Healthy lifestyle, DNA methylation age acceleration, and incident risk of coronary heart disease.

BACKGROUND: DNA methylation clocks emerged as a tool to determine biological aging and have been related to mortality and age-related diseases. Little is known about the association of DNA methylation age (DNAm age) with coronary heart disease (CHD), especially in the Asian population. RESULTS: Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip for 491 incident CHD cases and 489 controls in the prospective China Kadoorie Biobank. We calculated the methylation age using a prediction model developed among Chinese. The correlation between chronological age and DNAm age was 0.90. DNA methylation age acceleration (Δage) was defined as the residual of regressing DNA methylation age on the chronological age. After adjustment for multiple risk factors of CHD and cell type proportion, compared with participants in the bottom quartile of Δage, the OR (95% CI) for CHD was 1.84 (1.17, 2.89) for participants in the top quartile. One SD increment in Δage was associated with 30% increased risk of CHD (OR = 1.30; 95% CI 1.09, 1.56; Ptrend = 0.003). The average number of cigarette equivalents consumed per day and waist-to-hip ratio were positively associated with Δage; red meat consumption was negatively associated with Δage, characterized by accelerated aging in those who never or rarely consumed red meat (all P < 0.05). Further mediation analysis revealed that 10%, 5% and 18% of the CHD risk related to smoking, waist-to-hip ratio and never or rarely red meat consumption was mediated through methylation aging, respectively (all P for mediation effect < 0.05). CONCLUSIONS: We first identified the association between DNAm age acceleration and incident CHD in the Asian population, and provided evidence that unfavorable lifestyle-induced epigenetic aging may play an important part in the underlying pathway to CHD.

Alcohol drinking and risks of total and site-specific cancers in China: A 10-year prospective study of 0.5 million adults.

Alcohol drinking is associated with increased risks of several site-specific cancers, but its role in many other cancers remains inconclusive. Evidence is more limited from China, where cancer rates, drinking patterns and alcohol tolerability differ importantly from Western populations. The prospective China Kadoorie Biobank recruited >512 000 adults aged 30 to 79 years from 10 diverse areas during 2004 to 2008, recording alcohol consumption patterns by a standardised questionnaire. Self-reported alcohol consumption was estimated as grams of pure alcohol per week based on beverage type, amount consumed per occasion and drinking frequency. After 10 years of follow-up, 26 961 individuals developed cancer. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) relating alcohol consumption to incidence of site-specific cancers. Overall, 33% (n = 69 734) of men drank alcohol regularly (ie, ≥weekly) at baseline. Among male current regular drinkers, alcohol intake showed positive dose-response associations with risks of cancers in the oesophagus (655 events; HR = 1.98 [95%CI 1.79-2.18], per 280 g/wk), mouth and throat (236; 1.74 [1.48-2.05]), liver (573; 1.52 [1.31-1.76]), colon-rectum (575; 1.19 [1.00-1.43]), gallbladder (107; 1.60 [1.16-2.22]) and lung (1017; 1.25 [1.10-1.42]), similarly among never- and ever-regular smokers. After adjustment for total alcohol intake, there were greater risks of oesophageal cancer in daily drinkers than nondaily drinkers and of liver cancer when drinking without meals. The risks of oesophageal cancer and lung cancer were greater in men reporting flushing after drinking than not. In this male population, alcohol drinking accounted for 7% of cancer cases. Among women, only 2% drank regularly, with no clear associations between alcohol consumption and cancer risk. Among Chinese men, alcohol drinking is associated with increased risks of cancer at multiple sites, with certain drinking patterns (eg, daily, drinking without meals) and low alcohol tolerance further exacerbating the risks.

Selection of high-risk individuals for esophageal cancer screening: A prediction model of esophageal squamous cell carcinoma based on a multicenter screening cohort in rural China.

The mortality benefit of esophageal squamous cell carcinoma (ESCC) screening has been reported in several studies; however, the results of ESCC screening programs in China are suboptimal. Our study aimed to develop an ESCC risk prediction model to identify high-risk individuals for population-based esophageal cancer screening. In total, 86 745 participants enrolled in a population-based esophageal cancer screening program in rural China between 2007 and 2012 were included in the present study and followed up until December 31, 2015. Models for identifying individuals at risk of ESCC within 3 years were created using logistic regressions. The area under the receiver operating curve (AUC) was determined to estimate the model's overall performance. A total of 298 individuals were diagnosed with ESCC within 3 years after baseline. The model of ESCC included the predictors of age, sex, family history of upper gastrointestinal cancer, smoking status, alarming symptoms of retrosternal pain, back pain or neck pain, consumption of salted food and fresh fruits and disease history of peptic ulcer or esophagitis (AUC of 0.81; 95% confidence interval: 0.78-0.83). Compared to the current prescreening strategy in our program, the cut-off value of 10 in the score-based model could result in 3.11% fewer individuals subjected to endoscopies and present higher sensitivity, slightly higher specificity and lower number needed to screen. This score-based risk prediction model of ESCC based on eight epidemiological risk factors could increase the efficiency of the esophageal cancer screening program in rural China.

Association of cancer awareness levels with the risk of cancer in rural China: A population-based cohort study.

BACKGROUND: Evidence of the effects of cancer prevention knowledge on the risk of developing cancer remains scarce. The objective of this study was to prospectively examine the association of cancer prevention awareness levels with cancer risk in a population-based cancer screening cohort in China. METHODS: This prospective cohort study included 164,341 participants aged 40 to 69 years with no history of cancer and with available information on cancer prevention core knowledge in the Esophageal, Stomach, and Liver Cancer Screening Program. Participants were recruited from 18 rural regions across 4 provinces in China from 2007 to 2014 and were followed until December 31, 2015. The core knowledge of cancer prevention content included 9 items, with a total score ranging from 0 to 100. Cox proportional hazards regression models and restricted cubic spline analysis were used to estimate hazard ratios and 95% CIs. RESULTS: High cancer prevention knowledge scores were inversely associated with the overall risk of cancer (group 4 vs group 1: hazard ratio, 0.669; 95% CI, 0.576-0.776). Subgroup analysis showed that this inverse association could be observed in women, participants with lower educational or income levels, and those without a family history of cancer. Restricted cubic spline analysis exhibited a nonlinear (L-shaped) relation between cancer knowledge scores and cancer risk (overall P < .0001; nonlinear P = .0141). CONCLUSIONS: The main finding of this prospective study was that higher levels of cancer prevention awareness could be associated with a relative reduction in the risk of developing cancer.

Non-linear relationship between sleep duration and metabolic syndrome: A population-based study.

The aims of this study were to evaluate the prevalence of metabolic syndrome (MetS) and explore the association between sleep duration and MetS. This study enrolled 8 272 adults aged 18 years and older from 6 urban and 8 rural areas during 2013 to 2014in Henan China. Participants were interviewed about demographic characteristics, lifestyle factors and medical history, and physical measurements were performed. The relationships between sleep duration and MetS were evaluated and plotted by Restricted Cubic Spline Regression. The mean age was 51.5 years (SD 14.2) and 4 916 (59.4%) were female. The crude prevalence of MetS was 30.3% and the age-standardized rate was 23.6%. Men were more likely to have MetS than women (P = .01). MetS was positively associated with age, education, smoking, drinking, BMI and sleep duration, and seemed irrelevant to occupation and sedentary behavior. In terms of individual component of MetS, high blood pressure was the most prevalent component for both men and women, while the lowest prevalent was high triglycerides in men and for women was low high-density lipoprotein cholesterol (HDL-C). There was a U-shaped relationship between sleep duration and MetS and its components. Sleep duration <6 hours or >9 hours were associated with higher risk of MetS (OR from 1.10 to 2.15). The MetS was prevalent, and more than half of total adult population was suffering from high blood pressure. Sleep duration may be a determinant of metabolic health. Both short (<6 hours) and long sleep duration (>9 hours) was linked to an increased risk of MetS.

Association Between Diabetes and Cause-Specific Mortality in Rural and Urban Areas of China.

Importance: In China, diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes. Objectives: To assess the proportional excess mortality associated with diabetes and estimate the diabetes-related absolute excess mortality in rural and urban areas of China. Design, Setting, and Participants: A 7-year nationwide prospective study of 512 869 adults aged 30 to 79 years from 10 (5 rural and 5 urban) regions in China, who were recruited between June 2004 and July 2008 and were followed up until January 2014. Exposures: Diabetes (previously diagnosed or detected by screening) recorded at baseline. Main Outcomes and Measures: All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratio (RR) comparing individuals with diabetes vs those without diabetes at baseline. Results: Among the 512 869 participants, the mean (SD) age was 51.5 (10.7) years, 59% (n = 302 618) were women, and 5.9% (n = 30 280) had diabetes (4.1% in rural areas, 8.1% in urban areas, 5.8% of men, 6.1% of women, 3.1% had been previously diagnosed, and 2.8% were detected by screening). During 3.64 million person-years of follow-up, there were 24 909 deaths, including 3384 among individuals with diabetes. Compared with adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100 000; adjusted RR, 2.00 [95% CI, 1.93-2.08]), which was higher in rural areas than in urban areas (rural RR, 2.17 [95% CI, 2.07-2.29]; urban RR, 1.83 [95% CI, 1.73-1.94]). Presence of diabetes was associated with increased mortality from ischemic heart disease (3287 deaths; RR, 2.40 [95% CI, 2.19-2.63]), stroke (4444 deaths; RR, 1.98 [95% CI, 1.81-2.17]), chronic liver disease (481 deaths; RR, 2.32 [95% CI, 1.76-3.06]), infections (425 deaths; RR, 2.29 [95% CI, 1.76-2.99]), and cancer of the liver (1325 deaths; RR, 1.54 [95% CI, 1.28-1.86]), pancreas (357 deaths; RR, 1.84 [95% CI, 1.35-2.51]), female breast (217 deaths; RR, 1.84 [95% CI, 1.24-2.74]), and female reproductive system (210 deaths; RR, 1.81 [95% CI, 1.20-2.74]). For chronic kidney disease (365 deaths), the RR was higher in rural areas (18.69 [95% CI, 14.22-24.57]) than in urban areas (6.83 [95% CI, 4.73-9.88]). Among those with diabetes, 10% of all deaths (16% rural; 4% urban) were due to definite or probable diabetic ketoacidosis or coma (408 deaths). Conclusions and Relevance: Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and noncardiovascular diseases. Although diabetes was more common in urban areas, it was associated with greater excess mortality in rural areas.

Esophageal Adenocarcinoma and Its Rare Association with Barrett's Esophagus in Henan, China.

Incidence of esophageal adenocarcinoma (EAC) has increased sharply in Western Europe and United States over the past three decades. Nearly all cases of EAC in the west are thought to be associated with Barrett's esophagus (BE) at the time of diagnosis. Regions in the Henan province of China have one of world's highest incidences of esophageal cancer, yet recent temporal trends in the relative rates of EAC with respect to esophageal squamous-cell carcinoma (ESCC), as well as its association with Barrett's esophagus (BE), have not been reported. In this report, we present large-scale longitudinal clinical and histological data on 5401 esophageal cancers (EC) patients diagnosed during the recent 10-year period (2002-2011) at Henan Cancer Hospital, China. All 217 esophageal adenocarcinoma (EAC) patients from these 5401 EC patients were examined to better understand the relationship between Barrett's esophagus (BE) and EAC. We found that EAC was relatively rare and accounted for approximately 5% of all esophageal cancers each year during 2002-2011. There is no evidence of significant temporal trends in the rate of EAC relative to ESCC. Only 10 out of 217 (4.6%) EAC cases were detected to have any evidence of Barrett's esophagus. This result raises the possibility of a different etiological basis for EAC in China motivating more detailed epidemiological, clinical and molecular characterization of EAC in China in order to better understand the neoplastic development of EAC.

Physical activity and sedentary leisure time and their associations with BMI, waist circumference, and percentage body fat in 0.5 million adults: the China Kadoorie Biobank study.

BACKGROUND: Few large studies in China have investigated total physical activity and sedentary leisure time and their associations with adiposity. OBJECTIVE: We investigated determinants of physical activity and sedentary leisure time and their associations with adiposity in China. DESIGN: A total of 466,605 generally healthy participants (age: 30-79 y, 60% female) in the China Kadoorie Biobank were included in this cross-sectional analysis. Self-reported information on a range of activities was collected by interviewer-administered questionnaire. Physical activity was calculated as metabolic equivalent task hours per day (MET-h/d) spent on work, transportation, housework, and nonsedentary recreation. Sedentary leisure time was quantified as hours per day. Adiposity measures included BMI, waist circumference, and percentage body fat (by bioimpedance analysis). Associations were estimated by linear and logistic regression. RESULTS: The mean physical activity was 22 MET-h/d, and the mean sedentary leisure time was 3.0 h/d. For each sex, physical activity was about one-third lower among professionals/administrators than among factory workers, with intermediate levels for other occupational categories. A 1-SD (14 MET-h/d) greater physical activity was associated with a 0.15-unit (95% CI: 0.14, 0.16) lower BMI (in kg/m(2)), a 0.58-cm (95% CI: 0.55, 0.61) smaller waist circumference, and 0.48 (95% CI: 0.45, 0.50) percentage points less body fat. In contrast, a 1-SD (1.5 h/d) greater sedentary leisure time was associated with a 0.19-unit higher BMI (95% CI: 0.18, 0.20), a 0.57-cm larger waist circumference (95% CI: 0.54, 0.59), and 0.44 (95% CI: 0.42, 0.46) percentage points more body fat. For any given physical activity level, greater sedentary leisure time was associated with a greater prevalence of increased BMI, as was lower physical activity for any given sedentary leisure time. CONCLUSIONS: In adult Chinese, physical activity varies substantially by occupation, and lack of physical activity and excess sedentary leisure time are independently and jointly associated with greater adiposity.