Associations of long-term joint exposure to various ambient air pollutants with all-cause and cause-specific mortality: evidence from a large population-based cohort study.

The association between long-term joint exposure to all kinds of ambient air pollutants and the risk of mortality is not known. Our study prospectively assessed the joint associations of various air pollutants with cause-specific and all-cause mortality risk and identified potential modifying factors affecting these associations. A total of 400,259 individuals aged 40-70 years were included in this study. Information on PM10, PM2.5-10, PM2.5, NO2, and NOx was collected. A weighted air pollution score was calculated to assess joint exposure to the above air pollutants. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During a median of 12.0 years (4,733,495 person-years) of follow-up, 21,612 deaths were recorded, including 7097 deaths from cardiovascular disease and 11,557 deaths from cancer. The adjusted HRs of all-cause mortality were 1.39 (95% CI: 1.29-1.50), 1.86 (95% CI: 1.63-2.13), 1.12 (95% CI: 1.10-1.14), and 1.04 (95% CI: 1.03-1.05) for every 10-ug/m3 increase in PM10, PM2.5, NO2, and NOx, respectively. The adjusted HRs associated with the air pollution score (the highest quintile versus the lowest quintile) were 1.24 (95% CI: 1.19-1.30) for all-cause mortality, 1.33 (95% CI: 1.23-1.43) for cardiovascular mortality, and 1.16 (95% CI: 1.09-1.23) for cancer mortality. Furthermore, we found that the air pollution score was associated with a linear dose-response increase in mortality risk (all P for linearity < 0.001). The findings highlight the importance of a comprehensive assessment of various air pollutants.

Serum 25-hydroxyvitamin D concentrations and colorectal cancer incidence in adults with type 2 diabetes.

BACKGROUND: To examine the association of serum 25-hydroxyvitamin D (25[OH]D) with colorectal cancer (CRC) risk in adults with type 2 diabetes (T2D). METHODS: Using UK Biobank data, this study included 18,453 adults with T2D. Serum 25(OH)D concentrations were determined by the chemiluminescent immunoassay method. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC outcomes. RESULTS: During a median follow-up of 8.8 years, there were 284 incident CRC cases. Compared with adults with serum 25(OH)D concentrations <25.0 nmol/L, the adjusted HRs (95% CIs) for lower to higher serum 25(OH)D concentrations (25.0 to <50.0, 50.0 to <75.0, and ≥75.0 nmol/L) were 0.61 (0.46-0.82), 0.50 (0.34-0.74), and 0.53 (0.30-0.94), respectively (Ptrend = 0.001). The risk of CRC decreased by 19.0% for per 1-SD increment in serum 25(OH)D concentrations. A nonlinear association of serum 25(OH)D concentrations with CRC risk was observed using a restricted cubic spline analysis (P nonlinearity = 0.002). CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly and nonlinearly associated with a lower risk of CRC. These findings highlight the potential benefits of maintaining adequate vitamin D levels in CRC prevention among adults with T2D.

Habitual fish oil supplementation and incident chronic obstructive pulmonary disease: Data from a prospective cohort study.

BACKGROUND: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear. OBJECTIVE: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition. METHODS: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms. RESULTS: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings. CONCLUSIONS: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Association of Combined Lifestyle and Polygenetic Risk with Incidence of Venous Thromboembolism: A Large Population-Based Cohort Study.

As one of the fatal complications, venous thromboembolism (VTE) is associated with increased mortality. However, the combined effects of adopting multiple healthy lifestyles have not been firmly demonstrated. This study was to evaluate the association of combined healthy lifestyles and genetic risk factors with VTE and to investigate their interaction. A prospective cohort study from UK Biobank with a total of 442,963 men and women aged between 38 to 73 years were recruited from 2006 to 2010 and followed up through 2017 or 2018. A polygenic risk score was constructed and a weighted healthy lifestyle score, including no current smoking, regular physical exercises, healthy diet, and healthy body mass index, was categorized. During a median follow-up 9.0 years (3,912,396 person-years), there were 6,736 (172 per 100,000 person-years) incident VTE cases recorded. Among the participants with an unfavorable lifestyle, 1.80% developed VTE, versus 1.03% of the participants with a favorable lifestyle (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.48-1.68). Of the participants with high genetic risk, 2.42% developed VTE, versus 0.97% of the participants with low genetic risk (HR: 2.60; 95% CI: 2.39-2.81). Moreover, of the participants with high genetic risk and unfavorable lifestyle, 2.90% developed VTE, versus 0.66% of the participants with low genetic risk and favorable lifestyle (HR: 4.09; 95% CI: 3.48-4.79). No significant interaction between genetic risk and lifestyle factors was observed (p for interaction = 0.727). An unfavorable lifestyle was associated with a substantially higher risk of VTE, regardless of the genetic risk strata.

Association of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption With All-Cause and Cause-Specific Mortality : A Large Prospective Cohort Study.

BACKGROUND: Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without. OBJECTIVE: To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: Data were extracted from the UK Biobank. PARTICIPANTS: A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018. MEASUREMENTS: Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated. RESULTS: During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (>0 to 1.5, >1.5 to 2.5, >2.5 to 3.5, >3.5 to 4.5, and >4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee. LIMITATION: Exposure assessed at baseline might not capture changes in intake over time. CONCLUSION: Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.

Association of smoking and polygenic risk with the incidence of lung cancer: a prospective cohort study.

BACKGROUND: Genetic variation increases the risk of lung cancer, but the extent to which smoking amplifies this effect remains unknown. Therefore, we aimed to investigate the risk of lung cancer in people with different genetic risks and smoking habits. METHODS: This prospective cohort study included 345,794 European ancestry participants from the UK Biobank and followed up for 7.2 [6.5-7.8] years. RESULTS: Overall, 26.2% of the participants were former smokers, and 9.8% were current smokers. During follow-up, 1687 (0.49%) participants developed lung cancer. High genetic risk and smoking were independently associated with an increased risk of incident lung cancer. Compared with never-smokers, HR per standard deviation of the PRS increase was 1.16 (95% CI, 1.11-1.22), and HR of heavy smokers (≥40 pack-years) was 17.89 (95% CI, 15.31-20.91). There were no significant interactions between the PRS and the smoking status or pack-years. Population-attributable fraction analysis showed that smoking cessation might prevent 76.4% of new lung cancers. CONCLUSIONS: Both high genetic risk and smoking were independently associated with higher lung cancer risk, but the increased risk of smoking was much more significant than heredity. The combination of traditional risk factors and additional PRS provides realistic application prospects for precise prevention.

Associations Between High-Sensitivity C-Reactive Protein and All-Cause Mortality Among Oldest-Old in Chinese Longevity Areas: A Community-Based Cohort Study.

BACKGROUND: The association between high-sensitivity C-reactive protein (hsCRP) levels and all-cause mortality for the oldest-old (aged 80 years or older) remains unclear. We aimed to investigate the associations between hsCRP concentrations and the risks of all-cause mortality, and further identify the potential modifying factors affecting these associations among the oldest-old. METHODS: This prospective, community-based cohort study included 2,206 participants aged 80 years or older (median age 93.0 years) from the Healthy Aging and Biomarkers Cohort Study. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (95% CIs) for all-cause mortality according to hsCRP quartiles and recommendation for relative risk categories of hsCRP levels (< 1.0, 1.0-3.0, and > 3.0 mg/L), with adjustment for sociodemographic information, lifestyle, physical examination, medical history, and other potential confounders. RESULTS: During a median follow-up period of 3.1 years (IQR: 1.6-3.9 years), 1,106 deaths were verified. After full adjustment for potential confounders, a higher hsCRP concentration was positively associated with an increased risk of all-cause mortality (P for trend < 0.001). Compared with the lowest quartile, the fully adjusted HRs of the second, third, and fourth quartiles were 1.17 (95% CI: 0.94, 1.46), 1.28 (95% CI: 1.01, 1.61), and 1.49 (95% CI: 1.20, 1.87), respectively. The association of hsCRP with all-cause mortality was modified by smoking status (P for interaction = 0.011), an increased risk of hsCRP with all-cause mortality showed among non-current smokers (HR: 1.17; 95% CI: 1.07, 1.28), but no significance was observed in current smokers (HR: 0.83; 95% CI: 0.66, 1.18). CONCLUSIONS: Our study indicated that elevated hsCRP concentrations were associated with a higher risk of all-cause mortality among Chinese oldest-old. Future studies investigating additional factors of disease and aging processes are needed to obtain a better understanding of the mechanisms.

Glucosamine use, smoking and risk of incident chronic obstructive pulmonary disease: a large prospective cohort study.

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40-69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29-9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

Associations of plasma high-sensitivity C-reactive protein concentrations with all-cause and cause-specific mortality among middle-aged and elderly individuals.

BACKGROUND: The association of high-sensitivity C-reactive protein (hsCRP) with mortality is controversial. We aimed to investigate the associations of hsCRP concentrations with the risks of all-cause and cause-specific mortality and identify potential modifying factors affecting these associations among middle-aged and elderly individuals. METHODS: This community-based prospective cohort study included 14,220 participants aged 50+ years (mean age: 64.9 years) from the Health and Retirement Study. Cox proportional hazard models were employed to estimate the associations between the hsCRP concentrations and the risk of all-cause and cause-specific mortality with adjustment for sociodemographic and lifestyle factors, self-reported medical history, and other potential confounders. RESULTS: In total, 1730 all-cause deaths were recorded, including 725 cardiovascular- and 417 cancer-related deaths, after an 80,572 person-year follow-up (median: 6.4 years; range: 3.6-8.1 years). The comparisons of the groups with the highest (quartile 4) and lowest (quartile 1) hsCRP concentrations revealed that the adjusted hazard ratios and 95% confidence intervals were 1.50 (1.31-1.72) for all-cause mortality, 1.44 (1.13-1.82) for cardiovascular mortality, and 1.67 (1.23-2.26) for cancer mortality. The associations between high hsCRP concentrations and the risks of all-cause, cardiovascular, and cancer mortality were similar in the men and women (P for interaction > 0.05). CONCLUSIONS: Among middle-aged and older individuals, elevated hsCRP concentration could increase the risk of all-cause, cardiovascular, and cancer mortality in men and women.

Glycated Hemoglobin and All-Cause and Cause-Specific Mortality Among Adults With and Without Diabetes.

CONTEXT: The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear. OBJECTIVE: To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes. DESIGN, SETTING, AND PATIENTS: This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality. RESULTS: A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was <5.6% or >7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was <5.0%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 5.4%. However, we did not observe a statistically significant elevated risk of all-cause mortality above an HbA1c level of 5.4%. CONCLUSIONS: A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.

Prevalence of human papillomavirus and Epstein-Barr virus in salivary gland diseases.

OBJECTIVE: The roles of human papillomavirus (HPV) and Epstein-Barr virus (EBV) in head and neck neoplasms have been well reported, but little is known about their relationship with salivary gland tumours. This study investigated the presence of HPV and EBV in salivary gland diseases. METHODS: The presence of HPV 16/18 and EBV was analysed in archival pathological specimens collected from patients who had undergone surgery for salivary gland diseases. HPV 16/18 DNA was detected using nested polymerase chain reaction (PCR) and further confirmed with immunohistochemistry. EBV DNA was detected using real-time PCR. RESULTS: A total of 61 pathological specimens were examined: 39.5% (15/38) of pleomorphic adenomas, 33.3% (3/9) of Warthin's tumours, 33.3% (one of 3) of mucoepidermoid carcinomas, and 25.0% (one of 4) of benign lymphoepithelial lesions were positive for high-risk HPV 16/18. Only two Warthin's tumours were positive for EBV. CONCLUSION: The infectious nature of salivary gland neoplasms was revealed by the high prevalence of HPV infection, and the specific presence of EBV in Warthin's tumours, suggesting a potential role for HPV and EBV in salivary gland diseases.

[Insulin promotes proliferation of skeletal myoblast cells through PI3K/Akt and MEK/ERK pathways in rats].

The present study was to explore the effects of insulin on proliferation of skeletal myoblast cells in rats. Separated and cultured primary skeletal myoblast cells from rats were treated by insulin. By means of the incorporation of (3)H-TdR, BrdU assay and MTT assay, the proliferation of skeletal myoblast cells was detected. Western blot was used to check the phosphorylation of Akt and ERK of myoblast cells. The results showed that insulin significantly promoted the incorporation of (3)H-TdR into cultured skeletal myoblast cells in a dose-dependent manner. MTT assay and BrdU assay also showed insulin promoted the proliferation of skeletal myoblast cells. The promotion of skeletal myoblast cells proliferation by insulin was inhibited by PI3K inhibitor wortmannin or MEK inhibitor U0126, and the same phenomenon was shown in L6 and C2C12 cells. Also, insulin increased the phosphorylation of Akt and ERK in myoblast cells. These results suggest that insulin may promote proliferation of skeletal myoblast cells through PI3K/Akt and MEK/ERK pathways.

HPV infection and p53 inactivation in pterygium.

PURPOSE: Our recent report indicated that tumor suppressor gene (p53) mutations and protein aberrant expression were detected in pterygium. Inactivation of p53 by Human papillomavirus (HPV) 16/18 E6 plays a crucial role in cervical tumorigenesis. In this study, we further speculate that p53 inactivation may be linked with HPV infection in pterygium pathogenesis. To investigate the involvement of HPV 16/18 E6 in p53 inactivation in pterygium, the association between HPV 16 or HPV 18 infection, the HPV E6 oncoprotein, and p53 protein expression was analyzed in this study. METHODS: HPV 16/18 infection was detected by nested-polymerase chain reaction (nested-PCR), the p53 mutation was detected by direct sequencing, and the p53 and the HPV 16/18 E6 proteins were studied using immunohistochemistry on 129 pterygial specimens and 20 normal conjunctivas. RESULTS: The HPV 16/18 was detected in 24% of the pterygium tissues (31 of 129) but not in the normal conjunctiva, and the HPV16/18 E6 oncoprotein was detected in 48.3% of HPV 16/18 DNA-positive pterygium tissues (15 of 31). In addition, p53 protein negative expression in pterygium was correlated with HPV16/18 E6 oncoprotein expression but not with a p53 mutation. CONCLUSIONS: HPV 16/18 E6 contributes to HPV-mediated pterygium pathogenesis as it is partly involved in p53 inactivation and is expressed in HPV DNA-positive pterygium.

Hypermethylation of the p16 gene promoter in pterygia and its association with the expression of DNA methyltransferase 3b.

PURPOSE: A pterygium has long been considered as a degenerative condition. After p53 protein was found to be abnormally expressed in the epithelium, researchers suggested that a pterygium may be a tumor, but additional evidence is required to support this hypothesis. Aberrant methylation of the p16 gene (CDKN2A) promoter and resultant gene silencing play important roles in the pathogenesis of many types of human cancers. The purpose of this study was to investigate hypermethylation of the p16 promoter in pterygia and the relationship between this hypermethylation and the expression of p16 and DNA methyltransferase 3b (DNMT3b) proteins. METHODS: We studied the methylation status of p16 and the expression of p16 and DNMT3b proteins by performing methylation-specific polymerase chain reaction and immunohistochemistry, respectively, in specimens of 129 pterygia and 16 normal conjunctiva. The results were statistically analyzed. RESULTS: Hypermethylation of the p16 gene promoter was detected in 21 (16.3%) of 129 pterygial specimens. Among them, 46 (35.7%) were positive for p16 protein expression, and 83 (64.3%) were negative. Staining for p16 was limited to the nuclei of the epithelial layer. We observed a significant reverse correlation between hypermethylation of the p16 promoter and the expression of p16 protein (p=0.006). Thirty-eight (29.5%) pterygial specimens were positive for DNMT3b protein expression, and 91 (70.5%) were negative. DNMT3b staining was limited to the nuclei of the epithelial layer. A significant correlation was found between hypermethylation of the p16 promoter and the expression of DNMT3b protein (p<0.001). CONCLUSIONS: The p16 gene promoter was hypermethylated in pterygia, and this hypermethylation was strongly linked to expression of the positive expression of DNMT3b protein and to the suppression of p16 protein. These data provided molecular evidence that methylation occurs in pterygia and that it may play a role in the their development.