risk of colorectal cancer or colon cancer among the Japanese population., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Colorectal cancer (CRC) incidence rate increased rapidly in Japan between the 1950s and 1990s. We examined the association between rice intake and CRC risk in comparison with bread, noodles and cereal among Japanese adults enrolled in the Japan Public Health Center-based prospective Study., Methods: A total of 73,501 Japanese men and women were followed-up from 1995 to 1999 until the end of 2008 for an average of 11 years. During 801,937 person-years of follow-up, we identified 1276 incident cases of CRC. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC for rice, noodle, bread and cereal intake were calculated by Cox proportional hazards model., Results: Overall, no significant association was observed for the highest quartile of rice intake compared with the lowest and the risk of CRC and its subsites in men (HR, 0.77; 95% CI, 0.56-1.07) and women (HR, 1.10; 95% CI, 0.71-1.68). However, a non-significant inverse trend was observed between rice intake and rectal cancer in men. No clear patterns of association were observed in bread, noodle and cereal intake., Conclusion: Our findings suggest that the consumption of rice does not have a substantial impact on the risk of CRC in the Japanese population.

Objective: We reviewed epidemiological studies of soy intake and breast cancer among Japanese women. This report is one among a series of articles by our research group, which is evaluating the existing evidence concerning the association between health-related lifestyles and cancer., Methods: Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility., Results: Five cohort studies and six case-control studies were identified. Among the cohort studies, two studies observed that total soy intake (in terms of total amounts of soy foods or soy isoflavones) was associated with a moderate (0.5 ≤ relative risk ≤ 0.67 with statistical significance) or strong (relative risk ≤ 0.5 with statistical significance) risk reduction of breast cancer in postmenopausal women. Among the case-control studies, two studies reported a weak (0.67 ≤ odds ratio ≤ 1.5 with statistical significance or 0.5 ≤ odds ratio ≤ 0.67 without statistical significance) inverse association between total soy intake and the risk of breast cancer. In the former, this association was observed in all women combined-premenopausal and postmenopausal women-but in the latter, the association was confined to postmenopausal women. The associations of intakes of individual soy foods with the risk of breast cancer were generally null. There is some evidence that supports the biological plausibility of a protective effect of isoflavones on breast cancer risk., Conclusions: We conclude that soy intake possibly decreases the risk of breast cancer among Japanese women.

Purpose: Cross-sectional studies have shown an association between different coping styles and suicidal behavior. It is unknown whether there is any prospective association between coping behaviors and suicide in the general population., Methods: The study population consisted of participants of the Japanese Public Health Center-based Prospective Study. In the 10-year follow-up questionnaire, subjects aged 50-79 years were asked how they handle daily problems. Coping behaviors were used to determine two coping strategies (approach coping and avoidance coping). Of 99,439 subjects that returned the 10-year follow-up questionnaire, 70,213 subjects provided complete answers on coping and were included in our analyses. Cox regression models, adjusted for confounders, were used to determine the risk of committing suicide according to coping style. Mean follow-up time was 8.8 years., Results: Two coping behaviors were significantly associated with suicide over time: planning (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.41-0.98) and self-blame (HR, 2.20; 95% CI, 1.29-3.76). Of the coping strategies, only the avoidance coping strategy was significantly associated with suicide (HR, 2.45; 95% CI, 1.24-4.85)., Conclusions: For the first time, two coping behaviors and one coping strategy have been shown to have a significant prospective association with suicide in a general population., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Although alcohol and smoking have not been established as risk factors for prostate cancer, they are important risk factors for other human cancers and potentially major avoidable factors. Alcohol drinkers and smokers might be less likely to get screening, which might lead to attenuation of the positive association. Here, we investigated the association of alcohol drinking and smoking and prostate cancer according to stage, as well as prostate cancer detected by subjective symptoms, in a large prospective study among Japanese men. The Japan Public Health Center-based prospective study (JPHC study) was established in 1990 for Cohort I and in 1993 for Cohort II. Subjects were 48,218 men aged 40-69 years who completed a questionnaire, which included their alcohol and smoking habits at baseline, and who were followed until the end of 2010. During 16 years of follow-up, 913 men were newly diagnosed with prostate cancer; of whom 248 had advanced cases, 635 were organ-localized and 30 were of an undetermined stage. Alcohol consumption was dose-dependently associated with advanced prostate cancer [nondrinkers: reference, 0-150 g/week: hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 0.83-1.82; 150-300 g/week: HR = 1.51, 95% CI = 1.04-2.19; ≥ 300 g/week: HR = 1.41, 95% CI = 0.97-2.05, p for trend = 0.02]. The positive association was not substantially changed among cancers detected by subjective symptoms. Smoking was inversely associated with prostate cancer among total subjects, but tended to increase the risk of advanced prostate cancer detected by subjective symptoms. In conclusion, abstinence from alcohol and prohibition of smoking might be important factors in the prevention of advanced prostate cancer., (© 2013 UICC.)

Background: A positive association between body mass index (BMI) and breast cancer risk among postmenopausal women has been reported, and a weak inverse association has been suggested among premenopausal women from studies in the Western population. The effects of BMI on breast cancer have remained unclear among the Asian population, especially in premenopausal women., Methods: We assessed the associations between BMI and breast cancer incidence by a pooled analysis from eight representative large-scale cohort studies in Japan. Cancer incidence was mainly confirmed through regional population-based cancer registries and/or through active patient notification from major local hospitals. Breast cancer was defined as code C50 according to ICD10. Pooled estimates of the hazard ratios (HRs) and 95% confidence interval (CIs) for breast cancer were calculated using random-effects models., Results: Analytic subjects were 183 940 women, 1783 of whom had breast cancer during 2 194 211 person-years of follow-up. A positive association between BMI and the risk of postmenopausal breast cancer was observed (trend P<0.001). The HRs for premenopausal breast cancer were 1.05 (95% CI 0.56-1.99), 1.07 (95% CI 0.76-1.52), 0.91 (95% CI 0.64-1.30), 1.15 (95% CI 0.76-1.73), 1.45 (95% CI 0.71-2.94), and 2.25 (95% CI 1.10-4.60), respectively, in BMIs of <19, 19 to <21, 21 to <23, 25 to <27, 27 to <30, and ≥30 kg/m2. These results were not substantially altered after excluding the patients who were diagnosed with breast cancer in the first 2 years of follow-up., Conclusions: The increased risk of postmenopausal breast cancer among women with higher BMIs was confirmed in Japanese. A borderline-significant positive association between BMI and premenopausal breast cancer was observed, suggesting that body mass in Asian women might have opposite effects on breast cancer compared with Western women.

Background: Epidemiological evidence for the impact of fruit and vegetable intake on breast cancer risk among the Japanese populations is scarce., Objective: The purpose of this study was to evaluate the association between fruit and vegetable intake and breast cancer risk among 47,289 Japanese women., Design: The study was conducted under a population-based prospective cohort design. Dietary assessment was performed using a validated food frequency questionnaire. A Cox proportional hazards regression model was used to calculate relative risks (RRs) and their corresponding 95 % confidence intervals (CIs)., Results: During an average of 10.2 years of follow-up, 452 cases of breast cancer were newly diagnosed. No association with breast cancer risk was seen for intake of total fruits and vegetables, cruciferous vegetables, green-leaf vegetables, yellow vegetables, or tomato products in overall or postmenopausal women. Cruciferous vegetable intake was associated with a statistically significant decrease in risk of premenopausal breast cancer [multivariable-RRQ4 vs. Q1 = 0.64 (95 % CI = 0.38-1.10; p trend = .046)] and showed a marginally inverse association with ER+ PR+ tumors [RRper 100 g increment = 0.64 (95 % CI = 0.41-1.00)]. In contrast, positive associations were seen between intake of total fruits and citrus fruits and breast cancer risk in overall and premenopausal women. However, these associations for fruit were all attenuated with additional adjustment for vitamin C intake., Conclusions: Our results suggest an overall null association between total fruit and vegetable intake and breast cancer risk. Intake of cruciferous vegetable showed a statistically significant association with a decreased risk of breast cancer among premenopausal women.

Background: Excess body weight is an independent risk factor for primary liver cancer, and the role of adiponectin in the pathogenesis of obesity-related malignancies is a focus of research interest. Few prospective studies have examined the association between circulating adiponectin and liver cancer risk, so we investigated this association in a nested case-control study of a population-based prospective cohort in Japan., Methods: From 18,628 target participants of ages 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or C virus infection at baseline (n = 1,544). Among these, 90 were newly diagnosed with primary liver cancer from 1993 through 2006, and matched to 177 controls. The ORs of liver cancer development based on plasma levels of adiponectin were estimated with a conditional logistic regression model., Results: Median values of total and high-molecular-weight (HMW) adiponectin tended to be higher in the patients with liver cancer, and plasma levels of adiponectin were positively associated with liver cancer risk. Body mass index- and diabetes-adjusted ORs for the highest tertile of total and HMW adiponectin levels versus the lowest were 3.30 [95% confidence interval (CI), 1.45-7.53; Ptrend < 0.01] and 3.41 (95% CI, 1.50-7.73; Ptrend < 0.01), respectively. There was no effect modification by body mass index and diabetes., Conclusions: Higher plasma adiponectin levels were associated with an increased risk of primary liver cancer in middle-aged Japanese adults with hepatitis virus infection., Impact: Circulating adiponectin levels may be a risk marker for primary liver cancer., (©2013 AACR.)

Objective: The present work aims to provide 10-year estimates of the probability of cancer occurrence in the Japanese population based on age, sex, and the pattern of adherence to five healthy lifestyle habits., Methods: The study population consisted of 74,935 participants in the Japan Public Health Center-Based Prospective Study (aged 45 to 74 years) who answered a 5-year follow-up questionnaire about various lifestyle habits between 1995 and 1999. The relationship between five previously identified healthy lifestyle habits (never smoking, moderate or no alcohol consumption, adequate physical activity, moderate salt intake, and appropriate body mass index) and cancer occurrence was assessed using a sex-specific parametric survival model., Results: Compared to individuals not adhering to any of the five habits, never-smoking men had a nearly 30% reduction in the 10-year probability of cancer occurrence (e.g., 20.5% vs. 28.7% at age 70), and never-smoking women had a 16% reduction (e.g., 10.5% vs. 12.5% at age 70). Adherence to all five habits was estimated to reduce the 10-year probability of cancer occurrence by 1/2 in men and 1/3 in women., Conclusion: By quantifying the impact of lifestyle habits on the probability of cancer occurrence, this study emphasizes the importance of lifestyle improvement., (© 2013.)

Although a growing body of evidence suggests a link between diabetes and cancer, it is not clear whether diabetes independently increases the risk of cancer. We conducted a comprehensive assessment of the association between pre-existing diabetes and total and site-specific cancer risk based on a pooled analysis of eight cohort studies in Japan (>330 000 subjects). We estimated a summary hazard ratio by pooling study-specific hazard ratios for total and site-specific cancer by using a random-effects model. A statistically increased risk was observed for cancers at specific sites, such as colon (hazard ratio; HR = 1.40), liver (HR = 1.97), pancreas (HR = 1.85) and bile duct (HR = 1.66; men only). Increased risk was also suggested for other sites, and diabetes mellitus was associated with an overall 20% increased risk in total cancer incidence in the Japanese population. The association between these two diseases has important implications for reiterating the importance of controlling lifestyle factors and may suggest a possible strategy for cancer screening among patients with diabetes. Studies continuously investigating the risk factors for diabetes are also important., (© 2013 Japanese Cancer Association.)

Background: Total or red meat intake has been shown to be associated with a higher risk of mortality in Western populations, but little is known of the risks in Asian populations., Objective: We examined temporal trends in meat consumption and associations between meat intake and all-cause and cause-specific mortality in Asia., Design: We used ecological data from the United Nations to compare country-specific meat consumption. Separately, 8 Asian prospective cohort studies in Bangladesh, China, Japan, Korea, and Taiwan consisting of 112,310 men and 184,411 women were followed for 6.6 to 15.6 y with 24,283 all-cause, 9558 cancer, and 6373 cardiovascular disease (CVD) deaths. We estimated the study-specific HRs and 95% CIs by using a Cox regression model and pooled them by using a random-effects model., Results: Red meat consumption was substantially lower in the Asian countries than in the United States. Fish and seafood consumption was higher in Japan and Korea than in the United States. Our pooled analysis found no association between intake of total meat (red meat, poultry, and fish/seafood) and risks of all-cause, CVD, or cancer mortality among men and women; HRs (95% CIs) for all-cause mortality from a comparison of the highest with the lowest quartile were 1.02 (0.91, 1.15) in men and 0.93 (0.86, 1.01) in women., Conclusions: Ecological data indicate an increase in meat intake in Asian countries; however, our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat, poultry, and fish/seafood. Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries.

Objective: To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians., Design: Pooled analyses of 20 prospective cohorts in Asia, including data from 835,082 east Asians and 289,815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability., Setting: General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh)., Participants: 1,124,897 men and women (mean age 53.4 years at baseline)., Main Outcome Measures: Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes., Results: 49,184 cardiovascular deaths (40,791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12)., Conclusions: Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

Objective: The association between fish consumption and colorectal cancer risk remains inconclusive. The present study systematically reviewed and meta-analyzed epidemiologic data on the association between fish consumption and colorectal cancer risk among Japanese., Methods: Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented with manual searches. The associations were evaluated based on the strength of evidence, the magnitude of association and biologic plausibility. Meta-analysis was conducted according to the study design., Results: Five cohort studies and 12 case-control studies were identified. Fish consumption was not significantly associated with colorectal, colon or rectal cancer risks. One cohort study showed a weak positive association with colorectal cancer, and another showed a weak inverse association with colon cancer in men and a moderate and weak inverse association with colon and rectal cancers in women. As regards case-control studies, four studies reported a weak inverse association, whereas one showed a weak positive association with colon cancer. Regarding rectal cancer, four case-control studies showed a weak inverse association, but two reported a weak-to-moderate positive association. The pooled relative risk/odds ratio (95% confidence interval) of colorectal cancer for the highest versus lowest category of fish consumption was 1.03 (0.89-1.18) and 0.84 (0.75-0.94) for cohort and case-control studies, respectively., Conclusions: There was insufficient evidence to support an association between fish consumption and the risk of colorectal cancer among Japanese.

Background: Limited evidence is available concerning the impact of the combination of Helicobacter pylori- (H. pylori) and cytotoxin-associated gene-A (CagA)-positivity on the risk of myocardial infarction (MI) and stroke, particularly in Asian populations, in which the prevalence of H. pylori infection is high., Methods: A prospective, nested case-control study was conducted to examine the association between H. pylori and CagA and risk of MI and stroke within a cohort of 29,876 men and women aged 40-69 years with no history of heart disease, stroke or cancer. Participants completed a risk factor survey and donated blood samples between 1990 and 1994. Systematic cardiovascular surveillance was performed through 2002. One control for each stroke case and two controls for each MI case were matched by sex, age, date of blood sampling, time since last meal and study location., Results: During the follow-up period, there were 600 strokes and 106 MIs. H. pylori-IgG positivity was not associated with the risk of MI, while CagA positivity tended to be associated with it (OR = 1.72, 95%CI: 0.91-3.26, p = 0.10). We found no association between H. pylori or CagA and risk of stroke., Conclusions: H. pylori infection was not significantly associated with risk of MI and stroke among middle-aged Japanese. However, CagA positivity tended to be associated with MI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)