Achievement of Guideline-Recommended Targets for Secondary Prevention of Cardiovascular Disease in 38 Low-Income and Middle-Income Countries.

BACKGROUND: This study aimed to estimate the prevalence of achieving the secondary prevention targets recommended in the World Health Organization (WHO) guidelines for cardiovascular disease (CVD) in 38 low-income and middle-income countries (LMICs). METHODS: We pooled nationally representative cross-sectional surveys from 38 LMICs between 2013 and 2020. Treatment, metabolic and lifestyle targets were assessed for individuals with a self-reported history of CVD according to WHO's recommendations. Associations between the prevalence of guideline adherence and sociodemographic characteristics were assessed using multivariate Poisson regression models. RESULTS: The pooled sample included 126 106 participants, of whom 9821 (6.8% [95% CI 6.4-7.2]) reported a history of CVD. Overall, the prevalence of achieving treatment targets in patients with CVD was 22.7% (95% CI, 21.0-24.5%) for antihypertensive drugs, 19.6% (17.9-21.4%) for aspirin, and 13.6% (12.0-15.44%) for statins. The prevalence of achieving metabolic targets was 54.9% (52.5-57.3%) for BMI, 39.9% (37.7-42.2%) for blood pressure, 46.1% (43.6-48.6%) for total cholesterol, and 84.9% (83.1-86.5%) for fasting blood glucose. The prevalence of achieving lifestyle targets was 83.2% (81.5-84.7%) for not smoking, 83.1% (81.2-84.9%) for not drinking, 65.5% (63.1-67.7%) for sufficient physical activity and 16.2% (14.5-18.0%) for healthy diet. Only 6.1% (5.1-7.4%) achieved three treatment targets, 16.0% (14.3-17.9%) achieved four metabolic targets, and 6.9% (5.8-8.0%) achieved four lifestyle targets. Upper-middle income countries were better than low-income countries at achieving the treatment, non-drinking and dietary targets. Being younger and female were associated with poorer achievement of metabolic targets. CONCLUSION: In LMICs, achieving the targets recommended in the guideline for treatment, metabolism and healthy lifestyles for patients with CVD is notably low. This highlights an urgent need for effective, systematic secondary prevention strategies to improve CVD management.

Behavioral counseling for cardiovascular disease prevention in 36 low-income and middle-income countries.

BACKGROUND: Given the substantial prevalence of cardiovascular disease (CVD) in low-income and middle-income countries (LMICs), evaluation of behavioral counseling for prevention of CVD is important. METHODS: We pooled nationally representative cross-sectional surveys from 36 LMICs between 2013 and 2020. The population was divided into three groups according to CVD risk: the potential risk group, the risk group and the CVD group. We estimated the prevalence of six types of behavioral counseling among the three groups separately: smoking, salt reduction, fruit and vegetable intake, dietary fat reduction, physical activity and body weight. RESULTS: There were 16,057 (25.4%) in the potential risk group, 43,113 (49.9%) in the risk group, and 7796 (8.6%) in the CVD group. The prevalence of receiving at least four types of counseling in the three groups was 15.6% (95% CI 13.9 to 17.5), 14.9% (95% CI 14.0 to 15.9), and 19.8% (95% CI 17.7 to 22.2), respectively. The lowest prevalence was for tobacco use counseling: 24.5% (95% CI 22.5 to 26.4), 23.2% (95% CI 22.1 to 24.3), and 32.1% (95% CI 29.5 to 34.8), respectively. The prevalence of counseling was higher in upper-middle-income countries than in lower-middle-income countries. Women, older people, those with more education, and those living in urban areas were more likely to receive counseling. CONCLUSION: The prevalence of behavioral counseling for CVD is low in LMICs, especially among potentially at-risk populations and in low-income countries. These findings highlight the current urgent need to improve CVD prevention and management systems to enhance behavioral counseling and intervention.

Association of smoking cessation with airflow obstruction in workers with silicosis: A cohort study.

BACKGROUND: Studies in general population reported a positive association between tobacco smoking and airflow obstruction (AFO), a hallmark of chronic obstructive pulmonary disease (COPD). However, this attempt was less addressed in silica dust-exposed workers. METHODS: This retrospective cohort study consisted of 4481 silicotic workers attending the Pneumoconiosis Clinic during 1981-2019. The lifelong work history and smoking habits of these workers were extracted from medical records. Spirometry was carried out at the diagnosis of silicosis (n = 4177) and reperformed after an average of 9.4 years of follow-up (n = 2648). AFO was defined as forced expiratory volume in one second (FEV1)/force vital capacity (FVC) less than lower limit of normal (LLN). The association of AFO with smoking status was determined using multivariate logistics regression, and the effect of smoking cessation on the development of AFO was evaluated Cox regression. RESULTS: Smoking was significantly associated with AFO (current smokers: OR = 1.92, 95% CI 1.51-2.44; former smokers: OR = 2.09, 95% CI 1.65-2.66). The risk of AFO significantly increased in the first 3 years of quitting smoking (OR = 1.23, 95% CI 1.02-1.47) but decreased afterwards with increasing years of cessation. Smoking cessation reduced the risk of developing AFO no matter before or after the confirmation of silicosis (pre-silicosis cessation: HR = 0.58, 95% CI 0.46-0.74; post-silicosis cessation: HR = 0.62, 95% CI 0.48-0.79). CONCLUSIONS: Smoking cessation significantly reduced the risk of AFO in the workers with silicosis, although the health benefit was not observed until 3 years of abstinence. These findings highlight the importance of early and long-term smoking cessation among silicotic or silica dust-exposed workers.

Association Between Metabolic Syndrome and Mortality: Prospective Cohort Study.

BACKGROUND: Metabolic syndrome (MetS) is a common metabolic disorder that results from the increasing prevalence of obesity, which has been an increasing concern in recent years. Previous evidence indicated that MetS was associated with mortality; however, different definitions of MetS were used. In 2005, the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III updated the definition of MetS, which has since been widely adopted. Therefore, it is necessary to conduct a novel study among other populations and countries with a larger sample size using the updated definition of MetS and death code to examine the association of MetS with all-cause and cause-specific mortality. OBJECTIVE: We aimed to examine the associations of MetS with all-cause and cause-specific mortality. METHODS: A total of 36,414 adults were included in this study, using data from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and the continuous NHANES (1999-2014) in the United States. Death outcomes were ascertained by linkage to National Death Index records through December 31, 2015. MetS was defined by the NCEP ATP III-2005 criterion. Complex survey design factors including sample weights, clustering, and stratification were considered for all analyses with instructions for using NHANES data. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for mortality from all causes, heart disease, diabetes, and cancer. RESULTS: We observed 8494 deaths during the 16.71 years of follow-up. Compared with those without MetS, individuals with MetS were associated with a significantly elevated multiadjusted HR of 1.24 (95% CI 1.16-1.33), 1.44 (95% CI 1.25-1.66), and 5.15 (95% CI 3.15-8.43) for all cause, heart diseases, and diabetes mellitus, respectively, whereas no significant association was found for cancer mortality (HR 1.17, 95% CI 0.95-1.43). CONCLUSIONS: Our study provides additional evidence that MetS and its components are significantly associated with all-cause, heart disease, and diabetes mortality, but not with cancer mortality. Health care professionals should pay more attention to MetS and its individual component.

Association of spirometric restriction with mortality in the silicotics: a cohort study.

BACKGROUND: Restrictive spirometry pattern (RSP), defined as reduced forced vital capacity (FVC) in absence of airflow obstruction (AFO), is associated with increased risk of mortality in general population. However, evidence in the patients with silicosis is limited. This study was aimed to investigate the relationship between RSP and the risk of death in a silicotic cohort. METHOD: This retrospective cohort study used data from the Pneumoconiosis Clinic, Hong Kong Department of Health that containing 4315 patients aged 18-80 years and diagnosed with silicosis during 1981-2019, with a follow-up till 31 December 2019. Spirometry was carried out at the diagnostic examination of silicosis. Lung function categories were classified as normal spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted), RSP only (FEV1/FVC ≥ 0.7, FVC < 80% predicted), AFO only (FEV1/FVC < 0.7, FVC ≥ 80% predicted), and RSP&AFO mixed (FEV1/FVC < 0.7, FVC < 80% predicted). The hazard ratio (HR) and 95% confidence intervals (95% CI) were computed using a Cox proportional hazards model adjusting for age, body mass index, history of tuberculosis, smoking status, pack-years, and radiographic characteristics of silicotic nodules. RESULTS: Among the 4315 patients enrolled in the study, the prevalence of RSP was 24.1% (n = 1038), including 11.0% (n = 473) with RSP only and 13.1% (n = 565) with mixed RSP and AFO. During the follow-up period, a total of 2399 (55.6%) deaths were observed. Compared with the silicotics with normal spirometry, those with RSP only had significantly increased risk of all-cause mortality (HR = 1.63, 95% CI 1.44-1.85) and respiratory-related mortality (HR = 1.56, 95% CI 1.31-1.85). Notably, a higher risk of mortality was observed in silicotics with mixed ventilatory defects of both RSP and AFO (all-cause mortality: HR = 2.22, 95% CI 1.95-2.52; respiratory-related mortality: HR = 2.59, 95% CI 2.18-3.07) than in those with RSP only. CONCLUSION: RSP is significantly associated with increased risk of all-cause and respiratory-related mortality in the silicotics, and patients with mixed restrictive and obstructive ventilatory defect have higher risk of mortality than those with single RSP or AFO. These findings emphasize the importance of recognizing RSP in the occupational settings, especially for the silicotic patients with mixed ventilatory defect.

Efficacy and safety of treatment regimens for patients with metastatic, locally advanced, or recurrent breast cancer carrying BRCA1/BRCA2 pathogenic variants: A network meta-analysis.

Objective: Patients with breast cancer carrying BRCA1 and BRCA2 genetic alterations show poor prognoses. However, the efficacy of pharmacotherapies for patients with advanced breast cancer carrying BRCA1/2 pathogenic variants remains unclear. This study aimed to conduct a network meta-analysis to assess the efficacy and safety of various pharmacotherapies for patients with metastatic, locally advanced, or recurrent breast cancer carrying BRCA1/BRCA2 pathogenic variants. Methods: A literature search was conducted using Embase, PubMed, and Cochrane Library (CENTRAL), from inception to 11th May 2022. The references of included articles were screened to identify relevant literature. This network meta-analysis included patients with metastatic locally advanced or recurrent breast cancer who received pharmacotherapy and carried deleterious variants of BRCA1/2. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed for conducting and reporting this systematic meta-analysis. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was employed to evaluate evidential certainty. Frequentist random-effect model was applied. Results of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and rates of any-grade adverse events were presented. Results: Nine randomized controlled trials were obtained comprising six treatment regimens, including 1912 patients with pathogenic variants of BRCA1 and BRCA2. The orchestration of PARP inhibitors with platinum-based chemotherapy was found to be the most effective with a pooled odds ratio (OR) of 3.52 (95% CI 2.14, 5.78) for ORR; 1.53 (1.34,1.76), 3.05 (1.79, 5.19), and 5.80 (1.42, 23.77) for 3-, 12-, and 24-month PFS, respectively, and 1.04 (1.00, 1.07), 1.76 (1.25, 2.49) and 2.31 (1.41, 3.77) for 3-, 12-, and 36-month OS, respectively compared to those receiving non-platinum-based chemotherapy. However, it posed an elevated risk of some adverse events. Platinum-based chemotherapy alone or PARP inhibitors markedly improved ORR, PFS, and OS compared to non-platinum-based chemotherapy. Interestingly, platinum-based chemotherapy surpassed PARP inhibitors in terms of efficacy. Evidence on programmed death-ligand 1(PD-L1) inhibitors and sacituzumab govitecan (SG) suggested low quality and insignificant results. Conclusions: Among all treatment regimens, PARP inhibitors with platinum exhibited the best efficacy, although with a trade-off of elevated risk of some types of adverse events. Future research on direct comparisons between different treatment regimens specifically targeting patients with breast cancer carrying BRCA1/2 pathogenic variants with a pre-specified adequate sample size is warranted.

DNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer.

BACKGROUND: Few studies have examined epigenetic age acceleration (AA), the difference between DNA methylation (DNAm) predicted age and chronological age, in relation to somatic genomic features in paired cancer and normal tissue, with less work done in non-European populations. In this study, we aimed to examine DNAm age and its associations with breast cancer risk factors, subtypes, somatic genomic profiles including mutation and copy number alterations and other aging markers in breast tissue of Chinese breast cancer (BC) patients from Hong Kong. METHODS: We performed genome-wide DNA methylation profiling of 196 tumor and 188 paired adjacent normal tissue collected from Chinese BC patients in Hong Kong (HKBC) using Illumina MethylationEPIC array. The DNAm age was calculated using Horvath's pan-tissue clock model. Somatic genomic features were based on data from RNA sequencing (RNASeq), whole-exome sequencing (WES), and whole-genome sequencing (WGS). Pearson's correlation (r), Kruskal-Wallis test, and regression models were used to estimate associations of DNAm AA with somatic features and breast cancer risk factors. RESULTS: DNAm age showed a stronger correlation with chronological age in normal (Pearson r = 0.78, P < 2.2e-16) than in tumor tissue (Pearson r = 0.31, P = 7.8e-06). Although overall DNAm age or AA did not vary significantly by tissue within the same individual, luminal A tumors exhibited increased DNAm AA (P = 0.004) while HER2-enriched/basal-like tumors exhibited markedly lower DNAm AA (P = < .0001) compared with paired normal tissue. Consistent with the subtype association, tumor DNAm AA was positively correlated with ESR1 (Pearson r = 0.39, P = 6.3e-06) and PGR (Pearson r = 0.36, P = 2.4e-05) gene expression. In line with this, we found that increasing DNAm AA was associated with higher body mass index (P = 0.039) and earlier age at menarche (P = 0.035), factors that are related to cumulative exposure to estrogen. In contrast, variables indicating extensive genomic instability, such as TP53 somatic mutations, high tumor mutation/copy number alteration burden, and homologous repair deficiency were associated with lower DNAm AA. CONCLUSIONS: Our findings provide additional insights into the complexity of breast tissue aging that is associated with the interaction of hormonal, genomic, and epigenetic mechanisms in an East Asian population.

Regional differences in the contribution of smoking, dietary and cooking behaviours to airflow obstruction in China: A population-based case-control study.

BACKGROUND AND OBJECTIVE: The major contributing risk factors to airflow obstruction (AO) in China remain largely unknown. We examined the environmental and lifestyle risk factors of unrecognized AO in the baseline of a population-based cohort drawn from 115 urban and rural communities across 12 provinces in China. METHODS: Amongst 46,285 adults recruited from 2005 to 2009, 3686 were identified with AO on spirometry (defined by the ratio of forced expiratory volume in the first second to forced vital capacity <0.7) and without known chronic lung disease. These cases were age- and sex-matched to 11,129 controls with normal spirometry and no chronic lung disease from the same community. Conditional multivariable adjusted OR and population attributable fraction (PAF) were calculated for each identified risk factor and their combined effect. RESULTS: Compared to controls, smoking initiation age <20 years (OR 1.22 [95% CI 1.01-1.48]), smoking duration ≥40 years (OR 1.82 [1.50-2.22]), low vegetables (OR 1.86 [1.67-2.07]) and fruits (OR 1.14 [1.02-1.29]) intake, cooking with biomass fuels (OR 2.54 [2.32-2.78]) and poor kitchen ventilation (OR 1.37 [1.19-1.58]) were significantly associated with elevated risks of unrecognized AO. The combined effect of these lifestyle factors significantly elevated the odds by 25 fold (18.6-34.3). The addition of prior tuberculosis and low socioeconomic status further increased the odds to 40.1 (28.2-57.0) and the PAF to 66.7% (51.1-78.1). CONCLUSION: Smoking, unhealthy diet, biomass cooking fuels and low socioeconomic status are strongly associated with AO. Addressing these risk factors could substantially reduce the burden of AO in China.

The role of dietary carotenoids in preventing the development of esophageal squamous cell carcinoma.

Background and aims: Experimental studies showed that carotenoids had anti-carcinogenesis properties, but epidemiological studies on the association between dietary carotenoids and esophageal squamous cell carcinoma (ESCC) risk were limited, and the findings were inconsistent. This study aimed to investigate the roles of intake of dietary carotenoids in the development of ESCC among a rural Chinese population. Methods: A population-based case-control study was conducted in Southwest China. A total of 915 incident ESCC cases and 925 community-based controls were included. A validated food frequency questionnaire with 76-item was adopted to collect information about dietary consumption. Intake of dietary calories and each carotenoid was calculated according to the China food composition tables. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by using logistic regression model, with adjustments for age, gender, body mass index, family cancer history, cigarette smoking, alcohol drinking, education, marital status, prudent pattern score, and total calories. Results: In comparison of the highest with lowest intake quartiles, intake of total carotene (OR: 0.70, 95% CI: 0.52-0.96, Ptrend: 0.024), α-carotene (OR: 0.62, 95% CI: 0.46-0.83, Ptrend: 0.014), ß-carotene (OR: 0.63, 95% CI: 0.46-0.86, P-trend: 0.005), and the sum of lutein and zeaxanthin (OR: 0.41, 95% CI: 0.29-0.56, Ptrend<0.001) was significantly associated with a decreased risk of ESCC after adjustment for confounders. Conclusions: The results indicated that a higher intake of total carotene, α-carotene, ß-carotene, and the sum of lutein and zeaxanthin was associated with a lower risk of ESCC.

Association of Dietary Phytosterols Intake and Survival of Esophageal Squamous Cell Carcinoma: A Prospective Cohort Study.

BACKGROUND: The association of dietary phytosterols intake with survival of esophageal squamous cell carcinoma (ESCC) remains unclear. This study was to examine the effect of dietary phytosterols intake on ESCC survival in a Chinese rural population. METHODS: A total of 942 incident ESCC patients diagnosed between 2011 and 2013 in Yanting area were followed up until March 1st, 2020. Dietary intake five years before ESCC diagnosis was collected using a food frequency questionnaire. The outcome of interest was all-cause mortality. Cox proportional hazards regression model was used to estimate hazard ratio (HR) and 95% confidence intervals (CI). RESULTS: When comparing the highest with lowest intake quartiles, intake of five specific and total phytosterols was not significantly associated with risk of death after adjustment for covariates, the adjusted HR (95% CI) for ß-sitosterol, campesterol, stigmasterol, ß-sitostanol, campestanol and total phytosterols was 0.90 (95% CI: 0.70-1.16), 0.92 (95% CI: 0.71-1.19), 0.86 (95% CI: 0.66-1.12), 0.93 (95% CI: 0.73-1.20), 0.94 (95% CI: 0.72-1.21), 0.89 (95% CI: 0.69-1.15), respectively. CONCLUSION: This study does not find any association between pre-diagnostic phytosterols intake and risk of all-cause mortality among ESCC patients. Further research is required to determine the effect of post-diagnostic phytosterols intake on ESCC survival.

Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy.

AIMS: To examine the incidence of cardiovascular disease (CVD) and mortality in China and in key subpopulations, and to estimate the population-level risks attributable to 12 common modifiable risk factors for each outcome. METHODS AND RESULTS: In this prospective cohort of 47 262 middle-aged participants from 115 urban and rural communities in 12 provinces of China, it was examined how CVD incidence and mortality rates varied by sex, by urban-rural area, and by region. In participants without prior CVD, population-attributable fractions (PAFs) for CVD and for death related to 12 common modifiable risk factors were assessed: four metabolic risk factors (hypertension, diabetes, abdominal obesity, and lipids), four behavioural risk factors (tobacco, alcohol, diet quality, and physical activity), education, depression, grip strength, and household air pollution. The mean age of the cohort was 51.1 years. 58.2% were female, 49.2% were from urban areas, and 59.6% were from the eastern region of China. The median follow-up duration was 11.9 years. The CVD was the leading cause of death in China (36%). The rates of CVD and death were 8.35 and 5.33 per 1000 person-years, respectively, with higher rates in men compared with women and in rural compared with urban areas. Death rates were higher in the central and western regions of China compared with the eastern region. The modifiable risk factors studied collectively contributed to 59% of the PAF for CVD and 56% of the PAF for death in China. Metabolic risk factors accounted for the largest proportion of CVD (PAF of 41.7%), and hypertension was the most important risk factor (25.0%), followed by low education (10.2%), high non-high-density lipoprotein cholesterol (7.8%), and abdominal obesity (6.9%). The largest risk factors for death were hypertension (10.8%), low education (10.5%), poor diet (8.3%), tobacco use (7.5%), and household air pollution (6.1%). CONCLUSION: Both CVD and mortality are higher in men compared with women, and in rural compared with urban areas. Large reductions in CVD could potentially be achieved by controlling metabolic risk factors and improving education. Lowering mortality rates will require strategies addressing a broader range of risk factors.

Risk assessment and prediction for lung cancer among Hong Kong Chinese men.

OBJECTIVE: Most of the previous risk prediction models for lung cancer were developed from smokers, with discriminatory power ranging from 0.57 to 0.72. We constructed an individual risk prediction model for lung cancer among the male general population of Hong Kong. METHODS: Epidemiological data of 1,069 histology confirmed male lung cancer cases and 1,208 community controls were included in this analysis. Residential radon exposure was retrospectively reconstructed based on individual lifetime residential information. Multivariable logistic regression with repeated cross-validation method was used to select optimal risk predictors for each prediction model for different smoking strata. Individual absolute risk for lung cancer was estimated by Gail model. Receiver-operator characteristic curves, area under the curve (AUC) and confusion matrix were evaluated to demonstrate the model performance and ability to differentiate cases from non-cases. RESULTS: Smoking and smoking cessation, education, lung disease history, family history of cancer, residential radon exposure, dietary habits, carcinogens exposure, mask use and dust control in workplace were selected as the risk predictors for lung cancer. The AUC of estimated absolute risk for all lung cancers was 0.735 (95% CI: 0.714-0.756). Using 2.83% as the cutoff point of absolute risk, the predictive accuracy, positive predictive value and negative predictive value were 0.715, 0.818 and 0.674, respectively. CONCLUSION: We developed a risk prediction model with moderate discrimination for lung cancer among Hong Kong males. External validation in other populations is warranted for this model in future studies.

Associations between Preserved Foods and Breast Cancer Risk in Hong Kong Chinese Women.

Preserved food such as cured foods may contain nitrate and nitrite that may contribute to the breast cancer development. Evidence on the associations between these preserved food intakes and risk of breast cancer is sparse. This study aimed to examine the associations between preserved foods (i.e., cured meat, pickled vegetables, canned meat, and canned fruit/vegetables) and breast cancer risk in Hong Kong Chinese women. A total of 1,307 breast cancer cases and 1,050 age-matched controls were recruited from three hospitals during November 2011 through January 2018. We used a standardized questionnaire to collect information on dietary factors, including preserved foods. Unconditional multiple logistic regression was performed to calculate the adjusted odds ratio (AOR) of breast cancer in relation to preserved food with adjustment of potential confounders. We further performed stratified analysis according to the breast cancer biology subtypes. We found that cured meat consumption was significantly associated with the risk of breast cancer [AOR, 1.32; 95% confidence interval 95% (CI), 1.06-1.64]. Compared with no cured meat consumption, cured meat intake ≥ once per week was associated with an AOR of 2.66 (95% CI, 1.38-5.35). Women with canned fruit/vegetable ≥ consumption once per week had a higher risk of breast cancer (OR, 1.19; 95% CI, 1.00-1.41), particularly for the HER2-positive subtypes, but it became borderline after adjustment of confounders. Our study reveals a positive association between consumption of cured meat and breast cancer risk in Chinese population. Cured meat intake might be a potential novel risk factor for breast cancer but this would have to be confirmed by large prospective cohort studies. PREVENTION RELEVANCE: The main finding of this case-control study, an association between cured meat intake and a higher risk of breast cancer in Hong Kong Chinese women, contributes to the growing evidence for population-level health benefits of reducing cured meat consumption.

Dietary intake of monounsaturated and polyunsaturated fatty acids is related to the reduced risk of esophageal squamous cell carcinoma.

BACKGROUND: The relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk. METHODS: This case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model. RESULTS: When comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21-0.51), PUFA (OR: 0.32, 95% CI: 0.20-0.51), and TFA (OR: 0.44, 95% CI: 0.28-0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19-0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC. CONCLUSIONS: This study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.

Night Shift Work, MTNR1B rs10830963 Polymorphism, and Prostate Cancer Risk: Findings from a Prospective, Population-Based Study.

BACKGROUND: The association between night shift work and prostate cancer is controversial. Evidence shows that genetic and environmental factors both contribute to the development of prostate cancer. It is well known that melatonin plays a protective role in prostate cancer. Melatonin receptor 1B gene (MTNR1B) rs10830963 influences the dynamics of melatonin secretion, and night shift work, which disrupts our internal circadian rhythms, also dysregulates the production of melatonin. Therefore, we aimed to examine the interaction between night shift work and rs10830963 polymorphism on prostate cancer. METHODS: This is a prospective cohort study based on UK Biobank that included 133,416 employed male participants. Exposures included night shift work and rs10830963 polymorphism. The primary outcome was the incidence of prostate cancer. Cox regression analysis was used to estimate the association of night shift work and MTNR1B rs10830963 with prostate cancer. RESULTS: A significant interaction was found between night shift work and MTNR1B rs10830963 on the incidence of prostate cancer (P = 0.009). Among non-night shift workers, rs10830963 polymorphism was not significantly associated with the risk of prostate cancer. Among night shift workers, compared with CC carriers, GC carriers had a significantly lower risk of prostate cancer [HR: 0.69; 95% confidence interval (CI): 0.51-0.93], and similar associations were more evident for GG carriers (HR: 0.33; 95% CI: 0.15-0.75). CONCLUSIONS: Compared with MTNR1B rs10830963 CC, carrying allele G may reduce the risk of prostate cancer when exposed to night shift work. IMPACT: These results suggest that rs10830963 G carriers may have a lower risk of prostate cancer when taking night shifts.

Comparison of somatic mutation landscapes in Chinese versus European breast cancer patients.

Recent genomic studies suggest that Asian breast cancer (BC) may have distinct somatic features; however, most comparisons of BC genomic features across populations did not account for differences in age, subtype, and sequencing methods. In this study, we analyzed whole-exome sequencing (WES) data to characterize somatic copy number alterations (SCNAs) and mutation profiles in 98 Hong Kong BC (HKBC) patients and compared with those from The Cancer Genome Atlas of European ancestry (TCGA-EA, N = 686), which had similar distributions of age at diagnosis and PAM50 subtypes as in HKBC. We developed a two-sample Poisson model to compare driver gene selection pressure, which reflects the effect sizes of cancer driver genes, while accounting for differences in sample size, sequencing platforms, depths, and mutation calling methods. We found that somatic mutation and SCNA profiles were overall very similar between HKBC and TCGA-EA. The selection pressure for small insertions and deletions (indels) in GATA3 (false discovery rate (FDR) corrected p < 0.01) and single-nucleotide variants (SNVs) in TP53 (nominal p = 0.02, FDR corrected p = 0.28) was lower in HKBC than in TCGA-EA. Among the 13 signatures of single-base substitutions (SBS) that are common in BC, we found a suggestively higher contribution of SBS18 and a lower contribution of SBS1 in HKBC than in TCGA-EA, while the two APOBEC-induced signatures showed similar prevalence. Our results suggest that the genomic landscape of BC was largely very similar between HKBC and TCGA-EA, despite suggestive differences in some driver genes and mutational signatures that warrant future investigations in large and diverse Asian populations.

Genetically Predicted Circulating Levels of Antioxidants and Risk of Breast and Ovarian Cancer.

Evidence from observational studies for the effects of circulating antioxidants on the risk of breast and ovarian cancer was inconsistent. To elucidate the potential causal association of circulating antioxidants on the risk of breast and ovarian cancer, we carried out a two-sample Mendelian randomization (MR) study. The instrumental variables as proxies of genetic liability to circulating antioxidants were obtained from several published data. Summary-level data of breast and ovarian cancer were obtained from genome-wide association study (GWAS) conducted by the Breast (122,977 cases and 105,974 controls) and the Ovarian (25,509 cases and 40,941 controls) Cancer Association Consortiums. MR analyses were mainly performed using the inverse variance-weighted tests. Sensitivity analyses were further conducted to assess heterogeneity and horizontal pleiotropy. No evidence of causal association between genetically predicted circulating antioxidants and breast cancer and its histotypes was discovered as assessed by absolute levels [ß-carotenoid: OR, 0.98; 95% confidence interval (CI), 0.92-1.05; P = 0.627; lycopene: OR, 0.99; 95% CI, 0.95-1.03; P = 0.532; retinol: OR, 0.87; 95% CI, 0.49-1.55; P = 0.645; ascorbate: OR, 1.00; 95% CI, 0.99-1.00; P = 0.123] and metabolites (α-tocopherol: OR, 0.88; 95% CI, 0.65-1.19; P = 0.394; γ-tocopherol: OR, 1.00; 95% CI, 0.87-1.16; P = 0.978; retinol: OR, 1.02; 95% CI, 1.00-1.04; P = 0.070; ascorbate: OR, 0.99; 95% CI, 0.91-1.06; P = 0.703). Similarly, no beneficial effect of genetic determinants of circulating antioxidants on ovarian cancer and its histotypes was found. Our study might not indicate a protective role of circulating antioxidants on the breast or ovarian cancer risk. PREVENTION RELEVANCE: Although this study does not find that circulating antioxidants are protective against breast and ovarian cancer, it is still possible that a high intake of antioxidant-rich foods containing other potentially beneficial components could be cancer preventative. .

Differences and agreement between two portable hand-held spirometers across diverse community-based populations in the Prospective Urban Rural Epidemiology (PURE) study.

INTRODUCTION: Portable spirometers are commonly used in longitudinal epidemiological studies to measure and track the forced expiratory volume in first second (FEV1) and forced vital capacity (FVC). During the course of the study, it may be necessary to replace spirometers with a different model. This raise questions regarding the comparability of measurements from different devices. We examined the correlation, mean differences and agreement between two different spirometers, across diverse populations and different participant characteristics. METHODS: From June 2015 to Jan 2018, a total of 4,603 adults were enrolled from 628 communities in 18 countries and 7 regions of the world. Each participant performed concurrent measurements from the MicroGP and EasyOne spirometer. Measurements were compared by the intra-class correlation coefficient (ICC) and Bland-Altman method. RESULTS: Approximately 65% of the participants achieved clinically acceptable quality measurements. Overall correlations between paired FEV1 (ICC 0.88 [95% CI 0.87, 0.88]) and FVC (ICC 0.84 [0.83, 0.85]) were high. Mean differences between paired FEV1 (-0.038 L [-0.053, -0.023]) and FVC (0.033 L [0.012, 0.054]) were small. The 95% limits of agreement were wide but unbiased (FEV1 984, -1060; FVC 1460, -1394). Similar findings were observed across regions. The source of variation between spirometers was mainly at the participant level. Older age, higher body mass index, tobacco smoking and known COPD/asthma did not adversely impact on the inter-device variability. Furthermore, there were small and acceptable mean differences between paired FEV1 and FVC z-scores using the Global Lung Initiative normative values, suggesting minimal impact on lung function interpretation. CONCLUSIONS: In this multicenter, diverse community-based cohort study, measurements from two portable spirometers provided good correlation, small and unbiased differences between measurements. These data support their interchangeable use across diverse populations to provide accurate trends in serial lung function measurements in epidemiological studies.

Disease Burden, Risk Factors, and Recent Trends of Liver Cancer: A Global Country-Level Analysis.

BACKGROUND: This study aimed to evaluate the updated disease burden, risk factors, and temporal trends of liver cancer based on age, sex, and country. METHODS: We estimated the incidence of liver cancer and its attribution to hepatitis B virus (HBV) and hepatitis C virus (HCV) in 2018 based on the Global Cancer Observatory and World Health Organization (WHO) Cancer Causes database. We extracted the prevalence of risk factors from the WHO Global Health Observatory to examine the associations by weighted linear regression. The trend analysis used data from the Cancer Incidence in Five Continents and the WHO mortality database from 48 countries. Temporal patterns of incidence and mortality were calculated using average annual percent change (AAPC) by joinpoint regression analysis. RESULTS: The global incidence of liver cancer was (age-standardized rate [ASR]) 9.3 per 100,000 population in 2018, and there was an evident disparity in the incidence related to HBV (ASR 0.2-41.2) and HCV (ASR 0.4-43.5). A higher HCV/HBV-related incidence ratio was associated with a higher level of alcohol consumption (ß 0.49), overweight (ß 0.51), obesity (ß 0.64), elevated cholesterol (ß 0.70), gross domestic product (ß 0.20), and Human Development Index (HDI; ß 0.45). An increasing trend in incidence was identified in many countries, especially for male individuals, population aged ≥50 years, and countries with a higher HCV/HBV-related liver cancer incidence ratio. Countries with the most drastic increase in male incidence were reported in India (AAPC 7.70), Ireland (AAPC 5.60), Sweden (AAPC 5.72), the UK (AAPC 5.59), and Norway (AAPC 4.87). CONCLUSION: We observed an overall increasing trend of liver cancer, especially among male subjects, older individuals, and countries with a higher prevalence of HCV-related liver cancer. More efforts are needed in enhancing lifestyle modifications and accessibility of antiviral treatment for these populations. Future studies should investigate the reasons behind these epidemiological changes.

Joint effect between bisphenol A and alcohol consumption on benign prostatic hyperplasia: A case-control study in Hong Kong Chinese males.

BACKGROUND: Whether bisphenol A (BPA) exposure is a contributing factor to benign prostatic hyperplasia (BPH) remains unclear. This study evaluated the association between chronic BPA exposure and BPH risk, and explored whether this association was modified by alcohol drinking. METHODS: This study included a total of 650 BPH cases and 650 controls recruited from the same hospital in Hong Kong during 2011-2016. Chronic BPA exposure level was estimated by a validated cumulative BPA exposure index (CBPAI). We performed unconditional logistic regression model to examine the association of BPH risk with potential sources of BPA exposure via oral intake and CBPAI. We further tested the interactions between CBPAI and alcohol consumption habits on BPH risk. RESULTS: A positive exposure-response relationship was observed between CBPAI and BPH risk. Frequent BPA exposure via oral intake of foods heated in a plastic box/bag (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.51-8.22), cooling water in a plastic bottle (OR = 2.65, 95% CI: 1.33-5.27), or using a plastic cup to contain hot water (OR = 4.14, 95% CI: 1.02-16.89), was significantly associated with increased BPH risk. Compared with nonalcohol drinkers, alcohol drinkers was insignificantly associated with BPH risk (OR = 1.10, 95% CI: 0.77-1.57), but it demonstrated a more remarkable positive gradient between CBPAI exposure and BPH risk among alcohol drinkers, indicating an additive interaction between CBPAI and alcohol on BPH risk (synergy index = 4.24, 95% CI: 1.21-14.94). CONCLUSIONS: Chronic oral BPA exposure increased BPH risk with a positive exposure-response relationship among Hong Kong Chinese, and alcohol drinking amplified the effect of BPA on BPH. Hence, minimizations of containing food or water/beverage in plastic containers and drinking alcohol are recommended in the community to mitigate BPH risk. Future larger and designated studies are warranted.