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Background: Colorectal Cancer (CRC) has been molecularly classified into several subtypes according to tumor, stromal, and immune components. Here, we investigated whether the preventive effect of vitamin D on CRC varies with subtypes defined by Vitamin D receptor (VDR) expression in tumors and their surrounding stroma, along with the association of somatic mutations in CRC. Methods: In a population-based prospective study of 22,743 Japanese participants, VDR expression levels in tumors and their surrounding stroma were defined in 507 cases of newly diagnosed CRC using immunohistochemistry. Hazard ratios of CRC and its subtypes according to dietary vitamin D intake were estimated using multivariable Cox proportional hazards models. Results: Dietary vitamin D intake was not associated with CRC or its subtypes defined by VDR expression in tumors. However, an inverse association was observed for CRC with high VDR expression in the stroma (the highest tertile vs the lowest tertile: 0.46 [0.23–0.94], Ptrend = 0.03), but not for CRC with low VDR expression in the stroma (Pheterogeneity = 0.02). Furthermore, CRC with high VDR expression in the stroma had more somatic TP53 and BRAF mutations and fewer APC mutations than those with low VDR expression in the stroma. Conclusions: This study provides the first evidence that the preventive effect of vitamin D on CRC depends on VDR expression in the stroma rather than in the tumors. CRC with high VDR expression in the stroma is likely to develop through a part of the serrated polyp pathway, which tends to occur with BRAF but not with APC mutations. [ABSTRACT FROM AUTHOR]

Purpose: Evidence from several cohorts has suggested that a higher intake of isoflavone is associated with lower risk of lung cancer in never smokers, but the association has not been investigated by histologic type of lung cancer. Adenocarcinoma is a common histologic type found in never smokers. We hypothesized that a higher intake of isoflavone is associated with a lower risk of lung adenocarcinoma among never smokers. Here, we examined the associations of isoflavone and soy food intake with lung cancer and its histologic types in never smokers. Methods: We performed a pooled analysis using data from the Japan Public Health Center-based Prospective Study, Shanghai Women's Health Study and Shanghai Men's Study with 147,296 never smokers aged 40–74 years with no history of cancer. During 1,990,040 person-years of follow-up, 1247 lung cancer cases were documented. Dietary isoflavone and soy food intake were assessed using a food-frequency questionnaire. Multivariable Cox proportional hazards models assessed the associations between isoflavone and soy intake with incidence of lung cancer by histologic type. Results: A higher intake of dietary isoflavone and soy food were associated with reduced risk of lung adenocarcinoma. The multivariable hazard ratios (HRs) (95% CI) of risk of lung adenocarcinoma for the highest versus lowest intakes of isoflavone and soy food were 0.74 (0.60–0.92) and 0.78 (0.63–0.96), respectively. The multivariable HRs of risk of lung adenocarcinoma associated with each 10 mg/day increase in isoflavone and each 50 g/day increase in soy food intake were 0.81 (0.70–0.94) and 0.84 (0.73–0.96), respectively. Conclusion: Higher intake of isoflavone and soy food was associated with lower risk of lung adenocarcinoma in never smokers. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the impact of fermented and unfermented soy intake, based on the following soy-derived products: tofu, soymilk, natto, and miso, on the risk of liver cancer among Japanese adults. Methods: 75,089 Participants of the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from the time of the 5-year follow-up questionnaire until the end of 2012–2013. Subjects with available data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infection status from blood samples (n = 14,016) and those who were anti-HCV antibody (anti-HCV) or hepatitis B virus antigen (HBsAg) positive (n = 1033) were also analyzed separately. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: During 1,145,453 person-years, 534 newly diagnosed cases of liver cancer were identified in the JPHC Study. For miso intake among men, the multivariate-adjusted highest versus lowest quartile HR was 0.65 (95% CI, 0.48–0.89); p for trend = 0.006. Results were similar in those who were anti-HCV or HBsAg positive, 0.24 (0.08–0.70); p for trend = 0.004 highest versus lowest tertile. For the sub-analysis among only participants with known hepatitis infection status and HCV and HBsAg adjustment, a similar association was observed. In the multivariate complete cohort analysis, among women, the highest intake of fried tofu was inversely associated with the risk of liver cancer, HR = 0.45 (0.26–0.80); p for trend = 0.014. Conclusions: We observed no association between total soy intake, fermented and unfermented, and risk of liver cancer, and only an inverse association between miso intake and liver cancer among men. [ABSTRACT FROM AUTHOR]

Smoking has been consistently associated with the risk of colorectal cancer (CRC) in Western populations; however, evidence is limited and inconsistent in Asian people. To assess the association of smoking status, smoking intensity and smoking cessation with colorectal risk in the Japanese population, we performed a pooled analysis of 10 population‐based cohort studies. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox's proportional hazards model and then pooled using a random‐effects model. Among 363 409 participants followed up for 2 666 004 person‐years, 9232 incident CRCs were identified. In men, compared with never smokers, ever smokers showed higher risk of CRC. The HRs (95% CI) were 1.19 (1.10‐1.29) for CRC, 1.19 (1.09‐1.30) for colon cancer, 1.28 (1.13‐1.46) for distal colon cancer and 1.21 (1.07‐1.36) for rectal cancer. Smoking was associated with risk of CRC in a dose‐response manner. In women, compared with never smokers, ever smokers showed increased risk of distal colon cancer (1.47 [1.19‐1.82]). There was no evidence of a significant gender difference in the association of smoking and CRC risk. Our results confirm that smoking is associated with an increased risk of CRC, both overall and subsites, in Japanese men and distal colon cancer in Japanese women. What's new? Colorectal cancer (CRC) has been included in lists of tobacco‐related cancers. However, this inclusion has been based on data from Western populations. Studies of Asian populations have yielded conflicting results. In the current study, the authors conducted a pooled analysis of 10 cohort studies in Japan. They found that smoking is also associated with an increased risk of CRC (both overall and at subsites) in Japanese men, and of distal colon cancer in Japanese women. This increase in risk was dose dependent. [ABSTRACT FROM AUTHOR]

Background: Although preclinical studies suggest that fermented soy foods may have a protective effect against breast cancer, no prospective cohort studies have examined this association. Objective: Our study examined the association between fermented and nonfermented soy food intake and breast cancer risk using a population‐based prospective cohort study in Japan. Methods: We included a total of 47,614 women aged 45–74 years in an analysis of the Japan Public Health Center‐based Prospective Study (JPHC Study). A validated food frequency questionnaire (FFQ) was used for the assessment of dietary intake. Breast cancer incidence was analyzed by multivariate Cox proportional hazards regression models. Results: During an average of 15.5 years of follow‐up, 825 breast cancer cases were newly identified. We found no association of intake of soy foods with breast cancer risk, regardless of fermentation, with multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest quartiles of fermented and nonfermented soy food intake of 0.94 (0.67, 1.32) and 1.15 (0.85, 1.57) compared with the lowest quartile (p for trend = 0.305 and 0.393). Unlike nonfermented soy, higher intake of fermented soy foods was associated with a significant decrease in the risk of nonlocalized breast cancer. The HR and 95% CI in the highest compared to lowest intake category of fermented soy foods was 0.53 (0.28, 0.99) versus nonfermented soy foods 0.85 (0.51, 1.42) (p for trend = 0.026 and 0.797). Conclusions: Our analyses showed that fermented soy foods had no association with overall breast cancer but may be associated with decreased risk of nonlocalized breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: We examined the association between meat intake and mortality due to all-cause and major causes of death using a population-based cohort study in Japan. Methods: 87,507 Japanese aged between 45 and 74 years old at 5-year follow-up study were followed for 14.0 years on average. Associations between meat intake and mortality risk were assessed using a Cox proportional hazards model. Results: A heavy intake of total meat was associated with a higher risk of all-cause mortality relative to the lowest quartile intake in men (Q4: HR,1.18; 95%CIs, 1.06–1.31). A higher intake of total meat was associated with a lower risk of stroke mortality in women (Q2: HR, 0.70; 95%CIs, 0.51–0.94, Q3: HR, 0.68; 95%CIs, 0.50–0.95, Q4: HR, 0.66; 95%CIs, 0.44–0.99). A heavy intake of red meat was also associated with all-cause mortality (Q4: HR, 1.13; 95%CIs, 1.02–1.26) and heart disease mortality (Q4: HR, 1.51; 95%CIs, 1.11–2.06) in men but not in women. Heavy intake of chicken was inversely associated with cancer mortality in men. Conclusions: Heavy intakes of total and red meat were associated with an increase in all-cause and heart disease mortality in men, while total meat intake was associated with a lower risk of stroke mortality in women. [ABSTRACT FROM AUTHOR]

Background: Soy is commonly consumed in east Asian countries and is suggested to reduce colorectal cancer (CRC) risk. However, results from epidemiologic studies are inconsistent, despite the anti-inflammatory and antiproliferative properties of soy isoflavones and soy protein.Objective: We evaluated the association between soy isoflavones and soy protein and CRC risk using 4 prospective cohort studies from China and Japan.Methods: Data were pooled from the Shanghai Women's Health Study (SWHS), Shanghai Men's Health Study (SMHS), Japan Public Health Center-based Prospective Study Cohort 1 (JPHC1), and Cohort 2 (JPHC2). Cox proportional hazards models estimated HRs and corresponding 95% CIs for the association of soy protein and isoflavone intake with CRC risk. The study included 205,060 individuals, among whom 2971 were diagnosed with incident CRC over an average follow-up of 12.7 y.Results: No statistically significant associations with CRC risk were observed for soy protein or isoflavone intake. No association was observed among ever smokers consuming higher isoflavones (HRisoflavones: 0.83; 95% CI: 0.68, 1.00) and soy protein (HRsoy protein: 0.81; 95% CI: 0.39, 1.10). However, risk reductions were observed among premenopausal women with a body mass index [BMI (kg/m2)] <23.0 at baseline for higher isoflavone (HRisoflavones: 0.58, 95% CI: 0.34, 0.98).Conclusions: No evidence for an overall reduction in CRC risk by increasing soy food intake (i.e., protein or isoflavones) was observed. However, the association between soy and CRC risk may vary by BMI, smoking, and menopausal status among women. Future investigations are needed to further understand the biologic mechanisms observed. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype of esophageal cancer worldwide. Measurements of circulating inflammation‐related biomarkers may inform etiology or provide noninvasive signatures for early diagnosis. We therefore examined levels of inflammation molecules for associations with ESCC risk. Using a case–cohort study designed within the Japan Public Health Center‐based Prospective Study, we measured baseline plasma levels of 92 biomarkers using a multiplex assay in a subcohort of 410 randomly selected participants and 66 participants with incident ESCC (including four cases that occurred in the subcohort). ESCC hazard ratios (HRs) were calculated for 2–4 quantiles of each biomarker by Cox proportional hazards regression models with age as the time metric, adjusted for sex, smoking and alcohol use. Twenty analytes were undetectable in nearly all samples. Of the remaining 72, 12 biomarkers (FGF19, ST1A1, STAMBP, AXIN1, CASP8, NT3, CD6, CDCP1, CD5, SLAMF1, OPG and CSF1) were associated with increased ESCC risk (ptrend < 0.05) with HRs per quantile 1.28–1.65. Seven biomarkers (CXCL6, CCL23, CXCL5, TGFA, CXCL1, OSM and CCL4) were inversely associated with HRs 0.57–0.72. FGF19, CASP8, STAMBP, ST1A1 and CCL‐4 met statistical significance with false discovery rate correction. Associations did not differ <5 vs. ≥5 years between blood collection and ESCC diagnosis. CASP8, STAMBP and ST1A1 were strongly correlated (p < 0.05). Our study expands the range of inflammation molecules associated with the development of this highly lethal neoplasia. Correlations among these novel biomarkers suggest a possible shared pathway. These findings need replication and could further delineate ESCCs molecular mechanisms of carcinogenesis. What's new?: Chronic inflammation has long been considered an important contributor to carcinogenesis. Circulating levels of inflammation‐related biomarkers may thus provide valuable information regarding cancer etiology, and may eventually aid in the early diagnosis of some cancers. In this study, the authors identified five such proteins that are associated with esophageal squamous cell carcinoma (ESCC) risk. These biomarkers may improve our understanding of ESCC etiology, enhance non‐invasive, molecular diagnostic panels, and may provide potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population‐based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self‐administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable‐adjusted Cox proportional hazards regression models. During 1,802,581 person‐years of follow‐up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07–1.15]), esophagus (2.11 [1.00–4.45]), stomach (1.36 [1.19–1.55]), liver (1.69 [1.10–2.61]), pancreas (2.63 [1.45–4.79]), lung (1.51 [1.14–2.00]), uterus (1.93 [1.06–3.51]) and bladder cancers (6.06 [2.49–14.74]) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high‐risk of those cancers. What's new? Although many epidemiological studies have reported an association between family history of cancer and concordant cancer risk, the association has not been evaluated in a comprehensive prospective study with adjustment for lifestyle habits. We found that a family history of cancer is associated with increased risk in the incidence of several concordant cancers in an Asian population. [ABSTRACT FROM AUTHOR]

Background/objectives: Eating a variety of foods has been recommended in the dietary guidelines of many developed nations, as well as global dietary guidelines. We investigated the potential effect of dietary diversity on the risk of total mortality and major causes of mortality in a large-scale cohort study involving the Japanese population.Subjects/methods: From 1995 to 2012, 79,904 participants (37,240 men and 42,664 women) aged 45 to 74 years, without histories of ischemic heart disease, stroke, or cancer were followed-up for a median of 14.9 years. We used 133 food and beverage items listed on a 5-year follow-up food frequency questionnaire, and the daily frequency of consumption for each item (excluding five alcoholic beverages) was counted. Multivariable-adjusted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to compare the highest and lowest quintiles.Results: An inverse association was identified between total dietary diversity and mortality rates in women (highest quintile HR: 0.81; 95% CI: 0.71, 0.92; p for trend = 0.002) but the same trend was not observed in men (highest quintile HR: 0.96; 95% CI: 0.87, 1.10; p for trend = 0.266). In addition, fruit diversity was associated with lower mortality rates in men (highest quintile HR: 0.87; 95% CI: 0.79, 0.95; p for trend = 0.006), whereas soy diversity was associated with lower mortality rates in women (highest quintile HR: 0.89; 95% CI: 0.79, 1.00; p for trend = 0.004). With regard to men, meat and fish diversity were associated with higher mortality rates (highest quintiles of meat and fish diversity HR: 1.15 [95% CI: 1.06, 1.25] and 1.12 [95% CI: 1.02, 1.22], respectively).Conclusions: These findings indicate that consuming a greater diversity of total foods and increasing the diversity of fruit and soy consumed have considerable public health implications. [ABSTRACT FROM AUTHOR]

Background: Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse.Objective: We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan.Methods: We studied 82,330 participants (38,663 men; 43,667 women) aged 45-74 y without a past history of cancer. Participants were asked to respond to a validated questionnaire that included 138 food items. The association between cruciferous vegetable intake and lung cancer incidence was assessed with the use of Cox proportional hazard regression analysis to estimate HRs and 95% CIs (with adjustments for potential confounding factors).Results: After 14.9 y of follow-up, a total of 1499 participants (1087 men; 412 women) were diagnosed with lung cancer. After deleting early-diagnosed cancer and adjusting for confounding factors, we observed a nonsignificant inverse trend between cruciferous vegetable intake and lung cancer risk in men in the highest compared with the lowest quartiles (multivariate HR: 0.85; 95% CI: 0.69, 1.06; P-trend = 0.13). Stratified analysis by smoking status revealed a significant inverse association between cruciferous vegetable intake and lung cancer risk among those who were never smokers and those who were past smokers after deleting lung cancer cases in the first 3 y of follow-up [multivariate HR for never smokers: 0.49 (95% CI: 0.27, 0.87; P-trend = 0.04); multivariate HR for past smokers: 0.59 (95% CI: 0.35, 0.99; P-trend = 0.10)]. No association was noted in men who were current smokers and women who were never smokers.Conclusion: This study suggests that cruciferous vegetable intake may be associated with a reduction in lung cancer risk among men who are currently nonsmokers. [ABSTRACT FROM AUTHOR]

Objective: A meta-analysis showed an inverse association of a prudent/healthy dietary pattern with all-cause mortality and no association of a western/unhealthy dietary pattern. However, the association of distinctive dietary patterns of Japanese population with mortality remains unclear. We prospectively investigated the association between dietary patterns and all-cause, cancer, and cardiovascular disease mortality among Japanese adults. Methods: Participants were 36,737 men and 44,983 women aged 45–74 years who participated in the second survey of the Japan Public Health Center-based Prospective Study (1995–1998) and who had no history of serious disease. Dietary patterns were derived from principal component analysis of the consumption of 134 food and beverage items ascertained by a food frequency questionnaire. Hazard ratios of death from the second survey to December 2012 were estimated using cox proportional hazard regression analysis. Results: A prudent dietary pattern, which was characterized by high intake of vegetables, fruit, soy products, potatoes, seaweed, mushrooms, and fish, was significantly associated with decreased risk of all-cause and cardiovascular disease mortality. The multivariable-adjusted hazard ratios (95% confidence intervals) of all-cause and cardiovascular disease mortality for the highest versus lowest quartile of the prudent dietary pattern score were 0.82 (0.77 to 0.86) and 0.72 (0.64 to 0.79), respectively (P for trend <0.001 in both). A Westernized dietary pattern, characterized by high intake of meat, processed meat, bread, and dairy products, was also inversely associated with risk of all-cause, cancer, and cardiovascular disease mortality. A traditional Japanese dietary pattern was not associated with these risks. Conclusions: The prudent and Westernized dietary patterns were associated with a decreased risk of all-cause and cardiovascular disease mortality in Japanese adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study aimed to add to prospective data on the possible inverse association between coffee consumption and endometrial cancer risk, already supported by several case-control studies. Coffee and tea consumption and possible confounding factors were assessed among 42,270 women aged 30–49 years at enrollment in 1991–1992 in the Swedish Women's Lifestyle and Health cohort study, with complete follow-up through 2009. We calculated caffeine intake per day; Cox proportional hazard models were used to estimate multivariable relative risks (mRR) for endometrial cancer with 95% confidence intervals (CIs). One hundred forty-four endometrial cancers were diagnosed during follow-up. Women with and without endometrial cancer had a similar mean daily coffee consumption (549 vs. 547 g), tea consumption (104 vs. 115 g), and caffeine intake (405 vs. 406 mg). Compared to those consuming <2 cups of coffee per day, women consuming >3 cups had a mRR of 1.56 (95% CI: 0.94–2.59;Pfor trend = 0.17). Compared with the lowest tertile of caffeine intake, the highest tertile had a mRR of 1.32 (95% CI: 0.87–1.99;Pfor trend = 0.27). Our study provides no convincing evidence of an association between coffee consumption, tea consumption, or caffeine intake and endometrial cancer risk among middle-aged women. [ABSTRACT FROM PUBLISHER]

Background: Food sources and intakes of zinc and heme iron may differ between Western and Asian populations. However, all of the studies on the association between zinc and heme iron intakes and colorectal cancer have been conducted in Western populations. Objective: We investigated the association between zinc and heme iron intakes and colorectal cancer risk in a Japanese general population. Design: We conducted a large, population-based prospective study in 39,721 men and 45,376 women aged 45-74 y. Heme iron and zinc intakes were measured by using a validated food-frequency questionnaire in either 1995 or 1998. Results: During as many as 808,053 person-years of follow-up until the end of 2006, 1284 colorectal cancer cases were identified. In multivariate-adjusted models, zinc and heme iron intakes were not associated with colorectal cancer in either men or women. In comparison with the lowest quartile, the HRs (95% CIs) for developing colorectal cancer in the fourth quartile of zinc and heme iron intakes were 0.77 (0.58, 1.03; P-trend = 0.2) and 1.06 (0.79, 1.42; P-trend = 0.6), respectively, for men and 1.05 (0.77, 1.44; /"-trend = 0.4) and 0.88 (0.61, 1.29; F-trend = 0.4), respectively, for women. Conclusion: Our results in a Japanese population with lower intakes and different major food sources of zinc and heme iron in comparison with those of Western populations suggest that zinc and heme iron intakes are not associated with colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: Although height and body mass index (BMI) are reported to be positively associated with several common cancers, evidence regarding their association with brain tumor risk remains sparse, particularly in Asian populations. In this study, we analyzed the association between height and BMI and brain tumor risk in a Japanese population using a large population-based prospective cohort study.Methods: A total of 102,925 participants (48,213 men and 54,712 women) enrolled in the Japan Public Health Center-based Prospective Study were followed from baseline, namely 1990 for cohort I and 1993 for cohort II, until 2012. Information on participants' dietary and lifestyle habits, including height and body weight, was collected through survey questionnaires administered at baseline. We used the Cox proportional hazards regression model to estimate hazard ratios and 95% confidence intervals (CIs) for brain tumor incidence, with adjustment for potential confounding variables.Results: During an average follow-up of 18.1 years, 157 (70 men and 87 women) cases of brain tumor were newly diagnosed. BMI showed a statistically insignificant positive association with the risk of brain tumor. In addition, statistically significant positive trends were seen for men and meningioma, with multivariable-adjusted hazard ratios for a BMI of 27.5 to less than 40 versus 18.5 to less than 23 kg per m2 of 2.14 (95% CI = 0.99-4.59) (P = 0.03) and 1.98 (95% CI = 0.84-4.67) (P = 0.046), respectively. In contrast, height showed no clear association with brain tumor risk, overall or in subgroup analysis.Conclusions: Compared with a BMI of 18 to less than 23.5 kg per m2, a higher BMI was associated with higher risk of brain tumor, particularly in men and with meningioma. [ABSTRACT FROM AUTHOR]

Gastric cancer is preceded by a chronic inflammatory process. Circulating levels of inflammation-related markers may reveal molecular pathways contributing to cancer development. Our study evaluated risk associations of gastric cancer with a wide range of systemic soluble inflammation and immune-response proteins. We performed a case-cohort analysis within the JPHC Study II, including a subcohort of 410 participants selected randomly within defined age and sex groups, and 414 individuals with incident gastric cancer. Ninety-two biomarkers were measured in baseline plasma using proximity extension assays. Gastric cancer multivariable hazard ratios were calculated for two to four quantiles used as ordinal variables of each biomarker by Cox proportional hazards regression models with age as the time metric. Of 73 evaluable biomarkers, three (CCL11, CCL20 and IL17C) were associated with increased gastric cancer risk and two (CCL23 and MMP1) with reduced cancer risk (P trends < 0.05). However, no association was statistically significant after a false discovery rate correction. This study largely expands the range of inflammation molecules evaluated for gastric cancer risk but failed to identify novel associations with this neoplasia. [ABSTRACT FROM AUTHOR]

Alcohol drinking is a risk factor for cancer. The degree of risk is increased in subjects showing the flushing response, which is due to aldehyde dehydrogenase 2 (ALDH2) polymorphism. The attributable risk of alcohol drinking for cancer in Japan has not been sufficiently investigated with consideration of flushing response. We followed 78,825 Japanese in JPHC study cohort II. The association between alcohol consumption and cancer incidence was assessed according to self-reported flushing response using Cox proportional hazards regression models. The population-attributable fraction (PAF) of cancer incidence was also estimated. During 1993-2013 (average follow-up, 16.8 years), 8486 incident cancers (included 4386 alcohol-related cancers) were reported. Half of men and 36% of women had flushing response. In men with flushing response, moderate or higher alcohol drinking increased the risk of alcohol-related cancers compared with non-drinkers (150-299 g/week, HR 1.63, 95% CI, 1.43-1.99; 300-449 g/week, HR 2.02 95% CI, 1.67-2.44; ≥450 g/week, HR 1.75, 95% CI, 1.39-2.21). When flushing response was considered in comparisons between non-drinkers and non-flushers, non-flushing heavy drinkers had a slightly higher PAF than flushers (all cancers: flushers, 2.0% and non-flushers, 2.2%; alcohol-related cancers: flushers, 3.8% and non-flushers, 5.8%). Although the risk of alcohol-related cancer in men with flushing response increased with increasing alcohol consumption, heavy drinkers were also at high risk regardless of flushing response. Considering the PAF of alcohol consumption on cancer, efforts to discourage heavy alcohol consumption to reduce the incidence of alcohol-related cancers appear warranted regardless of flushing response. [ABSTRACT FROM AUTHOR]