Publications by authors named "Manami Inoue"

472 Publications

Body Mass Index, Height, Weight Change, and Subsequent Lung Cancer Risk: The Japan Public Health Center-Based Prospective Study.

Cancer Epidemiol Biomarkers Prev 2021 Jun 25. Epub 2021 Jun 25.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan.

Background: Body mass index (BMI) is inversely associated with lung cancer risk, while residual confounding by smoking or weight change is controversial. Evidence on height and lung cancer is scarce.

Methods: We investigated the associations between anthropometrics, BMI, and height, and incidence of lung cancer among 92,098 study subjects (44,158 men and 47,940 women) in the Japan Public Health Center-based Prospective Study. Cox proportional hazards regression was performed with adjustment for potential confounders and by cancer subtypes and smoking status. Information on weight and height was self-reported at baseline, and validated using measured health check-up data.

Results: During follow-up between 1990 and 2013 (average, 19.1 years), a total of 2,152 lung cancer cases were newly diagnosed. In a multivariate regression model, lower BMI was positively associated with overall lung cancer risk [<19 kg/m HR = 1.48; 95% confidence interval (CI) = 1.18-1.85 and 19-22.9 kg/m; HR = 1.19; 95% CI = 1.05-1.35; = <0.001] in men. The risk estimate was also elevated for adenocarcinoma in the BMI <19 kg/m category and for squamous cell carcinoma among men in the 19-22.9 kg/m BMI category. An association was also observed between low BMI, weight decrease, and squamous cell carcinoma in women. No significant associations were observed for other weight categories, height, weight change and lung cancer, adenocarcinoma, squamous and small cell carcinoma.

Conclusions: Our prospective study suggests that lower BMI may be associated with an increased risk of smoking-related lung cancer in Japan, irrespective of gender.

Impact: This study highlights the association between lower BMI and the risk of lung cancer in men.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0195DOI Listing
June 2021

Dietary glycemic index, glycemic load and mortality: Japan Public Health Center-based prospective study.

Eur J Nutr 2021 Jun 22. Epub 2021 Jun 22.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Purpose: Long-term associations of dietary glycemic index (GI) and glycemic load (GL) with mortality outcomes remain unclear.

Methods: The present analysis included 72,783 participants of the Japan Public Health Center-based Prospective Study. Participants who responded to the 5-year follow-up questionnaire in 1995-1999 were followed-up until December 2015. We estimated the risk of total and cause-specific mortality associated with GI and GL using Cox proportional hazards regression models.

Results: During 1,244,553 person years of follow-up, 7535 men and 4913 women died. GI was positively associated with all-cause mortality. As compared with the lowest quartile, the multivariable HR for those who had the highest quartile of GI was 1.14 (95% CI 1.08-1.20). The HRs for death comparing the highest with the lowest quartile were 1.28 (95% CI 1.14-1.42) for circulatory system diseases, 1.33 (95% CI 1.14-1.55) for heart disease, 1.32 (95% CI 1.11-1.57) for cerebrovascular disease, and 1.45 (95% CI 1.18-1.78) for respiratory diseases. GI was not associated with mortality risks of cancer and digestive diseases. GL showed a null association with all-cause mortality (highest vs lowest quartile; HR 1.04; 95% CI 0.96-1.12). However, among those who had the highest quartile of GL, the HRs for death from circulatory system diseases was 1.24 (95% CI 1.05-1.46), cerebrovascular disease was 1.34 (95% CI 1.03-1.74), and respiratory diseases was 1.35 (95% CI 1.00-1.82), as compared with the lowest quartile.

Conclusion: In this large prospective cohort study, dietary GI and GL were associated with mortality risks.
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http://dx.doi.org/10.1007/s00394-021-02621-0DOI Listing
June 2021

Effectiveness of screening using fecal occult blood test and colonoscopy on the risk of colorectal cancer: The Japan Public Health Center-based Prospective Study.

J Epidemiol 2021 May 29. Epub 2021 May 29.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center.

Background: Few cohort studies have used multiple surveys of screening attendance to simultaneously evaluate the effectiveness of fecal occult blood test (FOBT) and colonoscopy.

Methods: We analyzed data of 30,381 middle-aged Japanese adults from a population-based prospective cohort study. Information on FOBT and colonoscopy was obtained from three questionnaire surveys (every 5 years). We classified the subjects into three groups-the FOBT (15,649 subjects), screening colonoscopy (2,407 subjects), and unscreened (12,325 subjects) groups. We used the unscreened group as reference group to compare the mortality and incidence of colorectal cancer (CRC).

Results: During the 14-year follow-up, 64, 12, and 104 CRC deaths were identified in the FOBT, screening colonoscopy, and unscreened groups, respectively. The risk of CRC death reduced with increasing the number of FOBTs (p for trend=0.02) and reduced by 44% in the subjects screened twice or thrice using FOBT (HR=0.56 95% CI, 0.33-0.94). Significant decreases were seen for the incidence of CRC, but not seen for the incidence of non-advanced CRC in the FOBT group. Concerning the screening colonoscopy, subjects screened at the start of follow-up showed a 69% reduced risk of CRC death (HR=0.31, 95% CI, 0.10-0.9996). Significant decreases were also seen for the incidence of CRC and non-advanced CRC in the subjects screened at the start of follow-up.

Conclusion: FOBT, depending on the number of FOBTs, and colonoscopy, depending on recency, reduced the risk of death due to CRC and the incidence of CRC.
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http://dx.doi.org/10.2188/jea.JE20210057DOI Listing
May 2021

Public Health Interventions for Gastric Cancer Control.

Authors:
Manami Inoue

Gastrointest Endosc Clin N Am 2021 Jul;31(3):441-449

Division of Prevention, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address:

Despite its generally decreasing trend in incidence, gastric cancer remains the fifth-most common cancer worldwide. Gastric cancer has substantially declined over the past century, thanks to decreases in risk factors such as Helicobacter pylori infection, tobacco smoking, and salt-preserved food intake. These decreases have resulted from natural interventions and population-based intervention strategies. H pylori eradication for infected patients has potential as a prevention strategy for those at high risk, but warrants a longer follow-up period. The ongoing increase in obesity prevalence may cause an increase in cardia gastric cancer, especially in Western populations, and should be carefully monitored.
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http://dx.doi.org/10.1016/j.giec.2021.03.002DOI Listing
July 2021

Dietary glycemic index, glycemic load, and endometrial cancer risk: The Japan Public Health Center-based Prospective Study.

Cancer Sci 2021 May 30. Epub 2021 May 30.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Evidence supporting the association of glycemic index (GI) and glycemic load (GL) with the risk of endometrial cancer is controversial and reports from Asia were limited. Therefore, we aimed to investigate the association in Japanese women. We evaluated 52 460 women in the Japan Public Health Center-based Prospective Study aged 45-74 years who responded to the 5-year follow-up survey. GI and GL were calculated from a validated food frequency questionnaire, and the participants were divided into three groups by GI and GL. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with the Cox proportional hazard model adjusted for potential confounding factors. As a result, within 15.5 years of follow-up, 166 new cases of endometrial cancer were identified. Compared with the lowest GI and GL tertile groups, the HR of the risk of endometrial cancer in the highest GI tertile group was 0.80 (95% CI, 0.53-1.20; P  = .33), and that of the highest GL tertile group was 0.79 (95% CI, 0.52-1.19; P  = .82). The results were unchanged after stratification by body mass index, coffee consumption, and history of diabetes. In conclusion, we did not find any significant association between GI and GL with the risk of endometrial cancer. Further research is required to clarify the association.
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http://dx.doi.org/10.1111/cas.14997DOI Listing
May 2021

Reduction in total and major cause-specific mortality from tobacco smoking cessation: a pooled analysis of 16 population-based cohort studies in Asia.

Int J Epidemiol 2021 Feb 5. Epub 2021 Feb 5.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Little is known about the time course of mortality reduction following smoking cessation in Asians who have smoking behaviours distinct from their Western counterparts. We evaluated the level of reduction in all-cause, cardiovascular disease (CVD) and lung cancer mortality by years since quitting smoking, in Asia.

Methods: Using Cox regression, we analysed individual participant data (n = 709 151) from 16 prospective cohorts conducted in China, Japan, Korea/Singapore, and India/Bangladesh, separately by cohorts. Cohort-specific hazard ratios (HRs) were combined using a random-effects meta-analysis.

Results: During a mean follow-up of 12.0 years, 108 287 deaths were ascertained-35 658 from CVD and 7546 from lung cancer. Among Asian men, a dose-response relationship of risk reduction in deaths from all causes, CVD and lung cancer was observed with an increase in years after smoking cessation. Compared with never smokers, however, all-cause and CVD mortality among former smokers remained elevated 10-14 years after quitting [multivariable-adjusted HR (95% confidence interval (CI) = 1.25 (1.13-1.37) and 1.20 (1.02-1.41), respectively]. Lung cancer mortality stayed almost 2-fold higher than among never smokers 15-19 years after smoking cessation [1.97 (1.41-2.73)], particularly among former heavy smokers [2.62 (1.71-4.00)]. Women who quitted for ≥5 years retained a significantly elevated mortality from all causes, CVD and lung cancer. Overall patterns of the cessation-mortality associations were similar across countries.

Conclusions: Our findings suggest that adverse effects of tobacco smoking persist for an extended time period, even for more than two decades, which is beyond the time windows defined in current clinical guidelines for risk assessment of lung cancer and CVD.
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http://dx.doi.org/10.1093/ije/dyab087DOI Listing
February 2021

Prediagnostic circulating inflammation-related biomarkers and gastric cancer: A case-cohort study in Japan.

Cytokine 2021 Aug 10;144:155558. Epub 2021 May 10.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

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 < 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.
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http://dx.doi.org/10.1016/j.cyto.2021.155558DOI Listing
August 2021

Long-term response of Helicobacter pylori antibody titer after eradication treatment in middle-aged Japanese: JPHC-NEXT Study.

J Epidemiol 2021 Apr 28. Epub 2021 Apr 28.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center.

Background: Helicobacter pylori (H. pylori) is an established causative factor of gastric cancer. Although the expansion of insurance coverage has led to an increase in the number of patients treated for H. pylori, the population impact of eradication treatment for H.pylori has been scarcely investigated. This study aimed to clarify the long-term responses of H. pylori antibody titer after eradication treatment using large scale cross-sectional data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study).

Methods: A total of 55,282 Japanese participants aged 40 to 74 years residing in 16 areas provided blood samples between 2011 and 2016. From these, treated (n=6,276) and untreated subjects who were seropositive for H. pylori or had serological atrophy (n= 22,420) formed the study population (n=28,696). Seropositivity was defined as an anti-H. pylori IgG titer of ≥10 U/mL. Antibody level was compared among subjects according to self-reported treatment history as untreated, and treated for less than one year (<1Y), one to five years (1-5Y), and more than six years ago (6Y+).

Results: Median serum antibody titer was 34.0 U/mL, 7.9 U/mL, 4.0 U/mL, and 2.9 U/mL for the Untreated, <1Y, 1-5Y, and 6Y+ groups, respectively. While those treated for H.pylori within the previous year had a 76.8% lower antibody titer compared to untreated subjects, approximately 41% of subjects were still seropositive.

Conclusions: A significant reduction in H.pylori antibody titer occurs within one year after eradication treatment, but that a long period is needed to achieve complete negative conversion.
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http://dx.doi.org/10.2188/jea.JE20200618DOI Listing
April 2021

Dietary Inflammatory Index Is Associated With Inflammation in Japanese Men.

Front Nutr 2021 9;8:604296. Epub 2021 Apr 9.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Dietary components are known to affect chronic low-grade inflammation status. The dietary inflammatory index (DII®) was developed to measure the potential impact of a diet on an individual's inflammatory status, and it has been validated mainly in Western countries. This study aimed to examine the validity of the energy-adjusted DII (E-DII) using high-sensitivity C-reactive protein (hs-CRP) concentration in Japanese men and women. In total, 6,474 volunteers from a cancer-screening program (3,825 men and 2,649 women) completed a food frequency questionnaire (FFQ) and their hs-CRP concentrations were evaluated. E-DII scores were calculated on the basis of 30 food parameters derived from the FFQ. Higher E-DII scores reflect a greater pro-inflammatory potential of the diet. The associations between E-DII quartiles and hs-CRP concentration were assessed using regression models adjusted for age, body mass index, smoking status, and amount of physical activity. Mean E-DII in men and women was + 0.62 ± 1.93 and -1.01 ± 2.25, respectively. The proportion of men and women who had hs-CRP concentration >3 mg/L was 4.7 and 3.1%, respectively. A significant positive association was observed between E-DII score and hs-CRP concentration in men; geometric mean of hs-CRP concentration in the lowest and highest E-DII quartiles was 0.56 mg/L and 0.67 mg/L ( < 0.01), respectively. The odds ratio (95% confidence interval) of having an elevated hs-CRP concentration (>3 mg/L) was 1.72 (1.10-2.67) in the highest E-DII quartile ( = 0.03) in men. However, no association was observed between E-DII score and hs-CRP concentration in women, except in those not taking prescription medications. DII was associated with inflammation status in Japanese men, but the association was limited in Japanese women.
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http://dx.doi.org/10.3389/fnut.2021.604296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062774PMC
April 2021

Effects of Helicobacter pylori eradication on gastric cancer incidence in the Japanese population: a systematic evidence review.

Jpn J Clin Oncol 2021 Jul;51(7):1158-1170

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: In Japan, there are ongoing efforts to shift the gastric cancer prevention and control policy priorities from barium-based screening to Helicobacter pylori (H. pylori)-oriented primary prevention. A comprehensive summary of the evidence regarding the effects of H. pylori eradication on the risk of gastric cancer could inform policy decisions.

Methods: We conducted a systematic review and meta-analysis of published studies evaluating the effectiveness of H. pylori eradication for the prevention of gastric cancer in otherwise healthy individuals (primary prevention) and early gastric cancer patients (tertiary prevention).

Results: In total, 19 studies were included. Three moderate-quality observational cohort studies showed that H. pylori eradication may be associated with a decreased risk of gastric cancer in healthy asymptomatic Japanese people. There is moderate certainty regarding the effectiveness of H. pylori eradication in patients with gastrointestinal diseases, such as peptic ulcers. A meta-analysis of 10 observational studies with otherwise healthy individuals (mainly peptic ulcer patients) yielded an overall odds ratio of 0.34 (95% CI: 0.25-0.46). Regarding tertiary prevention, the overall odds ratio for developing metachronous gastric cancer was 0.42 (95% CI: 0.35-0.51) in the eradication group in a meta-analysis of nine studies involving early gastric cancer patients who underwent endoscopic resection.

Conclusion: H. pylori eradication is effective in preventing gastric cancer in the Japanese population, regardless of symptoms. Well-designed, large cohort studies are warranted to determine the long-term efficacy and safety of H. pylori eradication in the context of reducing the gastric cancer burden through population-based screening and treatment.
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http://dx.doi.org/10.1093/jjco/hyab055DOI Listing
July 2021

Association of sugary drink consumption with all-cause and cause-specific mortality: the Japan Public Health Center-based Prospective Study.

Prev Med 2021 07 15;148:106561. Epub 2021 Apr 15.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: Few epidemiologic studies have assessed the associations of sugary drink consumption with mortality outcomes among Asian populations.

Methods: This study included 70,486 participants in the Japan Public Health Center-based Prospective Study at the age of 45-74 years in 1995-1999. A validated food frequency questionnaire was used to assess the consumption of sugary drinks. We estimated the risk of total and cause-specific mortality associated with sugary drink consumption using Cox proportional hazards regression model.

Results: Mean follow-up was 17.1 years, during which 11,811 deaths were documented. Sugary drink consumption was associated with higher total mortality, with multivariate HR of 1.06 (95% CI 1.00-1.13) for quintile 3, 1.07 (95% CI 1.01-1.13) for quintile 4, and 1.15 (95% CI 1.09-1.22) for quintile 5, compared with quintile 1 (P < 0.001 for trend). Additionally, positive associations with cause-specific mortality were observed, including death from circulatory system diseases (quintile 5 vs quintile 1; HR, 1.23; 95% CI 1.09-1.38) and heart disease (quintile 5 vs quintile 1; HR, 1.35; 95% CI 1.14-1.60).

Conclusion: In this large Japanese prospective study, sugary drink consumption was associated with all-cause and cause-specific mortality.
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http://dx.doi.org/10.1016/j.ypmed.2021.106561DOI Listing
July 2021

Association Between Birth Weight and Risk of Pregnancy-Induced Hypertension and Gestational Diabetes in Japanese Women: JPHC-NEXT Study.

J Epidemiol 2021 Apr 13. Epub 2021 Apr 13.

Epidemiology and Prevention Group, Center for Public Health and Sciences, National Cancer Center.

Background: Although prevalence of low birth weight has increased in the last 3 decades in Japan, no studies in Japanese women have investigated whether birth weight is associated with the risk of pregnancy complications, such as pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM).

Methods: We used data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT), a population-based cohort study in Japan that launched in 2011. In the main analysis, we included 46,365 women who had been pregnant at least once, for whom information on birth weight and events during their pregnancy was obtained using a self-administered questionnaire. Women were divided into five categories according to their birth weight, and the relationship between birth weight and risk of PIH and GDM was examined using multilevel logistic regression analyses with place of residence as a random effect.

Results: Compared to women born with birth weight of 3,000-3,999 grams, the risk of PIH was significantly higher among women born <1,500 grams (adjusted odd ratio [aOR] 1.60; 95% confidence interval [CI], 1.17-2.21), 1,500-2,499 grams (aOR 1.16; 95% CI, 1.03-1.30), and 2,500-2,999 grams (aOR 1.13; 95% CI, 1.04-1.22). The risk of GDM was significantly higher among women born 1,500-2,499 grams (aOR 1.20; 95% CI, 1.02-1.42), albeit non-significant association among women in other birthweight categories.

Conclusions: We observed an increased risk of PIH among women born with lower birth weight albeit non-significant increased risk of GDM among Japanese women.
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http://dx.doi.org/10.2188/jea.JE20200302DOI Listing
April 2021

Relationship between unhealthy sleep status and dry eye symptoms in a Japanese population: The JPHC-NEXT study.

Ocul Surf 2021 Apr 17. Epub 2021 Apr 17.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Purpose: To investigate whether and how unhealthy sleep habits (i.e., the frequency of difficulty falling or staying asleep, and the frequency of waking up tired) and the duration of sleep are related to the prevalence of dry eye disease (DED) in a general population.

Methods: This study included a total of 106,282 subjects aged 40-74 years who participated in a baseline survey of the Japan Public Health Center-based Prospective Study for the Next Generation. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Multivariable-adjusted logistic regression models were used to assess the relationships of various components of sleep status with DED.

Results: Higher frequencies of having difficulty falling or staying asleep, and waking up tired were significantly related to increased DED in both sexes (P<0.001). Compared with those with 8 h/day of sleep, shorter sleepers had an increased prevalence of DED in both sexes, although DED was increased among men who slept ≥10 h/day. By comparing participants with the greatest vs. the least difficulty of falling asleep, the multivariable-adjusted odds ratios (95% confidence interval [CI]) were 2.23 (95% CI, 1.99-2.49) for men and 1.91 (95% CI, 1.76-2.07) for women. When analyzed separately, the magnitude of each relationship was stronger with severe DED symptoms than with clinically diagnosed DED.

Conclusions: Sleep deprivation and poor sleep quality were significantly related to DED in a Japanese population.
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http://dx.doi.org/10.1016/j.jtos.2021.04.001DOI Listing
April 2021

Immune-related adverse events with immune checkpoint inhibitors: Special reference to the effects on the lungs.

Medicine (Baltimore) 2021 Apr;100(14):e25275

Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.

Abstract: Immune checkpoint inhibitors (ICIs) have emerged as evolutionary treatments for malignant diseases. Although ICIs can cause immune-related adverse events (irAEs) in various organs, precise timing after ICI initiation has been scarcely reported. Elucidating the effects of irAEs, such as time to onset, involvement of major organs, influence on progression-free survival (PFS), and overall survival (OS), are critical issues for physicians. Furthermore, lung-irAE as a whole is not well known.We conducted a retrospective study of 156 patients who were treated with ICIs and compared 82 irAE patients with 74 non-irAE patients.This study clearly demonstrated that the preferred period after induction of ICIs was significantly longer in lung-irAE than in other major organs (skin, digestive tract, and endocrine). The effect of irAEs on PFS and OS was evident PFS in the irAE group (n = 82) (median 128 days, interquartile range [IQR] 62-269 days, P = .002) was significantly longer than that in the non-irAE group (n = 74) (median 53 days, IQR 33-151 days). Similarly, OS was significantly longer in the irAE group (median 578 days, IQR 274-1027 days, P = .007) than in the non-irAE group (median 464 days, IQR: 209-842 days). However, this positive effect of irAEs in the lungs was not proportional to the extent of severity.Lung-irAEs can occur at a later phase than non-lung-irAEs and seemed not to prolong OS and PFS. However, further studies are needed to support these findings.
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http://dx.doi.org/10.1097/MD.0000000000025275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036099PMC
April 2021

Reproductive Factors and Lung Cancer Risk among Never-Smoking Japanese Women with 21 Years of Follow-Up: A Cohort Study.

Cancer Epidemiol Biomarkers Prev 2021 Jun 7;30(6):1185-1192. Epub 2021 Apr 7.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: Previous studies have reported inconsistent associations between reproductive factors and lung cancer.

Methods: We used data from the Japan Public Health Center-based Prospective Study, which included 400 incident lung cancer cases (305 adenocarcinoma) among 42,615 never-smoking women followed for a median of 21 years, to examine the associations of reproductive and hormonal factors with lung cancer by histological type using Cox proportional hazards models.

Results: Longer fertility span (≥36 years vs. ≤32 years) was associated with increased risk of lung adenocarcinoma (HR, 1.48; 95% CI, 1.07-2.06, = 0.01) but not with all lung cancer or nonadenocarcinoma. Similarly, late age at menopause (≥ 50 years) was associated with increased adenocarcinoma risk (vs. ≤ 47 years, HR, 1.41; 95% CI, 1.01-1.96, 0.04). Compared with premenopausal women, women with natural menopause (HR, 1.99; 95% CI, 1.02-3.88) or surgical menopause (HR, 2.75; 95% CI, 1.33-5.67) were at increased risk of adenocarcinoma. In contrast, breastfeeding was associated with reduced risk of nonadenocarcinoma (HR, 0.51; 95% CI, 0.28-0.92). No significant association with parity, age at first birth, exogenous hormone use, or length of menstrual cycle was detected.

Conclusions: Reproductive factors may play a role in lung carcinogenesis. Future studies that include estrogen and progesterone biomarkers may help clarify the role of endogenous hormones in lung carcinogenesis.

Impact: Fertility span and age at menopause may be useful variables in developing risk prediction models for lung adenocarcinoma among nonsmoking women.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1399DOI Listing
June 2021

Effectiveness of a Cancer Risk Prediction Tool on Lifestyle Habits: A Randomized Controlled Trial.

Cancer Epidemiol Biomarkers Prev 2021 Jun 26;30(6):1063-1071. Epub 2021 Mar 26.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, Japan.

Background: Risk prediction models offer a promising approach to lifestyle modification. We evaluated the effect of personalized advice based on cancer risk prediction in improving five lifestyle habits (smoking, alcohol consumption, salt intake, physical activity, and body mass index) compared with standard advice without risk prediction among a Japanese general population with at least one unhealthy lifestyle habit.

Methods: In a parallel-design, single-blind, randomized controlled trial between February 2018 and July 2019, 5984 participants aged 40-64 years with unhealthy lifestyle habits were recruited from persons covered under a life insurance policy. They were randomly assigned to an intervention or control group and received personalized or standard advice, respectively. They were also sent an invitation to participate in a lifestyle modification program aimed at improving lifestyle. Primary outcome was an improvement in lifestyle, defined as an increase in healthy lifestyle habits within 6 months.

Results: The proportion of participants who improved their lifestyle within 6 months in the intervention group did not significantly differ from that in the control group (18.4% vs. 17.7%; = 0.488). Among participants with low health literacy and two or fewer of five healthy habits, the proportion of participants subscribing to the lifestyle modification program was higher in the intervention group than in the control group.

Conclusions: Compared with standardized advice, personalized advice based on cancer risk prediction had no effect on improving lifestyle.

Impact: Provision of predicted cancer risk information did not induce change in unhealthy lifestyle.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1499DOI Listing
June 2021

Addition of hydrophobic side chains improve the apoptosis inducibility of the human glyoxalase I inhibitor, TLSC702.

Bioorg Med Chem Lett 2021 05 10;40:127918. Epub 2021 Mar 10.

Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address:

Glyoxalase I (GLO I) is a known therapeutic target in cancer. Even though TLSC702, a GLO I inhibitor that we discovered, induces apoptosis in tumor cells, exceptionally higher doses are required compared with those needed to inhibit GLO I activity in vitro. In this work, structure-activity optimization studies were conducted on four sections of the TLSC702 molecule to determine the partial structural features necessary for the inhibition of GLO I. Herein, we found that the carboxy group in TLSC702 was critical for binding with the divalent zinc at the active site of GLO I. In contrast, the side chain substituents in the meta- and para- positions of the benzene ring had little influence on the in vitro inhibition of GLO I. The CLogP values of the TLSC702 derivatives showed a positive correlation with the antiproliferative effects on NCI-H522 cells. Thus, two derivatives of TLSC702, which displayed either high or low lipophilicity due to the types of substituents at the phenyl position, were selected. Even though both derivatives showed comparable inhibitory effects as that of their parent compound, the derivative with the high CLogP value was distinctly more antiproliferative than TLSC702. In contrast, the derivative with the low CLogP value did not decrease cell viability in NCI-H522 and HL-60 cells. These findings suggested that structural improvements, such as the addition of hydrophobic moieties to the phenyl group, enhanced the ability of TLSC702 to induce apoptosis by increasing cell membrane permeability.
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http://dx.doi.org/10.1016/j.bmcl.2021.127918DOI Listing
May 2021

Risk of stroke in cancer survivors using a propensity score-matched cohort analysis.

Sci Rep 2021 Mar 10;11(1):5599. Epub 2021 Mar 10.

Epidemiology and Prevention Group, Center for Public Health Sciences, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Little is known about the risk of cerebrovascular disease in cancer survivors. We aimed to assess the association between incident cancer and the subsequent risk of stroke using a large-scale, population-based prospective study. 74,530 Japanese aged between 40 and 69 years at baseline study were matched by the status of cancer diagnosis during follow-up using propensity score nearest-neighbor matching with allowance for replacement. A total of 2242 strokes were reported during 557,885 person-years of follow-up. Associations between incident cancer and the subsequent risk of all strokes, cerebral infarction, and intracerebral hemorrhage were assessed using a Cox proportional hazards model stratified on the propensity score-matched pairs. No significant association was observed between the status of cancer diagnosis of all types, gastric, colorectal and lung cancer, and subsequent occurrence of all strokes, cerebral infarction, and intracerebral hemorrhage. However, analysis by discrete time periods suggested an elevated risk in cancer patients for one to three months after a cancer diagnosis in all stroke (HR, 2.24; 95% CI, 1.06, 4.74) and cerebral infarction (HR, 2.62; 95% CI, 1.05, 6.53). This prospective cohort study found no association between the status of cancer diagnosis and the subsequent occurrence of all strokes and its subtypes during the entire follow-up period but suggested an increase in stroke risk during the active phase of malignancy.
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http://dx.doi.org/10.1038/s41598-021-83368-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946896PMC
March 2021

Impact of reproductive factors on breast cancer incidence: Pooled analysis of nine cohort studies in Japan.

Cancer Med 2021 03 1;10(6):2153-2163. Epub 2021 Mar 1.

Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Prior studies reported the association of reproductive factors with breast cancer (BC), but the evidence is inconsistent. We conducted a pooled analysis of nine cohort studies in Japan to evaluate the impact of six reproductive factors (age at menarche/age at first birth/number of births/age at menopause/use of female hormones/breastfeeding) on BC incidence. We conducted analyses according to menopausal status at the baseline or at the diagnosis. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by applying Cox proportional-hazards model in each study. These hazard ratios were integrated using a random-effects model. Among 187,999 women (premenopausal: 61,113, postmenopausal: 126,886), we observed 873 premenopausal and 1,456 postmenopausal cases. Among premenopausal women, use of female hormones significantly increased BC incidence (HR: 1.53 [1.04-2.25]). Although P value for trend was not significant for age at first birth and number of births (P for trend: 0.15 and 0.30, respectively), women giving first birth at ages ≥36 experienced significantly higher BC incidence than at ages 21-25 years, and women who had ≥2 births experienced significantly lower BC incidence than nulliparous women. Among postmenopausal women, more births significantly decreased BC incidence (P for trend: 0.03). Although P value for trend was not significant for age at first birth and age at menopause (P for trend: 0.30 and 0.37, respectively), women giving first birth at ages 26-35 years experienced significantly higher BC incidence than at ages 21-25 years, and women with age at menopause: ≥50 years experienced significantly higher BC incidence than age at menopause: ≤44 years. BC incidence was similar according to age at menarche or breastfeeding history among both premenopausal and postmenopausal women. In conclusion, among Japanese women, use of female hormones increased BC incidence in premenopausal women, and more births decreased BC incidence in postmenopausal women.
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http://dx.doi.org/10.1002/cam4.3752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957169PMC
March 2021

Sugary Drink Consumption and Subsequent Colorectal Cancer Risk: The Japan Public Health Center-Based Prospective Cohort Study.

Cancer Epidemiol Biomarkers Prev 2021 Apr 9;30(4):782-788. Epub 2021 Feb 9.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: Most studies examining the associations of sugary drink consumption on colorectal cancer risk have been conducted in Western populations.

Methods: This study consisted of 74,070 participants in the Japan Public Health Center-based Prospective Study who completed a food frequency questionnaire (1995-1999). The participants were followed until December 2013 to investigate the associations between sugary drink consumption and colorectal cancer risk using Cox proportional hazards regression models.

Results: Among the 74,070 participants, mean age was 56.5 years at baseline, with a mean body mass index (BMI) of 23.5 and a mean daily consumption of 286 mL/day for men and 145 mL/day for women. During a follow-up of 15 years, 1,648 colorectal cancer cases were identified. No overall greater risk of colorectal cancer was observed among men [multivariable HR = 0.84; 95% confidence of interval (CI), 0.70-1.02; ≥254 mL/day vs. nonconsumers] and women (HR = 1.20; 95% CI, 0.96-1.50, ≥134 mL/day vs. nonconsumers). Sugary drink consumption was associated with colon cancer among women (HR = 1.36; 95% CI, 1.03-1.78, ≥134 mL/day vs. nonconsumers). HRs for proximal colon cancer among women who consumed sugary drinks, as compared with nonconsumers, were 1.47 (95% CI, 1.03-2.10) for sugary drink consumption less than 134 mL/day, and 1.45 (95% CI, 1.01-2.09) for at least 134 mL/day.

Conclusions: In this large prospective cohort of Japanese with a moderate sugary drink consumption level and low prevalence of obesity, we observed a 36% increased risk of colon cancer in women.

Impact: Our findings highlight the importance of subsite- and sex-specific investigation.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1364DOI Listing
April 2021

Alcohol consumption and breast cancer risk in Japan: A pooled analysis of eight population-based cohort studies.

Int J Cancer 2021 Jun 10;148(11):2736-2747. Epub 2021 Feb 10.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

Although alcohol consumption is reported to increase the incidence of breast cancer in European studies, evidence for an association between alcohol and breast cancer in Asian populations is insufficient. We conducted a pooled analysis of eight large-scale population-based prospective cohort studies in Japan to evaluate the association between alcohol (both frequency and amount) and breast cancer risk with categorization by menopausal status at baseline and at diagnosis. Estimated hazard ratios (HR) and 95% confidence intervals were calculated in the individual cohorts and combined using random-effects models. Among 158 164 subjects with 2 369 252 person-years of follow-up, 2208 breast cancer cases were newly diagnosed. Alcohol consumption had a significant association with a higher risk of breast cancer in both women who were premenopausal at baseline (regular drinker compared to nondrinker: HR 1.37, 1.04-1.81, ≥23 g/d compared to 0 g/d: HR 1.74, 1.25-2.43, P for trend per frequency category: P = .017) and those who were premenopausal at diagnosis (≥23 g/d compared to 0 g/d: HR 1.89, 1.04-3.43, P for trend per frequency category: P = .032). In contrast, no significant association was seen in women who were postmenopausal at baseline or at diagnosis, despite a substantial number of subjects and long follow-up period. Our results revealed that frequent and high alcohol consumption are both risk factors for Asian premenopausal breast cancer, similarly to previous studies in Western countries. The lack of a clear association in postmenopausal women in our study warrants larger investigation in Asia.
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http://dx.doi.org/10.1002/ijc.33478DOI Listing
June 2021

Working cancer survivors' physical and mental characteristics compared to cancer-free workers in Japan: a nationwide general population-based study.

J Cancer Surviv 2021 Jan 12. Epub 2021 Jan 12.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Purpose: This study compared working cancer survivors' self-rated health status (SRHS), physical functional capacity, depressive symptoms, and happiness to those of cancer-free workers.

Methods: A nationwide general population-based cross-sectional study on a sample of Japanese was conducted. Prevalence of deteriorated SRHS, restricted physical functional capacity, depressive symptoms, and perceived happiness were compared between working cancer survivors and cancer-free workers with multivariable logistic regression analysis adjusted for age and sociodemographic and health-related backgrounds.

Results: Of the 28,311 male and 26,068 female workers, 977 (3.5%) and 1267 (4.9%) were cancer survivors, respectively. Working cancer survivors reported deteriorated SRHS more frequently than cancer-free workers: 21.3% vs. 13.8%, multivariable-adjusted odds ratio (95% confidence interval), 1.64 (1.39-1.95) for men, 23.8% vs. 17.5%, 1.34 (1.16-1.54) for women. Restricted physical functional capacity was reported more frequently in working cancer survivors than cancer-free workers: 6.8% vs. 2.6%, 1.76 (1.34-2.32) for men, 4.9% vs. 2.0%, 2.06 (1.56-2.71) for women. No significant difference was found for depressive symptoms: 21.6% vs. 22.9% in men, 30.0% vs. 28.5% in women. Working cancer survivors felt happiness more frequently than cancer-free survivors in men (77.3% vs. 71.7%, 1.21 (1.01-1.45)) but not in women (76.1% vs. 74.9%).

Conclusions: Working cancer survivors had worse SRHS and more restricted physical functional capacity than cancer-free workers. In men, working cancer survivors felt happiness more frequently than cancer-free workers.

Implications For Cancer Survivors: Continuous support to improve cancer survivors' SRHS and physical functional capacity would be necessary even while they are working.
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http://dx.doi.org/10.1007/s11764-020-00984-7DOI Listing
January 2021

Dietary fiber intake and risk of gastric cancer: The Japan Public Health Center-based prospective study.

Int J Cancer 2021 Jun 30;148(11):2664-2673. Epub 2020 Dec 30.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Centre, Tokyo, Japan.

Evidence of the association between dietary fiber intake and gastric cancer (GC) risk from prospective studies is limited. We examined the association between dietary fiber intake and GC risk in a large prospective study. A total of 91 946 eligible Japanese aged 45 to 74 years (42 773 men and 49 173 women) participated in a population-based cohort study (Japan Public Health Center-based prospective study). From a validated food frequency questionnaire with 138 food items, total and food source-specific dietary fiber intake was calculated as exposure. The hazard ratio (HR) and the 95% confidence interval (CI) of GC incidence according to quintile of dietary fiber intake were examined after adjusting for confounding factors. In total, 2228 GC cases (1559 men and 669 women) were observed during the 15.0 years follow-up. Total dietary fiber intake was not associated with GC risk; however, a marginally increased risk trend because of high HR in the highest quintile of total fiber intake was found in women (HR [95% CI] in Q5 vs Q1: 0.95 [0.79-1.14], P for trend .30 in men, HR [95% CI] 1.25 [0.98-1.61], P for trend .05 in women). Stratification by tumor location did not change the results. A marginal but not significant inverse trend was observed regarding cereal fiber intake and GC risk in men. Total dietary fiber intake was not associated with GC risk. Further studies are warranted to confirm this association.
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http://dx.doi.org/10.1002/ijc.33450DOI Listing
June 2021

Fermented and nonfermented soy foods and the risk of breast cancer in a Japanese population-based cohort study.

Cancer Med 2021 01 19;10(2):757-771. Epub 2020 Dec 19.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Japan.

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.
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http://dx.doi.org/10.1002/cam4.3677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877355PMC
January 2021

Associations of coffee and tea consumption with lung cancer risk.

Int J Cancer 2020 Dec 16. Epub 2020 Dec 16.

Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, South Korea.

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment.
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http://dx.doi.org/10.1002/ijc.33445DOI Listing
December 2020

Association between meat intake and mortality due to all-cause and major causes of death in a Japanese population.

PLoS One 2020 15;15(12):e0244007. Epub 2020 Dec 15.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, Japan.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244007PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737902PMC
February 2021

Novel predictive factors for patient discomfort and severe cough during bronchoscopy: A prospective questionnaire analysis.

PLoS One 2020 19;15(10):e0240485. Epub 2020 Oct 19.

Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.

During bronchoscopy, discomfort is mainly caused by an unavoidable cough; however, there are no reports of any predictive factors for strong cough during bronchoscopy identified before the procedure. To clarify the factors underlying the discomfort status and predictive factors for strong cough during bronchoscopy, we prospectively evaluated patients who underwent bronchoscopy at Kyorin University Hospital between March 2018 and July 2019. Before and after bronchoscopy, the enrolled patients answered a questionnaire regarding the procedure. At the same time, bronchoscopists evaluated cough severity using a four-grade cough scale. We evaluated patient characteristics and predictive factors associated with bronchoscopy from the perspective of discomfort and strong cough. A total of 172 patients were ultimately enrolled in this study. On multivariate logistic regression analysis, comparison of the subjective data between the discomfort and comfort groups revealed that factors that were more common in the former group were younger age (OR = 0.96, p = 0.002), less experienced bronchoscopist (OR = 2.08, p = 0.047), and elevation of cough score per 1 point (OR = 1.69, p < 0.001). Furthermore, the predictive factors for strong cough prior to performing bronchoscopy were female sex (OR = 2.57, p = 0.009), EBUS-TBNA (OR = 2.95, p = 0.004), and prolonged examination time of more than 36 min (OR = 2.32, p = 0.022). Regarding patients' discomfort, younger age, less experienced bronchoscopist, and the elevation of cough score per 1 point were important factors for discomfort in bronchoscopy. On the other hand, female sex, EBUS-TBNA, and prolonged examination time were crucial factors for strong cough.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240485PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571709PMC
December 2020

Low carbohydrate diet and all cause and cause-specific mortality.

Clin Nutr 2021 Apr 23;40(4):2016-2024. Epub 2020 Sep 23.

Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: Evidence is limited regarding the association between low-carbohydrate diet (LCD) score and mortality among Asians, a population that consumes a large amount of carbohydrates.

Objective: The present study examined the association between low-carbohydrate diet (LCD) score (based on percentage of energy as carbohydrate, fat, and protein) and the risk of total and cause-specific mortality among Asians.

Design: This study was a prospective cohort study in Japan with follow-up for a median of 16.9 years involving 43008 men and 50646 women aged 45-75 years. Association of LCD score, LCD score based on animal sources of protein and fat, and LCD score based on plant sources of protein and fat with risk of mortality was assessed using Cox proportional hazards model.

Results: A U-shaped association was observed between LCD score and total mortality: the multivariable-adjusted hazard ratios (HRs) (95% CI) of total mortality for lowest through highest scores were 1.00, 0.95 (0.91, 1.01), 0.93 (0.88, 0.98), 0.93 (0.88, 0.98), and 1.01 (0.95, 1.07) (P-non-linearity <0.01). A similar association was found for mortality from cardiovascular disease (CVD) and heart disease. LCD score based on carbohydrate, animal protein, and animal fat also showed a U-shaped association for total mortality (P-non-linearity <0.01). In contrast, LCD score based on carbohydrate, plant protein, and plant fat was linearly associated with lower total (HR, 0.89; 95% CI: 0.83, 0.94 for highest versus lowest quintile), CVD [0.82 (0.73, 0.92)], heart disease [0.83 (0.71, 0.98)], and cerebrovascular disease [0.75 (0.62, 0.91) mortality.

Conclusions: Both LCD with high animal protein and fat and high-carbohydrate diet with low animal protein and fat were associated with higher risk of mortality. Meanwhile, LCD high in plant-based sources of protein and fat was associated with a lower risk of total and CVD mortality.
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http://dx.doi.org/10.1016/j.clnu.2020.09.022DOI Listing
April 2021

Soy and isoflavone consumption and subsequent risk of prostate cancer mortality: the Japan Public Health Center-based Prospective Study.

Int J Epidemiol 2020 10;49(5):1553-1561

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: Although many epidemiological studies have reported the preventive effects of soy products and isoflavones on prostate cancer, our previous studies reported that the association between soy and isoflavones and prostate cancer incidence differed according to stage. It is more important to identify modifiable risk factors related to lethal prostate cancer. Here, we investigated the association between soy, soy products and isoflavones intake and prostate cancer mortality, in a prospective study in Japan.

Methods: We conducted a population-based prospective study in 43 580 Japanese men with no history of cancer or cardiovascular disease (aged 45-74 years). Participants completed a validated questionnaire which included 138 food items. We followed participants from 1995 to 2016. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer mortality were calculated according to quintiles of soy products and isoflavones intake, using Cox hazard proportional hazards regression.

Results: During 16.9 years follow-up, we registered 221 deaths from prostate cancer. Isoflavones and soy products intake was associated with an increased risk of prostate cancer death, with multivariate HRQ5 vs. Q1=1.39, 95% CI = 0.87-2.20, p for trend = 0.04 for isoflavones and multivariate HRQ5 vs. Q1=1.76, 95% CI = 1.10-2.82, p for trend = 0.04 for soy food.

Conclusions: Our study suggested that high intake of soy and isoflavones might increase the risk of prostate cancer mortality.
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http://dx.doi.org/10.1093/ije/dyaa177DOI Listing
October 2020

Fermented soy products intake and risk of cardiovascular disease and total cancer incidence: The Japan Public Health Center-based Prospective study.

Eur J Clin Nutr 2021 06 4;75(6):954-968. Epub 2020 Sep 4.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background/objectives: The association of fermented soy products, separately from total soy products, with cardiovascular disease (CVD) and total cancer has not been reported. We examined this association in a population-based prospective cohort study in Japan.

Subjects/methods: We studied 79,648 participants (42,788 women; 36,860 men) aged 45-74 years without a history of cancer, myocardial infarction, or stroke. Participants completed a food frequency questionnaire (1995-1998) and were followed to 2009-2012. Cox proportional hazards regression analysis was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of incidence of CVD and total cancer according to quartiles of total soy products, nonfermented soy products, fermented soy products, miso soup, natto, total isoflavones from soy products, isoflavones from nonfermented soy products, and isoflavones from fermented soy products.

Results: In women, we observed a significant inverse association between fermented soy product intake and the risk of CVD (multivariate HR in the highest compared with the lowest quartile of fermented soy product intake: 0.80; 95% CI: 0.68, 0.95; P for trend = 0.010), and also found significant inverse associations for natto and isoflavones among fermented soy products. In site-specific analysis, we observed a similar, significant inverse association between fermented soy product intake and the risk of stroke in women. We found no significant association between any soy product and risk of CVD in men or total cancer in both sexes.

Conclusions: Intake of fermented soy products such as natto was inversely associated with the risk of CVD in women.
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http://dx.doi.org/10.1038/s41430-020-00732-1DOI Listing
June 2021