Deciphering the folate puzzle: Unraveling the impact of genetic variations and metabolites on cancer risk.

The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60-0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77-0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02-3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.

The combined effect of MTHFR C677T and A1298C polymorphisms on the risk of digestive system cancer among a hypertensive population.

BACKGROUND AND PURPOSE: The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case-control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS). METHODS: We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer. RESULTS: The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups. CONCLUSION: These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer.

The Mediating Effect of the Choline-to-Betaine Ratio on the Association Between PEMT rs7946 and Digestive System Cancer: A Nested Case-Control Study in a Chinese Population.

Background: The enzyme phosphatidylethanolamine N-methyltransferase (PEMT) is responsible for synthesizing phosphatidylcholine by methylating phosphatidylethanolamine. We hypothesized that a polymorphism of the PEMT gene, rs7946, is involved in carcinogenesis. Objectives: We aimed to investigate the relationship between PEMT rs7946 and digestive system cancer and examine possible effect modifiers and mediators. Methods: We conducted a nested, case-control study within the China H-type Hypertension Registry Study, including 751 cases and 1:1 matched controls. To assess the association of PEMT rs7946 and digestive system cancer, we estimated odds ratios with 95% confidence intervals (CIs) using conditional logistic regression. We used the bootstrap test to examine the potential mediating effects of related metabolites. Results: Our results revealed that wild-type homozygous CC genotype carriers of PEMT rs7946 had a significantly increased risk [odds ratio (OR): 1.31; 95% CI: 1.04, 1.66; P = 0.023] compared with the TT/CT combined genotypes. The effect was found to be more pronounced in individuals with a lower choline-to-betaine ratio (<0.412, P-interaction = 0.021). Furthermore, the mediation analysis indicated that the choline-to-betaine ratio played a significant role in mediating 13.55% of the association between PEMT rs7946 and digestive system cancer (P = 0.018). Conclusions: Our study suggested that PEMT rs7946 may affect risk of digestive system cancer through direct and indirect pathways, and the choline-to-betaine ratio may partially mediate the indirect effect.This trial was registered at Chinese Clinical Trial Registry as ChiCTR1800017274.

The association of serum choline concentrations with the risk of cancers: a community-based nested case-control study.

Few studies have been designed to investigate the effect of serum choline on the risk of incident cancer. This study aims to explore the association between serum choline and the risk of new-onset cancer. We conducted a case-control study, including 199 patients with incident cancer and 199 matched controls during a median of 3.9 years of follow-up, nested within the China Stroke Primary Prevention Trial. Cubic spline regression (RCS) and conditional logistic regression analysis was used to assess the association of serum choline and incident cancer risk. We observed a positive dose-response association between serum choline levels and the risk of overall (p for overall = 0.046) and digestive system cancer (p for overall = 0.039). Compared with patients with the lowest choline levels (Q1 group), patients in the highest levels of choline (Q4) had a 3.69-fold and 6.01-fold increased risk of overall (OR = 3.69, 95% CI 1.17-11.63) and digestive system cancer (OR = 6.01, 95% CI 1.14-31.67). Elevated choline levels (per SD, 11.49 µg/mL) were associated with a higher risk of overall cancer among participants who were older, male, and smokers in the subgroup analyses. We found a positive association between elevated levels of serum choline with increased risk of incident cancer. Our findings have critical clinical implications for cancer prevention and diagnosis.Trial registration CSPPT, NCT00794885. Registered: November 20, 2008. https://www.clinicaltrials.gov/ct2/show/study/NCT00794885 https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.

Poor sleep quality association with higher lung cancer risk: a nested case-control study.

Background: Little is known about the relationship between sleep quality and lung cancer incidence. Thus, this study was conducted to investigate the potential connection between sleep quality and lung cancer incidence. Methods: We performed and selected a nested case-control study that included 150 lung cancer cases and 150 matched controls based on the Lianyungang cohort. Univariate and multivariate logistic regression was utilized to investigate the connection between potential risk factors and lung cancer incidence risk. Results: In this study, the average age of participants was 66.5 ± 9.1 years, with 58.7% being male, and 52.7% reportedly experiencing sleep quality problems. The results of multivariate logistic regression showed that poor sleep quality was connected to an increased lung cancer incidence risk (P = 0.033, odds ratio = 1.83, 95% confidence interval = [1.05-3.19]) compared with those with good sleep quality. The stratified analyses showed a significantly positive connection between poor sleep quality (vs. good sleep quality) and cancer risk in smokers (vs. non-smoker, P for interaction = 0.085). The combined effect analysis indicated that smokers with poor sleep quality suffered from a 2.79-fold increase in cancer incidence rates when compared with non-smokers with good sleep quality. Conclusions: Poor sleep quality was positively connected to an increased lung cancer incidence risk. In addition, among those individuals with poor sleep quality, smoking increased the lung cancer incidence risk.

The association of serum betaine concentrations with the risk of new-onset cancers: results from two independent nested case-control studies.

Evidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the "H-type Hypertension Prevention and Control Public Service Project" (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99-1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine < 5.01 mmol/L, OR = 0.82, 95%CI = 0.59-1.14, p = 0.228; betaine ≥ 5.01 mmol/L, OR = 1.08, 95%CI = 1.01-1.17, p = 0.036). In the validation cohort, a significant association between serum betaine as a continuous variable and total cancer (OR = 1.48, 95%CI = 1.06-2.05, P = 0.020) was also found. High serum betaine was associated with increased risk of total cancer and lung cancer, and a U-shaped association was found with the risk of digestive cancers, with a turning point at about 5.01 mmol/L.

Association of plasma iron with the risk of incident cancer in Chinese adults with hypertension: a nested case-control study.

Background: Iron is an essential element for organismal health but excessive iron is potentially toxic. However, few observational studies link plasma iron (PI) concentrations and cancer risk, and the results are inconsistent. Objective: This study aimed to explore the associations of PI concentrations with cancer risk in Chinese adults with hypertension. Methods: We conducted a nested, case-control study, including 223 pairs of incident cancer cases and matched controls from the China Stroke Primary Prevention Trial. The median time between blood sample collection and subsequent cancer event occurrence was 2.13 years. The odds ratio (OR) and 95% confidence interval (CI) for the risk of cancer by PI were estimated from multivariable conditional logistic regression models. Results: There was a nonlinear association between PI concentrations and total cancer risk. When compared with participants in tertile 2 of PI, the ORs of total cancer were 2.17 (95%CI: 1.25-3.85) and 1.29 (95%CI: 0.77-2.19) in participants in PI tertiles 3 and 1, respectively. Furthermore, higher PI was associated with increased digestive system cancer risk (OR=3.25, 95%CI:1.29-8.90), while lower PI was associated with increased risk of non-digestive system cancer (OR=3.32, 95%CI: 1.39-8.71). In a sensitivity analysis, the increases in total cancer risk or digestive system cancer risk were still observed with higher PI after excluding cancer cases occurring within the first year. Conclusion: Our results showed an increased risk of cancer related to higher PI or lower PI in Chinese adults with hypertension. Higher iron levels were linked to an increased risk of digestive system cancers, whereas lower iron levels were linked to an increased risk of non-digestive system cancers.

The association of serum serine levels with the risk of incident cancer: results from a nested case-control study.

Background: Cancer is associated with the dysregulation of serum serine levels, and tumor growth is supported by increased serine biosynthesis. This study aims to explore the association of serum serine levels with incident cancer risk in Chinese hypertensive adults. Materials and methods: 1391 patients with incident cancer and 1391 matched controls in terms of age, sex, and residence with cases in a 1 : 1 ratio were included in this nested case-control study. The serum serine concentrations were determined by liquid chromatography with tandem quadrupole mass spectrometry (LC-MS/MS) at the baseline. The associations of serum serine levels with the risk of overall, digestive system, non-digestive system, and lung cancers (the most common type) were assessed by conditional logistic regression. Results: When serum serine concentration was assessed as quartiles, a significantly higher risk of total cancer (OR = 1.32; 95% CI: 1.01-1.71; P = 0.038) was found in participants in the highest quartile (≥17.68 µg mL-1) compared with participants in the lowest quartile (<13.27 µg mL-1). Similar results were also observed for non-digestive system and lung cancers, but not for digestive system cancers. Significant associations of serum with overall cancer risk were found among all age subgroups, men, non-smokers, non-drinkers, and individuals with lower folic acid levels. Conclusion: High serum serine concentrations were associated with an increased risk of overall, non-digestive system, and lung cancers among Chinese hypertensive adult patients.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

Positive correlation between hypertensive retinopathy and albuminuria in hypertensive adults.

PURPOSE: We investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults. METHODS: This was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria. RESULTS: HR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, ß = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, ß = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, ß = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014). CONCLUSION: HR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

Serum total folate, 5-methyltetrahydrofolate and vitamin B12 concentrations on incident risk of lung cancer.

Tobacco smoking is a major known risk factor for lung cancer. While micronutrients, especially those involved in maintaining DNA integrity and regulating gene expression, may be protective, research on this association is limited. This report aimed to investigate associations of total folate, 5-methyltetrahydrofolate (5-mTHF) and vitamin B12 with incident risk of lung cancer, and whether the associations vary by smoking status. A nested case-control study with 490 incident lung cancer cases and 490 controls matched by age (±1 year), sex, residence, and center, drawn from a community-based prospective study in China, was conducted from 2016 to 2019. 5-mTHF accounted for the majority of total folate. Only 4.4% had detectable unmetabolized folic acid. Lung cancer cases had lower levels of 5-mTHF compared to controls. There was an inverse, nonlinear association between 5-mTHF and lung cancer, which persisted after adjustment for covariables (P for trend = .001). Compared to the lowest 5-mTHF quartile, those in higher quartiles had lower risks of lung cancer: second quartile OR = 0.65; 95% CI: 0.45-0.93; third quartile OR = 0.50; 95% CI: 0.34-0.74; fourth quartile OR = 0.56; 95% CI: 0.38-0.83. This inverse association was more pronounced among ever smokers; consistently, the highest risk of lung cancer (OR = 3.21, 95% CI: 1.97-5.24) was observed among ever smokers with low 5-mTHF levels compared to participants who never smoked and had higher 5-mTHF levels. Vitamin B12 was not associated with lung cancer risk. In this sample of Chinese adults without confounding by unmetabolized folic acid, higher levels of 5-mTHF were associated with lower risk of incident lung cancer.

Association between serum arginine levels and cancer risk: A community-based nested case-control study.

Objective: The effect of arginine on tumors appears to be bidirectional. The association of serum arginine with the risk of incident cancer remains uncovered at present. We aimed to investigate the prospective relationship of baseline serum arginine concentrations with the risk of incident cancer in hypertensive participants. Materials and methods: A nested, case-control study with 1,389 incident cancer cases and 1,389 matched controls was conducted using data from the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analyses were performed to evaluate the association between serum arginine and the risk of the overall, digestive system, non-digestive system, and site-specific cancer. Results: Compared with matched controls, cancer patients had higher levels of arginine (21.41 µg/mL vs. 20.88 µg/mL, p < 0.05). When serum arginine concentrations were assessed as quartiles, compared with participants in the lowest arginine quartile, participants in the highest arginine quartile had a 32% (OR = 1.32, 95% CI: 1.03 to 1.71), and 68% (OR = 1.68, 95% CI: 1.09 to 2.59) increased risk of overall and digestive system cancer, respectively, in the adjusted models. In the site-specific analysis, each standard deviation (SD) increment of serum arginine was independently and positively associated with the risk of colorectal cancer (OR = 1.35, 95% CI: 1.01 to 1.82) in the adjusted analysis. Conclusion: We found that hypertensive individuals with higher serum arginine levels exhibited a higher risk of overall, digestive system, and colorectal cancer.

The Association of Serum L-Carnitine Concentrations with the Risk of Cancer in Chinese Adults with Hypertension.

BACKGROUND: The effect of serum L-carnitine (LC) concentrations on cancer risk remains unclear. This study aims to explore the association between serum LC and the risk of incident cancer. METHODS: This is a case-control study, including 574 patients with incident cancer and 574 controls matched in a 1:1 ratio by age, sex, and residence, nested within the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analysis was used to assess the association of serum LC and incident cancer risk. RESULTS: When LC was assessed as quartiles, compared with patients with low LC (Q1), patients in the highest quartile (Q4) had a 33% (OR = 0.67, 95% CI: 0.46 to 0.99), 52% (OR = 0.48, 95% CI: 0.23 to 0.99), and 39% (OR = 0.61, 95% CI: 0.38 to 0.99) decreased risk of overall, digestive system, and non-digestive system cancer in the adjusted models, respectively. In subgroup analyses, an inverse association of LC with cancer risk was observed in individuals who were overweight (obese), who never drink, who never smoke, and who were female. In the mediation analysis, serum trimethylamine-N-oxide (TMAO) concentrations did not mediate the reversed association of LC with cancer risk. CONCLUSIONS: This study showed that serum LC concentrations had a protective impact on overall, digestive system, and non-digestive system cancer risk.

Genetically predicted iron status was associated with the risk of prostate cancer.

Introduction: Observational studies have reported a relationship between iron status and the risk of prostate cancer. However, it remains uncertain whether the association is causal or due to confounding or reverse causality. To further clarify the underlying causal relationship, we conducted a Mendelian randomization (MR) analysis. Methods: We selected three genetic variants (rs1800562, rs1799945, and rs855791) closely correlated with four iron status biomarkers (serum iron, log-transformed ferritin, transferrin saturation, and transferrin) as instrumental variables. Summary statistics for prostate cancer were obtained from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium including 79,148 cases and 61,106 controls of European ancestry. The inverse-variance weighted (IVW) method was conducted primarily to estimate the association of genetically predicted iron status and the risk of prostate cancer, supplemented with simple-median, weighted-median and maximum-likelihood methods as sensitivity analysis. MR-Egger regression was used to detect directional pleiotropy. We also conducted a meta-analysis of observational studies to assess the associations between iron status and the risk of prostate cancer. Results: Genetically predicted increased iron status was associated with the decreased risk of prostate cancer, with odds ratio of 0.91 [95% confidence interval (CI): 0.84, 0.99; P = 0.035] for serum iron, 0.81 (95% CI: 0.65, 1.00; P = 0.046) for log- transformed ferritin, 0.94 (95% CI: 0.88, 0.99; P = 0.029) for transferrin saturation, and 1.15 (95% CI: 0.98, 1.35; P = 0.084) for transferrin (with higher transferrin levels representing lower systemic iron status), using the inverse-variance weighted method. Sensitivity analyses produced consistent associations, and MR-Egger regression indicated no potential pleiotropy. Our replication analysis based on FinnGen research project showed compatible results with our main analysis. Results from our meta-analysis similarly showed that serum ferritin [standardized mean difference (SMD): -1.25; 95% CI: -2.34, -0.16; P = 0.024] and transferrin saturation (SMD: -1.19; 95% CI: -2.34, -0.05; P = 0.042) were lower in patients with prostate cancer compared with that in controls. Discussion: Our study suggests a protective role of iron in the risk of prostate cancer, further investigations are required to clarify the underlying mechanisms.

A sensitive UPLC-MS/MS method for simultaneous quantification of one-carbon metabolites & co-factors in human plasma.

One-carbon metabolism is an important metabolic pathway involved in many diseases, such as congenital malformations, tumours, cardiovascular diseases, anaemia, depression, cognitive diseases and liver disease. However, the current methods have specific defects in detecting and qualifying the related compounds of one-carbon metabolism. In this study, a validated method was established to simultaneously quantify 22 one-carbon metabolites & co-factors in human plasma and applied to the study of correlation between one-carbon metabolism and colorectal cancer in human plasma samples, which were from 44 healthy subjects and 55 colorectal cancer patients. The method used ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS), and the analytes included betaine, L-carnitine, L-cystathionine, L-cysteine, dimethylglycine, DL-homocysteic acid, homocysteine, methionine, pyridoxal hydrochloride, pyridoxamine dihydrochloride, pyridoxine dihydrochloride, S-(5'-Adenosyl)-L-homocysteine, serine, choline chloride, folic acid, glycine, pyridoxal phosphate monohydrate, riboflavin, taurine, 5-methyltetrahydrofolate, S-(5'-adenosyl)-L-methionine disulfate salt, trimethylamine oxide. The developed method was successfully applied to the quantification of 22 one-carbon metabolites & co-factors in human plasma from colorectal cancer patients and healthy individuals. The plasma concentrations of dimethylglycine was significantly decreased in the patients compared with the healthy individuals, while L-cystathionine was increased.

Global burden of musculoskeletal disorders and attributable factors in 204 countries and territories: a secondary analysis of the Global Burden of Disease 2019 study.

OBJECTIVE: To evaluate the global burden of musculoskeletal (MSK) disorders, as well as the five common conditions, and their relevant risk factors from 1990 to 2019. DESIGN: Data from the Global Burden of Disease Study 2019 were used in this study. SETTING AND PARTICIPANTS: Individuals of all ages and genders from 204 countries and territories in 21 regions. MAIN OUTCOME MEASURES: The outcomes were the numbers and age-standardised rates (ASRs) of incident cases, deaths and disability-adjusted life-years (DALYs) of MSK disorders. The average annual percent changes (AAPCs) in the ASRs were calculated using joinpoint regression analysis to estimate the trends. RESULTS: There were 322.75 million incident cases, 117.54 thousand deaths and 150.08 million DALYs of MSK disorders in 2019. The age-standardised incidence rate and age-standardised DALY rate in 2019 (incidence: AAPC=-0.32, 95% CI -0.34 to -0.31; DALYs: AAPC=-0.05, 95% CI -0.06 to -0.04) were lower than those in 1990. However, the age-standardised death rate showed a stable trend (AAPC 0.05, 95% CI -0.05 to 0.15) from 1990 to 2019. The peak age of onset and DALYs of MSK disorders was 50-54 years in 2019. The burden of MSK disorders in females was much higher than that in males (1.29 times more incident cases, 2.24 times more deaths and 1.45 times more DALYs in females than in males). A significant negative correlation was observed between the AAPCs in the ASRs and the Sociodemographic Index (SDI) score. Occupational risk exhibited the highest contribution to MSK disorders, and tobacco use and high body mass index were also major risk factors. CONCLUSIONS: This study demonstrates that the burden of MSK disorders tends to be lower in high-SDI regions than in lower-SDI regions. Strengthening the effectiveness of preventive measures against occupational risks may reduce the burden of MSK disorders.

Positive Association Between Serum Alkaline Phosphatase and First Stroke in Hypertensive Adults.

The relation of alkaline phosphatase (ALP) with stroke risk remains uncertain. We aimed to examine the association between serum ALP and the risk of first stroke, and explore the possible effect modifiers in the association, among adults with hypertension. A total of 19,747 participants with baseline ALP measurements and without liver disease at baseline from the China Stroke Primary Prevention Trial (CSPPT) were included. The primary outcome was a first stroke. Over a median follow-up of 4.5 years, there was a positive association between serum ALP levels and the risk of first stroke (per SD increment, adjusted HR, 1.10; 95%CI: 1.01, 1.20). When serum ALP was evaluated as quartiles, a significantly higher risk of first stroke was observed in those in quartile 2-4 (ALP ≥79 IU/L; adjusted HR, 1.38; 95% CI: 1.11, 1.71), compared with participants in quartile 1 (ALP <79 IU/L). Similar results were found for first ischemic or hemorrhagic stroke. Similar findings were also found in those with a normal range of baseline ALP levels (20-140 IU/L) (per SD increment, adjusted HR, 1.15; 95%CI: 1.05, 1.27). None of the variables, including sex, age, body mass index, smoking, alcohol drinking, blood pressure, total cholesterol, fasting glucose levels at baseline, and blood pressure levels during the treatment period, significantly modified the association. In summary, our study suggests that higher serum ALP levels, even in normal range, were significantly related to higher risk of first stroke among Chinese hypertensive adults.

Egg consumption associated with all-cause mortality in rural China: a 14-year follow-up study.

BACKGROUND: Dietary recommendations regarding egg intake remain controversial topic for public health. We hypothesized that there was a positive association between egg consumption and all-cause mortality. METHODS: To test this hypothesis, we enrolled 9885 adults from a community-based cohort in Anhui Province, China during 2003-05. Egg consumption was assessed by food questionnaire. Stratified analyses were performed for age, sex, body mass index (BMI), blood pressure, smoking, drinking and laboratory tests. RESULTS: After an average follow-up of 14.1 years, 9444 participants were included for analysis. A total of 814 deaths were recorded. Participants' BMI and lipid profile had no significantly difference between three egg consumption groups. BMI was 21.6±2.7 of the whole population, especially BMI>24 was only 17.3%. A bivariate association of egg consumption >6/week with increased all-cause mortality was observed compared with ≤6/week (RR: 1.35, 95% CI: 1.05, 1.73, P = 0.018). A significant interaction was observed for BMI ≥ 21.2 kg/m2 vs. BMI<21.2 kg/m2 (P for interaction: 0.001). No other significant interactions were found. CONCLUSIONS: In this study, consuming >6 eggs/week increased risk of all-cause mortality, even among lean participants, especially who with BMI ≥ 21.2 kg/m2. Eggs are an easily accessible and constitute an affordable food source in underdeveloped regions. Consuming <6 eggs/week may be the most suitable intake mode.

Cigarette smoking and all-cause mortality in rural Chinese male adults: 15-year follow-up of the Anqing cohort study.

BACKGROUND: According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population. METHODS: Male participants over age 45 (n = 5367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10 and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates. RESULTS: There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23-2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33-2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43-2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83-5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than never smokers or drinkers. (P for interaction = 0.034). CONCLUSIONS: This study provides evidence that current smokers and former smokers have a higher mortality risk than nonsmokers and would benefit from cessation at a younger age.

Interaction of Serum Alkaline Phosphatase and Folic Acid Treatment on Chronic Kidney Disease Progression in Treated Hypertensive Adults.

The relation of alkaline phosphatase (ALP) with chronic kidney disease (CKD) is still uncertain. We aimed to examine the prospective association between serum ALP and CKD progression, and the modifying effect of serum ALP on folic acid in preventing CKD progression in treated hypertensive patients. This is a post-hoc analysis of 12,734 hypertensive adults with relevant measurements and without liver disease at baseline from the renal sub-study of the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid, or 10 mg enalapril alone. The primary outcome was CKD progression, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of <60 ml/min/1.73 m2 if baseline eGFR was ≥60 ml/min/1.73 m2; or a decrease in eGFR of ≥50% if baseline eGFR was <60 ml/min/1.73 m2; or end-stage renal disease. Over a median of 4.4 years, in the enalapril only group, participants with baseline serum ALP≥110IU/L (quartile 4) had a significantly higher risk of CKD progression (3.4% vs 2.3%; adjusted OR,1.61; 95%CI:1.11, 2.32), compared with those with ALP<110IU/L. For those with enalapril and folic acid treatment, compared with the enalapril only treatment, the risk of CKD progression was reduced from 3.4 to 2.1% (adjusted OR, 0.53; 95%CI:0.34, 0.83) among participants with baseline ALP≥110IU/L, whereas there was no significant effect among those with ALP<110IU/L. In hypertensive patients, higher serum ALP was associated with increased risk of CKD progression, and this risk was reduced by 47% with folic acid treatment.