Development and Validation of a Cardiovascular Disease Risk Prediction Model for the Japanese Working Population: The Japan Epidemiology Collaboration on Occupational Health Study.

AIMS: This study aimed to develop a cardiovascular disease (CVD) risk model using data from a large occupational cohort. METHODS: A risk prediction model was developed using the routine health checkup data of 96,117 Japanese employees (84.0% men) who were 30-64 years of age and had no CVD at baseline. Cox proportional hazards regression models were employed to develop a risk model for assessing the 10-year CVD risk. Measures of discrimination and calibration were used to assess the predictive performance of the model and internal validation was used to examine potential overfitting. RESULTS: During a mean follow-up period of 6.7 years (range, 0.1-11.0 years), 422 cases of incident CVD were confirmed. The final model, which included predictor variables of age, smoking, diabetes, systolic blood pressure, and low- and high-density lipoprotein cholesterol levels, demonstrated a good predictive ability (Harrell's C-statistic, 0.796; 95% confidence interval, 0.775-0.817) with excellent calibration between observed and predicted values. Internal validation revealed minimal overfitting. CONCLUSIONS: The developed model can accurately predict the 10-year CVD risk. Because it is based on routine health checkup data, the prediction model can be easily implemented in the workplace. Further studies are required to assess the external validity and transferability of the proposed CVD risk model.

Association of conventional cigarette smoking, heated tobacco product use and dual use with hypertension.

BACKGROUND: Heated tobacco products (HTPs) have emerged as alternatives to conventional cigarettes. However, their health effects remain largely unknown. This study aimed to prospectively explore the association between the use of cigarettes and HTPs and the risk of hypertension. METHODS: This cohort study analysed data from 30 152 workers (82.0% men, mean age 42.9 ± 11.0 years) who were initially free of hypertension, participating in the Japan Epidemiology Collaboration on Occupational Health Study. Participants were categorized into five groups based on their self-reported tobacco product use: never smokers, past smokers, exclusive cigarette smokers, exclusive HTP users and dual users of cigarettes and HTPs. Hypertension cases were identified using three data points from annual health checkup data collected between 2019 and 2021. Cox proportional hazards regression models were used to investigate the association between tobacco product use and hypertension. RESULTS: During a mean follow-up of 2.6 years (range: 0.1-4.0 years), 3656 new cases of hypertension were identified. Compared with never smokers, the risk of hypertension was higher among exclusive cigarette smokers [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.13-1.41] and exclusive HTP users (HR 1.19, 95% CI 1.06-1.34). There was also a suggestion of increased risk of hypertension among dual users (HR 1.16, 95% CI 0.98-1.38). Furthermore, the risk of hypertension increased with the intensity of cigarette/HTP use in all tobacco product users. CONCLUSIONS: Similarly, both cigarette smoking and HTP use elevate the risk of hypertension. HTPs should not be regarded as less harmful alternatives to traditional cigarettes for preventing hypertension.

Association of conventional cigarette smoking, heated tobacco product use, and dual use with hearing loss: A working population-based study.

INTRODUCTION: Although conventional cigarette smoking has been linked to an increased risk of hearing loss, the association between heated tobacco products (HTPs) and hearing loss is unknown. The objective of this study was to investigate the association between cigarette and HTP use and hearing loss. METHODS: This cross-sectional study examined the data of 7769 employees from five companies (Study I) and 34404 employees from a large company (Study II), all participants in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into five groups based on their self-reported tobacco use: never smokers, former smokers, exclusive cigarette smokers, exclusive users of HTPs, and those who used both cigarettes and HTPs. Hearing levels were measured using pure-tone audiometry at 1 and 4 kHz frequencies. Separate analyses were carried out for each study, and the results were then combined using fixed-effect models to pool the estimates. RESULTS: The analysis included 42173 participants, with a prevalence of 12.9% for exclusive cigarette smoking, 9.8% for exclusive HTP use, and 5.5% for dual use. The pooled adjusted odds ratios with 95% confidence intervals for unilateral hearing loss at 4 kHz were 1.21 (95% CI: 1.10-1.33) for former smokers, 1.83 (95% CI: 1.64-2.05) for exclusive cigarette smokers,1.46 (95% CI: 1.28-1.67) for exclusive HTP users, and 1.66 (95% CI: 1.41-1.96) for dual users, compared to never smokers. Additionally, the adjusted odds ratios for hearing loss at 4 kHz among exclusive cigarette smokers, exclusive HTP users, and dual users increased with the intensity of cigarette/HTP consumption (all p for trend <0.001). No significant associations were found between exclusive HTP use, dual use, and hearing loss at 1 kHz, apart from exclusive cigarette smoking. CONCLUSIONS: In this cross-sectional study, associations were found between exclusive cigarette smoking, exclusive HTP use, dual use, and hearing loss, particularly at 4 kHz. Further research is needed to confirm these findings.

Vitamin D deficiency during the coronavirus disease 2019 (COVID-19) pandemic among healthcare workers.

BACKGROUND & AIMS: Vitamin D deficiency is a common nutritional problem worldwide that may have worsened during the coronavirus disease 2019 (COVID-19) pandemic. The present study sought to examine the prevalence and correlates of vitamin D deficiency among healthcare workers three years after the start of the COVID-19 pandemic. METHODS: Participants comprised 2543 staff members from a medical research institute, who completed a questionnaire and donated blood samples in June 2023. 25-hydroxyvitamin D (25[OH]D) levels were measured using an electrochemiluminescence immunoassay. Logistic regression was used to calculate the odds ratio and its 95% confidence interval while adjusting for covariates. RESULTS: The proportions of participants with vitamin D insufficiency (25[OH]D 20-29 ng/mL) and deficiency (25[OH]D < 20 ng/mL) were 44.9% and 45.9%, respectively. In a multivariable-adjusted model, factors associated with a higher prevalence of vitamin D deficiency included younger age, female sex, fewer hours of daytime outdoor physical activity during leisure time (without regular use of sunscreen), lower intake of fatty fish, no use of vitamin D supplements, smoking, and no alcohol consumption. Occupational factors, including shift work, were not independently associated with vitamin D deficiency. CONCLUSIONS: Our results suggest that vitamin D insufficiency and deficiency are highly prevalent among healthcare workers. Health education regarding lifestyle modifications for this occupational group are warranted to improve their vitamin D status in the COVID-19 era.

Body mass index and lung cancer risk: Pooled analysis of 10 prospective cohort studies in Japan.

Mounting evidence suggests that body mass index (BMI) is inversely associated with the risk of lung cancer. However, relatively few studies have explored this association in Asian people, who have a much lower prevalence of obesity than Caucasians. We pooled data from 10 prospective cohort studies involving 444,143 Japanese men and women to address the association between BMI and the risk of lung cancer. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in each cohort using the Cox proportional hazards model. A meta-analysis was undertaken by combining the results from each cohort. Heterogeneity across studies was evaluated using Cochran's Q and I2statistics. During 5,730,013 person-years of follow-up, 6454 incident lung cancer cases (4727 men and 1727 women) were identified. Baseline BMI was inversely associated with lung cancer risk in men and women combined. While leanness (BMI <18.5) was associated with a higher risk of lung cancer (HR 1.35; 95% CI, 1.16-1.57), overweight and obesity were associated with a lower risk, with HRs of 0.77 (95% CI, 0.71-0.84) and 0.69 (95% CI, 0.45-1.07), respectively. Every 5 kg/m2 increase in BMI was associated with a 21% lower risk of lung cancer (HR 0.79; 95% CI, 0.75-0.83; p < 0.0001). Our pooled analysis indicated that BMI is inversely associated with the risk of lung cancer in the Japanese population. This inverse association could be partly attributed to residual confounding by smoking, as it was more pronounced among male smokers.

Should insulin resistance (HOMA-IR), insulin secretion (HOMA-ß), and visceral fat area be considered for improving the performance of diabetes risk prediction models.

INTRODUCTION: Insulin resistance and defects in pancreatic beta cells are the two major pathophysiologic abnormalities that underlie type 2 diabetes. In addition, visceral fat area (VFA) is reported to be a stronger predictor for diabetes than body mass index (BMI). Here, we tested whether the performance of diabetes prediction models could be improved by adding HOMA-IR and HOMA-ß and replacing BMI with VFA. RESEARCH DESIGN AND METHODS: We developed five prediction models using data from a cohort study (5578 individuals, of whom 94.7% were male, and 943 had incident diabetes). We conducted a baseline model (model 1) including age, sex, BMI, smoking, dyslipidemia, hypertension, and HbA1c. Subsequently, we developed another four models: model 2, predictors in model 1 plus fasting plasma glucose (FPG); model 3, predictors in model 1 plus HOMA-IR and HOMA-ß; model 4, predictors in model 1 plus FPG, HOMA-IR, and HOMA-ß; model 5, replaced BMI with VFA in model 2. We assessed model discrimination and calibration for the first 10 years of follow-up. RESULTS: The addition of FPG to model 1 obviously increased the value of the area under the receiver operating characteristic curve from 0.79 (95% CI 0.78, 0.81) to 0.84 (0.83, 0.85). Compared with model 1, model 2 also significantly improved the risk reclassification and discrimination, with a continuous net reclassification improvement index of 0.61 (0.56, 0.70) and an integrated discrimination improvement index of 0.09 (0.08, 0.10). Adding HOMA-IR and HOMA-ß (models 3 and 4) or replacing BMI with VFA (model 5) did not further materially improve the performance. CONCLUSIONS: This cohort study, primarily composed of male workers, suggests that a model with BMI, FPG, and HbA1c effectively identifies those at high diabetes risk. However, adding HOMA-IR, HOMA-ß, or replacing BMI with VFA does not significantly improve the model. Further studies are needed to confirm our findings.

Adult Height and Risk of Colorectal Cancer: A Pooled Analysis of 10 Population-based Cohort Studies in Japan.

BACKGROUND: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. METHODS: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. RESULTS: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07-1.40), 1.22 (95% CI, 1.09-1.36), and 1.27 (95% CI, 1.08-1.49), respectively, in men and 1.21 (95% CI, 1.09-1.35), 1.23 (95% CI, 1.08-1.40), and 1.35 (95% CI, 1.003-1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. CONCLUSION: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Diabetes, Prediabetes, and the Risk of a Composite Outcome of Long-term Sickness Absence and Pre-retirement Death Due to Physical Disorders.

BACKGROUND: Diabetes and prediabetes have been linked with morbidity or mortality from cardiovascular disease, cancer, or other physical disorders among working-age populations, but less is known about outcomes directly related to labor loss (eg, Tlong-term sickness absence [LTSA] or pre-retirement death due to physical disorders).This prospective study aimed to examine the association of diabetes and prediabetes with the risk of a composite outcome of LTSA and pre-retirement death due to physical disorders. The present study also examined the associations of severe outcomes (LTSA or death) due to specific physical disorders or injuries/external causes in relation to diabetes and prediabetes. METHODS: Data were derived from the Japan Epidemiology Collaboration on Occupational Health study. A total of 60,519 workers from 12 companies were followed for 8 years. Diabetes and prediabetes were defined based on the American Diabetes Association criteria. A Cox proportional hazards regression model was used to examine the association between diabetes/prediabetes and severe outcomes due to physical disorders or injuries/external causes. RESULTS: The adjusted hazard ratios of severe outcomes due to all physical disorders were 1.22 (95% confidence interval [CI], 1.02-1.45) and 2.32 (95% CI, 2.04-2.64) for prediabetes and diabetes, respectively. In cause-specific analyses, an increased risk was observed for severe outcomes due to cancers, cardiovascular diseases, diseases of the musculoskeletal system, and injuries/external causes in relation to either or both diabetes and prediabetes. CONCLUSION: Diabetes and prediabetes were associated with an increased risk of severe outcomes due to physical disorders or injuries/external causes among Japanese workers.

Metabolic syndrome and the risk of severe cancer events: a longitudinal study in Japanese workers.

BACKGROUND: Metabolic syndrome (MetS) is associated with cancer risk; however, little is known regarding its relationship with the risk of cancer-related premature death and long-term sick leave (LTSL), which can lead to a substantial loss in working years. The present study aimed to quantify the all-site and site-specific associations between MetS and the risk of severe cancer events (a composite outcome of LTSL and mortality due to cancer) in a large working population in Japan. METHODS: We recruited 70,875 workers (59,950 men and 10,925 women), aged 20-59 years, who attended health check-ups in 2011 (10 companies) and 2014 (2 companies). All workers underwent follow up for severe cancer events until March 31, 2020. MetS was defined in accordance with the Joint Interim Statement. Cox regression models were used to quantify the association between baseline MetS and severe cancer events. RESULTS: During 427,379 person-years of follow-up, 523 participants experienced the outcome consisting of 493 LTSLs of which 124 eventually resulted in death, and 30 deaths without taking LTSL. The adjusted hazard ratios (HR) (95% confidence intervals [CI]) for composite severe events due to all-site, obesity-related, and non-obesity-related cancer among those with vs. without MetS were 1.26 (1.03, 1.55), 1.37 (1.04, 1.82), and 1.15 (0.84, 1.56), respectively. In cancer site-specific analyses, MetS was associated with an increased risk of severe events due to pancreatic cancer (HR, 2.06; 95% CI, 0.99-4.26). When mortality was treated solely as the endpoint, the association was significant for all-site (HR, 1.58; 95% CI, 1.10-2.26), and obesity-related (HR, 1.59; 95% CI, 1.00-2.54) cancer. Additionally, a greater number of MetS components was associated with a greater risk of both severe cancer events and cancer-related mortality (P trend < 0.05). CONCLUSION: Among Japanese workers, MetS was associated with an increased risk of severe cancer events, especially those due to obesity-linked cancer.

Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine.

OBJECTIVES: To examine the differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination. METHODS: Throughout the pandemic, we evaluated the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients over time among the staff of a medical and research center in Tokyo. Linear mixed models were used to estimate trajectories of antibody titers from 14 to 180 days after the last immune-conferred event (vaccination or infection) and compare antibody waning rates across prior infection and vaccination status, and across background factors in infection-naïve participants. RESULTS: A total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (percentage per 30 days [95% CI]) was slower after 3 doses (25% [23-26]) than 2 doses (36% [35-37]). Participants with hybrid immunity (vaccination and infection) had further slower waning rates: 2-dose plus infection (16% [9-22]); 3-dose plus infection (21% [17-25]). Older age, male sex, obesity, coexisting diseases, immunosuppressant use, smoking, and alcohol drinking were associated with lower antibody titers, whereas these associations disappeared after 3 doses, except for sex (lower in female participants) and immunosuppressant use. Antibody waned slightly faster in older participants, females, and alcohol drinkers after 2 doses, whereas it did not differ after 3 doses across except sex. DISCUSSION: The 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection modestly enhanced its durability. The antibody levels at a given time point and waning speed after 2 doses differed across background factors; however, these differences mostly diminished after 3 doses.

Body mass index and esophageal and gastric cancer: A pooled analysis of 10 population-based cohort studies in Japan.

The effect of body mass index (BMI) on esophageal and gastric carcinogenesis might be heterogeneous, depending on subtype or subsite. However, findings from prospective evaluations of BMI associated with these cancers among Asian populations have been inconsistent and limited, especially for esophageal adenocarcinoma and gastric cardia cancer. We performed a pooled analysis of 10 population-based cohort studies to examine this association in 394,247 Japanese individuals. We used Cox proportional hazards regression to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs), then pooled these estimates to calculate summary HRs with a random effects model. During 5,750,107 person-years of follow-up, 1569 esophageal cancer (1038 squamous cell carcinoma and 86 adenocarcinoma) and 11,095 gastric (728 cardia and 5620 noncardia) cancer incident cases were identified. An inverse association was observed between BMI and esophageal squamous cell carcinoma (HR per 5-kg/m2 increase 0.57, 95% CI 0.50-0.65), whereas a positive association was seen in gastric cardia cancer (HR 1.15, 95% CI 1.00-1.32). A nonsignificant and significant positive association for overweight or obese (BMI ≥25 kg/m2 ) relative to BMI <25 kg/m2 was observed with esophageal adenocarcinoma (HR 1.32, 95% CI 0.80-2.17) and gastric cardia cancer (HR 1.24, 95% CI 1.05-1.46), respectively. No clear association with BMI was found for gastric noncardia cancer. This prospective study-the largest in an Asian country-provides a comprehensive quantitative estimate of the association of BMI with upper gastrointestinal cancer and confirms the subtype- or subsite-specific carcinogenic impact of BMI in a Japanese population.

Underlying medical conditions and anti-SARS-CoV-2 spike IgG antibody titers after two doses of BNT162b2 vaccination: A cross-sectional study.

Patients with underlying medical conditions are at high risk of developing serious symptoms of the coronavirus disease 2019 than healthy individuals; therefore, it is necessary to evaluate the immune response to vaccination among them to formulate precision and personalized vaccination strategies. However, inconsistent evidence exists regarding whether patients with underlying medical conditions have lower anti-SARS-CoV-2 spike IgG antibody titers. We performed a cross-sectional study enrolling 2762 healthcare workers who received second doses of BNT162b2 vaccination from three medical and research institutes between June and July, 2021. Medical conditions were surveyed by a questionnaire, and spike IgG antibody titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 62 days after the second vaccination. Multilevel linear regression model was used to estimate geometric mean and ratio of mean (95% confidence interval, CI) for the presence and absence of medical conditions and treatments. Among all participants (median age, 40 years [interquartile range, 30-50]; male proportion, 29.4%), the prevalence of hypertension, diabetes, chronic lung disease, cardiovascular disease, and cancer was 7.5%, 2.3%, 3.8%, 1.8%, and 1.3%, respectively. Patients with treated hypertension had lower antibody titers than those without hypertension; the multivariable-adjusted ratio of mean (95% CI) was 0.86 (0.76-0.98). Patients with untreated and treated diabetes had lower antibody titers than those without diabetes; the multivariable-adjusted ratio of mean (95% CI) was 0.63 (0.42-0.95) and 0.77 (0.63-0.95), respectively. No substantial difference was observed between the presence or absence of chronic lung disease, cardiovascular disease, or cancer. Patients with untreated hypertension and patients with untreated and treated diabetes had lower spike IgG antibody titers than participants without those medical conditions, suggesting that continuous monitoring of antibody titers and further booster shots could be necessary to maintain adaptive immunity in patients with hypertension or diabetes.

Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies.

In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review and meta-analysis of published studies evaluating patient response to antiviral therapy for chronic hepatitis C on the risk of HCC occurrence in Japan. Articles were searched using terms determined a priori through PubMed, screened by title and abstract, and selected by full-text assessment according to criteria determined a priori, including HCC occurrence in response to interferon (IFN)-based or IFN-free therapy, Japanese study, and 2 or more years of follow-up. We excluded studies on HCC recurrence. We calculated the pooled estimate of the crude incidence rate ratio with data from the selected studies using the person-years method with Poisson regression model and pooled estimate of the hazard ratio adjusted for potential confounders reported by the studies using a random effects model. A total of 26 studies were identified, all of which examined only IFN-based therapy as a result of the selection process. The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.33-0.43) for sustained virologic response (SVR) and 1.70 (1.61-1.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.19-0.26) for the incidence rate ratio (SVR vs. non-SVR). The pooled estimate of the hazard ratio (95% CI) of HCC incidence adjusted for potential confounders of 8 studies was 0.25 (0.19-0.34). SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence.

Prevalence of family history of cancer in the NC-CCAPH consortium of Japan.

The objective of this study was to identify the prevalence of family history of cancer using cohorts participating in the Japanese National Center Cohort Collaborative for Advancing Population Health (NC-CCAPH). We pooled data from seven eligible cohorts of the Collaborative with available data on family history of cancer. Prevalence of family history of cancer and corresponding 95% confidence intervals are presented for all cancers and selected site-specific cancers for the total population and stratified by sex, age, and birth cohort. Prevalence of family history of cancer increased with age ranging from 10.51% in the 15 to 39 year age category to 47.11% in 70-year-olds. Overall prevalence increased in birth cohorts from ≤ 1929 until 1960 and decreased for the next two decades. Gastric cancer (11.97%) was the most common site recorded for family members, followed by colorectal and lung (5.75%), prostate (4.37%), breast (3.43%) and liver (3.05%) cancer. Women consistently had a higher prevalence of family history of cancer (34.32%) versus men (28.75%). Almost one in three participants had a family history of cancer in this Japanese consortium study highlighting the importance of early and targeted cancer screening services.

Metabolic Syndrome and the Increased Risk of Medically Certified Long-term Sickness Absence: A Prospective Analysis Among Japanese Workers.

BACKGROUND: Metabolic syndrome (MetS) has been associated with various chronic diseases that may lead to long-term sickness absence (LTSA), but there is lacking information on the direct association between MetS and LTSA. The present study aimed to investigate the all-cause and cause-specific associations between MetS and the risk of medically certified LTSA among Japanese workers. METHODS: We recruited 67,403 workers (57,276 men and 10,127 women), aged 20-59 years from 13 companies in Japan during their health check-ups in 2011 (11 companies) and 2014 (2 companies), and we followed them for LTSA events (≥30 consecutive days) until March 31, 2020. MetS was defined according to the Joint Interim Statement. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for LTSA associated with MetS and its components. RESULTS: During 408,324 person-years of follow-up, 2,915 workers experienced LTSA. The adjusted HR for all-cause LTSA was 1.54 (95% CI, 1.41-1.68) among those with MetS compared to those without MetS. In cause-specific analysis, HRs associated with MetS significantly increased for LTSA due to overall physical disorders (1.76); cardiovascular diseases (3.16); diseases of the musculoskeletal system and connective tissue (2.01); cancers (1.24); obesity-related cancers (1.35); mental, behavioral, and neurodevelopmental disorders (1.28); reaction to severe stress and adjustment disorders (1.46); and external causes (1.46). The number of MetS components were also significantly associated with increased LTSA risk. CONCLUSION: MetS was associated with an increase in the risk of LTSA due to various diseases among Japanese workers.

Cigarette Smoking, Smoking Cessation, and Bladder Cancer Risk: A Pooled Analysis of 10 Cohort Studies in Japan.

BACKGROUND: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan. METHODS: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan. The risk associated with smoking behaviors was estimated using Cox regression models within each study, and pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for the incidence of bladder cancer were calculated. RESULTS: During 4,729,073 person-years of follow-up, 936 men and 325 women developed bladder cancer. In men, former smokers (HR 1.47; 95% CI, 1.18-1.82) and current smokers (HR 1.96; 95% CI, 1.62-2.38) had higher risk than never smokers. In women, current smokers had higher risk than never smokers (HR 2.35; 95% CI, 1.67-3.32). HRs in men linearly increased with increasing pack-years. Risk decreased with increasing years of smoking cessation in men, with a significant dose-response trend. Former smokers with a duration of more than 10 years after smoking cessation had no significantly increased risk compared with never smokers (HR 1.26; 95% CI, 0.97-1.63). CONCLUSION: Data from a pooled analysis of 10 population-based cohort studies in Japan clearly show an association between cigarette smoking and bladder cancer risk. The risk of smokers may approximate that of never smokers following cessation for many years.

Heated tobacco product use and abnormal glucose metabolism: a working population-based study.

AIMS: We aimed to assess the cross-sectional association of heated tobacco product (HTP) use with prediabetes and diabetes. METHODS: The present analysis included 8950 workers from 5 companies (Study I) and 31,341 workers from another large company (Study II), who participated in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were divided into five groups: never smokers, past smokers, exclusive HTP users, dual users of cigarettes and HTPs, and exclusive cigarette smokers. Diabetes and prediabetes were defined according to the fasting blood glucose and HbA1c levels and self-reported diabetes treatment, using the American Diabetes Association criteria. We analyzed the data of Study I and II separately, and then pooled these estimates using the fixed-effect models, with adjustment for a wide range of covariates. RESULTS: In this study that included 40,291 participants (mean age, 46.6 years; men, 84.3%), about half of the current tobacco-related product users reported using HTPs. Exclusive HTP users had higher odds of prediabetes (pooled odds ratio 1.36; 95% CI 1.25-1.47) and diabetes (1.68; 95% CI 1.45-1.94) than never smokers. Similarly, dual users also had increased odds of prediabetes (pooled odds ratio, 1.26; 95% CI 1.13-1.39) and diabetes (1.93; 95% CI 1.63-2.29). The strength of these associations was comparable to that of cigarette smokers. We observed significantly higher HbA1c and fasting blood glucose levels among both exclusive HTP users and dual users compared to never smokers. CONCLUSION: HTP use was associated with an increased likelihood of prediabetes and diabetes. Prospective studies are warranted to confirm the cross-sectional association.

Heated tobacco products and circulating high-density lipoprotein cholesterol concentrations.

We aimed to assess the association between heated tobacco product (HTP) use and high-density lipoprotein cholesterol (HDL-C) concentration. Our study included 12,268 workers from five companies (Study I) and 36,503 workers from another large company (Study II). Participants were categorized into five groups: never smokers, past smokers, exclusive HTP users, dual users of cigarettes and HTPs, and exclusive cigarette smokers. We analyzed the data of Studies I and II separately and then pooled these estimates using a fixed-effect model. Of the 48,771 participants, 9.3% were exclusive HTP users, and 6.0% were dual users. Exclusive HTP users had modestly but significantly lower concentrations of HDL-C than never smokers, with the pooled mean difference being - 1.1 (95% CI - 1.5 to - 0.6) mg/dL. Dual users showed a further reduction (mean difference - 3.7 (- 4.2 to - 3.2) mg/dL), which was comparable to that of exclusive cigarette smokers versus never smokers (mean difference - 4.3 (- 4.7 to - 3.9) mg/dL). The pooled odds ratios (95% CIs) of having low HDL-C (< 40 mg/dL for men and 50 mg/dL for women) were 1, 0.99 (0.90-1.11), 1.25 (1.09-1.43), 2.02 (1.76-2.32), and 2.09 (1.88-2.32) for never smokers, past smokers, exclusive HTP users, dual users, and exclusive cigarette smokers, respectively. In conclusion, exclusive HTP users had lower HDL-C concentrations than never smokers, although higher than exclusive cigarette smokers. Moreover, dual users had HDL-C concentrations similar to those in exclusive cigarette smokers.

Use of heated tobacco products, moderate alcohol drinking, and anti-SARS-CoV-2 IgG antibody titers after BNT162b2 vaccination among Japanese healthcare workers.

The effect of heated tobacco products (HTPs) use and moderate alcohol drinking on immunogenicity to coronavirus disease (COVID-19) vaccines remain elusive. This study aimed to examine the association of tobacco product use and alcohol consumption with anti-SARS-CoV-2 spike IgG antibody titers after the BNT162b2 vaccine. Participants were 3433 healthcare workers receiving two vaccine doses in the 4 national centers for advanced medical and research in Japan. Smoking status and alcohol consumption were assessed via a questionnaire, and anti-SARS-CoV-2 spike IgG titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 64 days after the second vaccination. Multilevel linear regression models were used to estimate the geometric mean titers (GMT) and the ratios of means (RoM) between groups with adjustment for covariates. Compared with never-smokers (GMT = 118), IgG antibody titers were significantly lower among HTPs users (including those who also smoked cigarettes) (GMT = 105; RoM = 0.89 [95%CI: 0.78-0.99]) and exclusive cigarettes smokers (GMT = 98; RoM = 0.81 [95%CI: 0.71-0.92]). Compared with non-drinkers of alcohol (GMT = 123), alcohol drinkers consuming <1 go/day (GMT = 113; RoM = 0.93 [95%CI: 0.88-0.98]), 1-1.9 go/day (GMT = 104; RoM = 0.85 [95%CI: 0.78-0.93]), and ≥ 2 go/day (GMT = 103; RoM = 0.84 [95%CI: 0.74-0.96]) had significantly lower antibody titers (P for trend<0.01). Spline analysis showed a large reduction of antibody until around 1 go/day of alcohol consumption, and then they gradually decreased. Results suggest that in addition to conventional cigarette smoking and heavy alcohol drinking, HTPs use and moderate alcohol drinking may be predictors of lower immunological response to COVID-19 vaccine.