Association between family history with lung cancer incidence and mortality risk in the Asia Cohort Consortium.

Family history of lung cancer (FHLC) has been widely studied but most prospective cohort studies have primarily been conducted in non-Asian countries. We assessed the association between FHLC with risk of lung cancer (LC) incidence and mortality in a population of East Asian individuals. A total of 478,354 participants from 11 population-based cohorts in the Asia Cohort Consortium were included. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7,785 LC incident cases were identified. FHLC (any LC subtype) was associated with an increased risk of LC incidence (HR = 1.45, 95% CI = 1.30-1.63). The positive association was observed in men and women (HR = 1.44, 95% CI = 1.26-1.66 in men; HR = 1.47, 95% CI = 1.22-1.79 in women), and in both never-smokers and ever-smokers (HR = 1.43, 95% CI = 1.18-1.73 in never-smokers; HR = 1.46, 95% CI =1.27-1.67 in ever-smokers). FHLC was associated with an increased risk of lung adenocarcinoma (HR = 1.63, 95% CI: 1.36-1. 94), squamous cell carcinoma (HR = 1.88, 95% CI: 1.46-2.44), and other non-small cell LC (HR = 1.94, 95% CI: 1.02-3.68). However, we found no evidence of significant effect modification by sex, smoking status, and ethnic groups. In conclusion, FHLC was associated with increased risk of LC incidence and mortality, and the associations remained consistent regardless of sex, smoking status and ethnic groups among the East Asian population.

Household air pollution disparities between socioeconomic groups in Chicago.

Purpose: To assess household air pollution levels in urban Chicago households and examine how socioeconomic factors influence these levels. Methods: We deployed wireless air monitoring devices to 244 households in a diverse population in Chicago to continuously record household fine particulate matter (PM2.5) concentration. We calculated hourly average PM2.5 concentration in a 24-hour cycle. Four factors-race, household income, area deprivation, and exposure to smoking-were considered in this study. Results: A total of 93085 h of exposure data were recorded. The average household PM2.5 concentration was 43.8 µg m-3. We observed a significant difference in the average household PM2.5 concentrations between Black/African American and non-Black/African American households (46.3 versus 31.6 µg m-3), between high-income and low-income households (18.2 versus 52.5 µg m-3), and between smoking and non-smoking households (69.7 versus 29.0 µg m-3). However, no significant difference was observed between households in less and more deprived areas (43.7 versus 43.0 µg m-3). Implications: Household air pollution levels in Chicago households are much higher than the recommended level, challenging the hypothesis that household air quality is adequate for populations in high income nations. Our results indicate that it is the personal characteristics of participants, rather than the macro environments, that lead to observed differences in household air pollution.

Contextual Deprivation, Race and Ethnicity, and Income in Air Pollution and Cardiovascular Disease.

Importance: Socioeconomically disadvantaged subpopulations are more vulnerable to fine particulate matter (PM2.5) exposure. However, as prior studies focused on individual-level socioeconomic characteristics, how contextual deprivation modifies the association of PM2.5 exposure with cardiovascular health remains unclear. Objective: To assess disparities in PM2.5 exposure association with cardiovascular disease among subpopulations defined by different socioeconomic characteristics. Design, Setting, and Participants: This cohort study used longitudinal data on participants with electronic health records (EHRs) from the All of Us Research Program between calendar years 2016 and 2022. Statistical analysis was performed from September 25, 2023, through February 23, 2024. Exposure: Satellite-derived 5-year mean PM2.5 exposure at the 3-digit zip code level according to participants' residential address. Main Outcome and Measures: Incident myocardial infarction (MI) and stroke were obtained from the EHRs. Stratified Cox proportional hazards regression models were used to estimate the hazard ratio (HR) between PM2.5 exposure and incident MI or stroke. We evaluated subpopulations defined by 3 socioeconomic characteristics: contextual deprivation (less deprived, more deprived), annual household income (≥$50 000, <$50 000), and race and ethnicity (non-Hispanic Black, non-Hispanic White). We calculated the ratio of HRs (RHR) to quantify disparities between these subpopulations. Results: A total of 210 554 participants were analyzed (40% age >60 years; 59.4% female; 16.7% Hispanic, 19.4% Non-Hispanic Black, 56.1% Non-Hispanic White, 7.9% other [American Indian, Asian, more than 1 race and ethnicity]), among whom 954 MI and 1407 stroke cases were identified. Higher PM2.5 levels were associated with higher MI and stroke risks. However, disadvantaged groups (more deprived, income <$50 000 per year, Black race) were more vulnerable to high PM2.5 levels. The disparities were most pronounced between groups defined by contextual deprivation. For instance, increasing PM2.5 from 6 to 10 µg/m3, the HR for stroke was 1.13 (95% CI, 0.85-1.51) in the less-deprived vs 2.57 (95% CI, 2.06-3.21) in the more-deprived cohort; 1.46 (95% CI, 1.07-2.01) in the $50 000 or more per year vs 2.27 (95% CI, 1.73-2.97) in the under $50 000 per year cohort; and 1.70 (95% CI, 1.35-2.16) in White individuals vs 2.76 (95% CI, 1.89-4.02) in Black individuals. The RHR was highest for contextual deprivation (2.27; 95% CI, 1.59-3.24), compared with income (1.55; 95% CI, 1.05-2.29) and race and ethnicity (1.62; 95% CI, 1.02-2.58). Conclusions and Relevance: In this cohort study, while individual race and ethnicity and income remained crucial in the adverse association of PM2.5 with cardiovascular risks, contextual deprivation was a more robust socioeconomic characteristic modifying the association of PM2.5 exposure.

Differing associations of PM2.5 exposure with systolic and diastolic blood pressures across exposure durations in a predominantly non-Hispanic Black cohort.

Environmental health research has suggested that fine particulate matter (PM2.5) exposure can lead to high blood pressures, but it is unclear whether the impacts remain the same for systolic and diastolic blood pressures (SBP and DBP). This study aimed to examine whether the effects of PM2.5 exposure on SBP and DBP differ using data from a predominantly non-Hispanic Black cohort collected between 2013 and 2019 in the US. PM2.5 exposure was assessed based on a satellite-derived model across exposure durations from 1 to 36 months. The average PM2.5 exposure level was between 9.5 and 9.8 µg/m3 from 1 through 36 months. Mixed effects models were used to estimate the association of PM2.5 with SBP, DBP, and related hypertension types, adjusted for potential confounders. A total of 6381 participants were included. PM2.5 exposure was positively associated with both SBP and DBP. The association magnitudes depended on exposure durations. The association with SBP was null at the 1-month duration (ß = 0.05, 95% CI: - 0.23, 0.33), strengthened as duration increased, and plateaued at the 24-month duration (ß = 1.14, 95% CI: 0.54, 1.73). The association with DBP started with ß = 0.29 (95% CI: 0.11, 0.47) at the 1-month duration, and plateaued at the 12-month duration (ß = 1.61, 95% CI: 1.23, 1.99). PM2.5 was associated with isolated diastolic hypertension (12-month duration: odds ratio = 1.20, 95% CI: 1.07, 1.34) and systolic-diastolic hypertension (12-month duration: odds ratio = 1.18, 95% CI: 1.10, 1.26), but not with isolated systolic hypertension. The findings suggest DBP is more sensitive to PM2.5 exposure and support differing effects of PM2.5 exposure on SBP and DBP. As elevation of SBP and DBP differentially predict CVD outcomes, this finding is relevant for prevention and treatment.

Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia.

Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

Association of KRAS Mutation and Gene Pathways in Colorectal Carcinoma: A Transcriptome- and Methylome-Wide Study and Potential Implications for Therapy.

Kirsten Rat Sarcoma (KRAS) is the most commonly mutated oncogene in colorectal carcinoma (CRC). We have previously reported the interactions between microsatellite instability (MSI), DNA promoter methylation, and gene expression. In this study, we looked for associations between KRAS mutation, gene expression, and methylation that may help with precision medicine. Genome-wide gene expression and DNA methylation were done in paired CRC tumor and surrounding healthy tissues. The results suggested that (a) the magnitude of dysregulation of many major gene pathways in CRC was significantly greater in patients with the KRAS mutation, (b) the up- and down-regulation of these dysregulated gene pathways could be correlated with the corresponding hypo- and hyper-methylation, and (c) the up-regulation of CDKN2A was more pronounced in tumors with the KRAS mutation. A recent cell line study showed that there were higher CDKN2A levels in 5-FU-resistant CRC cells and that these could be down-regulated by Villosol. Our findings suggest the possibility of a better response to anti-CDKN2A therapy with Villosol in KRAS-mutant CRC. Also, the more marked up-regulation of genes in the proteasome pathway in CRC tissue, especially with the KRAS mutation and MSI, may suggest a potential role of a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) in selected CRC patients if necessary.

Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries.

BACKGROUND: Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches. METHODS: This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity. FINDINGS: Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I2=61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I2=59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I2=68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes. INTERPRETATION: The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines. FUNDING: The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Assessment of unmeasured confounding in the association between perceived discrimination and mental health in a predominantly African American cohort using g-estimation.

BACKGROUND: Perceived discrimination in health care settings can have adverse consequences on mental health in minority groups. However, the association between perceived discrimination and mental health is prone to unmeasured confounding. The study aims to quantitatively evaluate the influence of unmeasured confounding in this association, using g-estimation. METHODS: In a predominantly African American cohort, we applied g-estimation to estimate the association between perceived discrimination and mental health, adjusted and unadjusted for measured confounders. Mental health was measured using clinical diagnoses of anxiety, depression and bipolar disorder. Perceived discrimination was measured as the number of patient-reported discrimination events in health care settings. Measured confounders included demographic, socioeconomic, residential and health characteristics. The influence of confounding was denoted as α1 from g-estimation. We compared α1 for measured and unmeasured confounding. RESULTS: Strong associations between perceived discrimination in health care settings and mental health outcomes were observed. For anxiety, the odds ratio (95% confidence interval) unadjusted and adjusted for measured confounders were 1.30 (1.21, 1.39) and 1.26 (1.17, 1.36), respectively. The α1 for measured confounding was -0.066. Unmeasured confounding with α1=0.200, which was over three times that of measured confounding, corresponds to an odds ratio of 1.12 (1.01, 1.24). Similar results were observed for other mental health outcomes. CONCLUSION: Compared with measured confounding, unmeasured that was three times measured confounding was not enough to explain away the association between perceived discrimination and mental health, suggesting that this association is robust to unmeasured confounding. This study provides a novel framework to quantitatively evaluate unmeasured confounding.

Exposure to metal mixtures and telomere length in Bangladeshi children.

Telomere length is associated with chronic diseases and in younger populations, may represent a biomarker of disease susceptibility. As growing evidence suggests that environmental factors, including metals, may impact telomere length, we investigated the association between 17 metals measured in toenail samples and leukocyte relative telomere length (RTL), among 472 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort. In single exposure linear regression models, a doubling of arsenic (As) and mercury (Hg) (µg/g) were associated with a -0.21 (95%CI: -0.032, -0.010; p=0.0005) and -0.017 (95%CI: -0.029, -0.004; p=0.006) difference in RTL, respectively. In Bayesian Kernel Machine Regression (BKMR) mixture models, the overall metal mixture was inversely associated with RTL (P-for-trend <0.001). Negative associations with RTL were observed with both log2-As and log2-Hg, while an inverted U-shaped association was observed for log2-zinc (Zn) with RTL. We found little evidence of interaction among metals. Sex-stratification identified stronger associations of the overall mixture and log2-As with RTL among females, compared to males. Our study suggests that As and Hg may independently influence RTL in mid-childhood. Further studies are needed to investigate potential long-term impacts of metal-associated telomere shortening in childhood on health outcomes in adult life.

Molecular Profiling and the Interaction of Somatic Mutations with Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) in a Population Exposed to Arsenic.

Exposure to inorganic arsenic (As) is recognized as a risk factor for non-melanoma skin cancer (NMSC). We followed up with 7000 adults for 6 years who were exposed to As. During follow-up, 2.2% of the males and 1.3% of the females developed basal cell carcinoma (BCC), while 0.4% of the male and 0.2% of the female participants developed squamous cell carcinoma (SCC). Using a panel of more than 400 cancer-related genes, we detected somatic mutations (SMs) in the first 32 NMSC samples (BCC = 26 and SCC = 6) by comparing paired (tissue-blood) samples from the same individual and then comparing them to the SM in healthy skin tissue from 16 participants. We identified (a) a list of NMSC-associated SMs, (b) SMs present in both NMSC and healthy skin, and (c) SMs found only in healthy skin. We also demonstrate that the presence of non-synonymous SMs in the top mutated genes (like PTCH1, NOTCH1, SYNE1, PKHD1 in BCC and TP53 in SCC) significantly affects the magnitude of differential expressions of major genes and gene pathways (basal cell carcinoma pathways, NOTCH signaling, IL-17 signaling, p53 signaling, Wnt signaling pathway). These findings may help select groups of patients for targeted therapy, like hedgehog signaling inhibitors, IL17 inhibitors, etc., in the future.

Long-term exposure to ambient air pollution and measures of central hemodynamics and arterial stiffness among multiethnic Chicago residents.

OBJECTIVES: To examine whether long-term air pollution exposure is associated with central hemodynamic and brachial artery stiffness parameters. METHODS: We assessed central hemodynamic parameters including central blood pressure, cardiac parameters, systemic vascular compliance and resistance, and brachial artery stiffness measures [including brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR)] using waveform analysis of the arterial pressure signals obtained from a standard cuff sphygmomanometer (DynaPulse2000A, San Diego, CA). The long-term exposures to particles with an aerodynamic diameter < 2.5 µm (PM2.5) and nitrogen dioxide (NO2) for the 3-year periods prior to enrollment were estimated at residential addresses using fine-scale intra-urban spatiotemporal models. Linear mixed models adjusted for potential confounders were used to examine associations between air pollution exposures and health outcomes. RESULTS: The cross-sectional study included 2,387 Chicago residents (76% African Americans) enrolled in the ChicagO Multiethnic Prevention And Surveillance Study (COMPASS) during 2013-2018 with validated address information, PM2.5 or NO2, key covariates, and hemodynamics measurements. We observed long-term concentrations of PM2.5 and NO2 to be positively associated with central systolic, pulse pressure and BAR, and negatively associated with BAD, and BAC after adjusting for relevant covariates. A 1-µg/m3 increment in preceding 3-year exposures to PM2.5 was associated with 1.8 mmHg higher central systolic (95% CI: 0.98, 4.16), 1.0 mmHg higher central pulse pressure (95% CI: 0.42, 2.87), a 0.56%mmHg lower BAD (95% CI: -0.81, -0.30), and a 0.009 mL/mmHg lower BAC (95% CI: -0.01, -0.01). CONCLUSION: This population-based study provides evidence that long-term exposures to PM2.5 and NO2 is related to central BP and arterial stiffness parameters, especially among African Americans.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Understanding of cervical cancer, acceptability of HPV self-collection, and prevalence of HPV in a semi-urban setting in Bangladesh.

Human Papillomavirus (HPV) self-sampling has been implemented successfully as an alternative to traditional forms of cervical cancer screening in low-resource settings. Through Bangladesh's current national cervical cancer screening program, only about 10% of the at-risk population is reached. Thus, Bangladesh is an ideal setting to consider HPV self-sampling to improve cervical cancer prevention efforts. However, the feasibility and acceptability of HPV self-sampling has not been evaluated in Bangladesh. We aimed to understand levels of HPV and cervical cancer knowledge and to evaluate the feasibility and acceptability of HPV self-sampling for cervical cancer screening in a semi-urban Bangladeshi community. Participants were recruited from a local clinic; 164 women completed a cross-sectional questionnaire about attitudes towards screening, and cervical cancer and HPV risk factor knowledge, and provided self-collected cervical samples for high-risk HPV testing. Of the participants, 4.3% tested positive for high-risk HPV and were referred for appropriate follow-up care. Nearly all participants had heard of cervical cancer, though specific knowledge was quite low. Self-sampling for high-risk HPV testing had high rates of acceptability, high rates of convenience, and very little discomfort and embarrassment reported in this study population, making implementing HPV self-sampling as a form of cervical cancer screening in Bangladesh appear feasible.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Association of Microsatellite Instability and Gene Expression Profile in Colorectal Carcinoma and Potential Implications for Therapy.

Background and Objective: In sporadic colorectal carcinomas (CRC), microsatellite instability (MSI) pathways play important roles. Previously, we showed differences in DNA methylation patterns in microsatellite stable (MSS) colorectal carcinomas and MSI-CRC. In the current study, we explore the similarities and differences in gene expression profiles in MSS and MSI at the gene level and at the pathway level to better understand CRC pathogenesis and/or the potential for therapeutic opportunities. Material and Methods: Seventy-one CRC patients (MSI = 18, MSS = 53) were studied. Paired tumor and adjacent normal tissues were used for genome-wide gene expression assays. Result: At the gene level, we compared the list of differentially expressed genes (fold change (FC) ≥ 3 and FDR < 0.05) in tumor tissues compared to corresponding normal tissue in CRC patients with MSI tumors (190 genes) and MSS tumors (129 genes). Of these, 107 genes overlapped. The list of genes that were differentially expressed in MSI tumors only showed enrichment predominantly in two broad categories of pathways-(a) Inflammation-related pathways including the interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, chemokine signaling, nuclear factor kappa B (NFκB) signaling, and cytokine-cytokine interactions, and (b) metabolism-related pathways, including retinol metabolism, steroid hormone biosynthesis, drug metabolism, pentose and glucoronate interconversions, and ascorbate and aldarate metabolism. The genes in inflammation-related pathways were up-regulated whereas genes in metabolism-related pathways were down-regulated in MSI tumor tissue. Pathway-level analysis also revealed similar results confirming the gene enrichment findings. For example, the 150 genes involved in the IL-17 signaling pathway were on average up-regulated by 1.19 fold (CI 1.16-1.21) in MSI compared to 1.14 fold (CI 1.13-1.16) in MSS patients (interaction p = 0.0009). Conclusions: We document an association between MSI status and differential gene expression that broadens our understanding of CRC pathogenesis. Furthermore, targeting one or more of these dysregulated pathways could provide the basis for improved therapies for MSI and MSS CRC.

Uterine Fibroid Prevalence in a Predominantly Black, Chicago-Based Cohort.

(1) Objectives: To investigate the effect of individual-level, neighborhood, and environmental variables on uterine fibroid (UF) prevalence in a Chicago-based cohort. (2) Methods: Data from the Chicago Multiethnic Prevention and Surveillance Study (COMPASS) were analyzed. Individual-level variables were obtained from questionnaires, neighborhood variables from the Chicago Health Atlas, and environmental variables from NASA satellite ambient air exposure levels. The Shapiro-Wilk test, logistic regression models, and Spearman's correlations were used to evaluate the association of variables to UF diagnosis. (3) Results: We analyzed 602 participants (mean age: 50.3 ± 12.3) who responded to a question about UF diagnosis. More Black than White participants had a UF diagnosis (OR, 1.32; 95% CI, 0.62-2.79). We observed non-significant trends between individual-level and neighborhood variables and UF diagnosis. Ambient air pollutants, PM2.5, and DSLPM were protective against UF diagnosis (OR 0.20, CI: 0.04-0.97: OR 0.33, CI: 0.13-0.87). (4) Conclusions: Associations observed within a sample in a specific geographic area may not be generalizable and must be interpreted cautiously.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Patterns of common illness and injury of readymade garment workers and a review of safety practices in Bangladesh.

BACKGROUND: Readymade garment workers globally experience distinctive vulnerabilities at the workplace. The situation is worse in many developing countries. However, there is a lack of scientific evidence about the health and safety of garment workers in the workplace. OBJECTIVE: The objective of this study was to examine the patterns of illness and injury of garment workers, factory level health safety policies and programs, and views and perception of management staff at factories in Bangladesh. METHODS: This mixed-method study was conducted among garment workers and management level staff between January 2018 and April 2019. We extracted 4000 health records of the workers who attended primary health care centers of the factories and conducted 11 key informant interviews using qualitative method from different management-level staff. RESULTS: Half of the workers (51.0%) were working in the sewing section following 12.8% in quality control and 12.3% in the laundry section. A review of the medical records showed that peptic ulcer diseases (PUDs) (19.2%), fever (11.7%), loose motion (10.3%), and headache (9.4%). Needle injury was uncommon for taking medical care. Occupational safety and health management, safe drinking water, access to maternity leave and other facilities were better in large and medium factories compared with those in small factories. CONCLUSIONS: Although the readymade garments sector is one of the largest sources of foreign currency revenue earnings in Bangladesh, occupational health and safety issues of workers remain a big concern. Thus, support from the government needs more focus on the health and safety of workers.