BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remai...BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remains partly unknown.METHODS The Mendelian randomization(MR)was used to test genetic,potentially causal relationships between instrumental variables and cardiometabolic traits.Genetic variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental variables.Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen,CARDIoGRAM and CARDIoGRAMplusC4D,CHARGE,and MEGASTROKE.This study was conducted using summary statistic data from large,previously described cohorts.Association between thyroid function and essential hypertension(EHTN),secondary hypertension(SHTN),hyperlipidemia(HPL),type 2 diabetes mellitus(T2DM),ischemic heart disease(IHD),myocardial infarction(MI),heart failure(HF),pulmonary heart disease(PHD),stroke,and non-rheumatic valve disease(NRVD)were examined.RESULTS Genetically predicted FT4 levels were associated with SHTN(odds ratio=0.48;95%CI=0.04−0.82,P=0.027),HPL(odds ratio=0.67;95%CI=0.18−0.88,P=0.023),T2DM(odds ratio=0.80;95%CI=0.42−0.86,P=0.005),IHD(odds ratio=0.85;95%CI=0.49−0.98,P=0.039),NRVD(odds ratio=0.75;95%CI=0.27−0.97,P=0.039).Additionally,genetically predicted TSH levels were associated with HF(odds ratio=0.82;95%CI=0.68−0.99,P=0.042),PHD(odds ratio=0.75;95%CI=0.32−0.82,P=0.006),stroke(odds ratio=0.95;95%CI=0.81−0.97,P=0.007).However,genetically predicted thyroid function traits were not associated with EHTN and MI.CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.展开更多
Risk prediction tools are crucial for population-based management of cardiovascular disease(CVD).However,most prediction models are currently used to assess long-term risk instead of the risk of short-term CVD onset.W...Risk prediction tools are crucial for population-based management of cardiovascular disease(CVD).However,most prediction models are currently used to assess long-term risk instead of the risk of short-term CVD onset.We developed a Dynamic Risk-based Early wAming Monitoring(DREAM)system using large-scale,real-time electronic health record data from 2010 to 2020 from the CHinese Electronic health Records Research in Yinzhou study.The dynamic risk scores were derived from a 1:5 matched nested case-control set comprising 70,470 individuals(11,745 CVD events)and then validated in a cohort of 81,205 individuals(5950 CVD events).The individuals were Chinese adults aged 40-79 years without a history of CVD at baseline.Eleven predictors related to vital signs,laboratory tests,and health service utilization were selected to establish the dynamic scores.The proposed scores were significantly associated with the subsequent CVD onset(adjusted odds ratio,1.21;95%confidence interval,1.20-1.23).The area under the receiver operating characteristic curves(AUCs)was 0.6010(0.5929-0.6092)and 0.6021(0.5937-0.6105)for the long-term 10-year CVD risk<10%and≥10%groups in the derivation set,respectively.In the long-term 10-year CVD risk>10%group in the validation set,the change in AUC in addition to the long-term risk was 0.0235(0.0155-0.0315).By increasing the risk threshold from 7 to 16 points,the proportion of true subsequent CVD cases among those given alerts increased from 40.61%to 85.31%.In terms of management efficiency,the number needed to manage per CVD case ranged from 2.46 to 1.17 using the risk scores.With the increasing popularity and integration of EHR systems with wearable technology,the DREAM scores can be incorporated into an early-warning system and applied in dynamic,real-time,EHR-based,automated management to support healthcare decision making for individuals,general practitioners,and policymakers.展开更多
Background:At present,a large number of chronic obstructive pulmonary disease(COPD)patients are undiagnosed in China.Thus,this study aimed to develop a simple prediction model as a screening tool to identify patients ...Background:At present,a large number of chronic obstructive pulmonary disease(COPD)patients are undiagnosed in China.Thus,this study aimed to develop a simple prediction model as a screening tool to identify patients at risk for COPD.Methods:The study was based on the data of 22,943 subjects aged 30 to 79 years and enrolled in the second resurvey of China Kadoorie Biobank during 2012 and 2013 in China.We stepwisely selected the predictors using logistic regression model.Then we tested the model validity through P-P graph,area under the receiver operating characteristic curve(AUROC),ten-fold cross validation and an external validation in a sample of 3492 individuals from the Enjoying Breathing Program in China.Results:The final prediction model involved 14 independent variables,including age,sex,location(urban/rural),region,educational background,smoking status,smoking amount(pack-years),years of exposure to air pollution by cooking fuel,family history of COPD,history of tuberculosis,body mass index,shortness of breath,sputum and wheeze.The model showed an area under curve(AUC)of 0.72(95%confidence interval[CI]:0.72-0.73)for detecting undiagnosed COPD patients,with the cutoff of predicted probability of COPD=0.22,presenting a sensitivity of 70.13%and a specificity of 62.25%.The AUROC value for screening undiagnosed patients with clinically significant COPD was 0.68(95%CI:0.66-0.69).Moreover,the ten-fold cross validation reported an AUC of 0.72(95%CI:0.71-0.73),and the external validation presented an AUC of 0.69(95%CI:0.68-0.71).Conclusion:This prediction model can serve as a first-stage screening tool for undiagnosed COPD patients in primary care settings.展开更多
Stearoyl-CoA desaturase 1(SCD1)converts saturated fatty acids to monounsaturated fatty acids.The expression of SCD1 is increased in many cancers,and the altered expression contributes to the proliferation,invasion,ste...Stearoyl-CoA desaturase 1(SCD1)converts saturated fatty acids to monounsaturated fatty acids.The expression of SCD1 is increased in many cancers,and the altered expression contributes to the proliferation,invasion,stemness and chemoresistance of cancer cells.Recently,more evidence has been reported to further support the important role of SCD1 in cancer,and the regulation mechanism of SCD1 has also been focused.Multiple factors are involved in the regulation of SCD1,including metabolism,diet,tumor microenvironment,transcription factors,non-coding RNAs,and epigenetics modification.Moreover,SCD1 is found to be involved in regulating ferroptosis resistance.Based on these findings,SCD1 has been considered as a potential target for cancer treatment.However,the resistance of SCD1 inhibition may occur in certain tumors due to tumor heterogeneity and metabolic plasticity.This review summarizes recent advances in the regulation and function of SCD1 in tumors and discusses the potential clinical application of targeting SCD1 for cancer treatment.展开更多
Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produce...Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions.Mechanistically,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors.Disruption of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.展开更多
Background:Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease(COPD),but this is unclear in the Chinese population.We examined the associatio...Background:Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease(COPD),but this is unclear in the Chinese population.We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide,population-based prospective cohort from China.Methods:Between 2004 and 2008,the China Kadoorie Biobank recruited>0.5 million adults aged 30 to 79 years from ten diverse regions across China.After excluding individuals diagnosed with major chronic diseases and prevalent COPD,the prospective analysis included 421,428 participants.Cox regression was used to calculate the hazard ratios(HRs)for the association between fresh fruit consumption and risk of COPD-related hospitalization and death,with adjustment for established and potential confounders.Results:During a mean follow-up of 10.9 years,11,292 COPD hospitalization events and deaths were documented,with an overall incidence rate of 2.47/1000 person-years.Participants who consumed fresh fruit daily had a 22%lower risk of COPD-related hospitalization and death compared with non-consumers(HR=0.78,95%confidence interval[CI]:0.71-0.87).The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index(BMI)(18.5 kg/m^(2)≤BMI<24.0 kg/m^(2));the corresponding HRs for daily fresh fruit consumption were 0.78(95%CI:0.68-0.89)and 0.69(95%CI:0.59-0.79)compared with their counterparts,respectively.Conclusions:High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults.Increasing fruit consumption,together with cigarette cessation and weight control,should be considered in the prevention and management of COPD.展开更多
Background:Thyroid dysfunction is associated with cardiovascular diseases.However,the role of thyroid function in lipid metabolism remains partly unknown.The present study aimed to investigate the causal association b...Background:Thyroid dysfunction is associated with cardiovascular diseases.However,the role of thyroid function in lipid metabolism remains partly unknown.The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization(MR).Methods:The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial.A two-sample MR was performed to assess the causal association,using summary statistics from the Atrial Fibrillation Genetics Consortium(n=537,409)and the Global Lipids Genetics Consortium(n=188,577).The clinical measures of thyroid function include thyrotropin(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)levels,FT3:FT4 ratio and concentration of thyroid peroxidase antibodies(TPOAb).The serum lipid metabolism traits include total cholesterol(TC)and triglycerides,high-density lipoprotein,and low-density lipoprotein(LDL)levels.The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.Results:The results demonstrated that increased TSH levels were significantly associated with higher TC(β=0.052,P=0.002)and LDL(β=0.041,P=0.018)levels.In addition,the FT3:FT4 ratio was significantly associated with TC(β=0.240,P=0.033)and LDL(β=0.025,P=0.027)levels.However,no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.Conclusion:Taken together,the results of the present study suggest an association between thyroid function and serum lipid metabolism,highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.展开更多
Background:Most lung cancer risk prediction models were developed in European and North-American cohorts of smokers aged≥55 years,while less is known about risk profiles in Asia,especially for never smokers or indivi...Background:Most lung cancer risk prediction models were developed in European and North-American cohorts of smokers aged≥55 years,while less is known about risk profiles in Asia,especially for never smokers or individuals aged<50 years.Hence,we aimed to develop and validate a lung cancer risk estimate tool for ever and never smokers across a wide age range.Methods:Based on the China Kadoorie Biobank cohort,we first systematically selected the predictors and explored the nonlinear association of predictors with lung cancer risk using restricted cubic splines.Then,we separately developed risk prediction models to construct a lung cancer risk score(LCRS)in 159,715 ever smokers and 336,526 never smokers.The LCRS was further validated in an independent cohort over a median follow-up of 13.6 years,consisting of 14,153 never smokers and 5,890 ever smokers.Results:A total of 13 and 9 routinely available predictors were identified for ever and never smokers,respectively.Of these predictors,cigarettes per day and quit years showed nonlinear associations with lung cancer risk(Pnon-linear<0.001).The curve of lung cancer incidence increased rapidly above 20 cigarettes per day and then was relatively flat until approximately 30 cigarettes per day.We also observed that lung cancer risk declined sharplywithin the first 5 years of quitting,and then continued to decrease but at a slower rate in the subsequent years.The 6-year area under the receiver operating curve for the ever and never smokers’models were respectively 0.778 and 0.733 in the derivation cohort,and 0.774 and 0.759 in the validation cohort.In the validation cohort,the 10-year cumulative incidence of lung cancerwas 0.39%and 2.57%for ever smokers with low(<166.2)and intermediate-high LCRS(≥166.2),respectively.Never smokers with a high LCRS(≥21.2)had a higher 10-year cumulative incidence rate than those with a low LCRS(<21.2;1.05%vs.0.22%).An online risk evaluation tool(LCKEY;http://ccra.njmu.edu.cn/lckey/web)was developed to facilitate the use of LCRS.Conclusions:The LCRS can be an effective risk assessment tool designed for ever and never smokers aged 30 to 80 years.展开更多
文摘BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remains partly unknown.METHODS The Mendelian randomization(MR)was used to test genetic,potentially causal relationships between instrumental variables and cardiometabolic traits.Genetic variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental variables.Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen,CARDIoGRAM and CARDIoGRAMplusC4D,CHARGE,and MEGASTROKE.This study was conducted using summary statistic data from large,previously described cohorts.Association between thyroid function and essential hypertension(EHTN),secondary hypertension(SHTN),hyperlipidemia(HPL),type 2 diabetes mellitus(T2DM),ischemic heart disease(IHD),myocardial infarction(MI),heart failure(HF),pulmonary heart disease(PHD),stroke,and non-rheumatic valve disease(NRVD)were examined.RESULTS Genetically predicted FT4 levels were associated with SHTN(odds ratio=0.48;95%CI=0.04−0.82,P=0.027),HPL(odds ratio=0.67;95%CI=0.18−0.88,P=0.023),T2DM(odds ratio=0.80;95%CI=0.42−0.86,P=0.005),IHD(odds ratio=0.85;95%CI=0.49−0.98,P=0.039),NRVD(odds ratio=0.75;95%CI=0.27−0.97,P=0.039).Additionally,genetically predicted TSH levels were associated with HF(odds ratio=0.82;95%CI=0.68−0.99,P=0.042),PHD(odds ratio=0.75;95%CI=0.32−0.82,P=0.006),stroke(odds ratio=0.95;95%CI=0.81−0.97,P=0.007).However,genetically predicted thyroid function traits were not associated with EHTN and MI.CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.
基金supported by the National Natural Science Foundation of China[Grant No.91846112,81973132,81961128006]the Chinese Ministry of Science and Technology[Grant No.2020YFC2003503].
文摘Risk prediction tools are crucial for population-based management of cardiovascular disease(CVD).However,most prediction models are currently used to assess long-term risk instead of the risk of short-term CVD onset.We developed a Dynamic Risk-based Early wAming Monitoring(DREAM)system using large-scale,real-time electronic health record data from 2010 to 2020 from the CHinese Electronic health Records Research in Yinzhou study.The dynamic risk scores were derived from a 1:5 matched nested case-control set comprising 70,470 individuals(11,745 CVD events)and then validated in a cohort of 81,205 individuals(5950 CVD events).The individuals were Chinese adults aged 40-79 years without a history of CVD at baseline.Eleven predictors related to vital signs,laboratory tests,and health service utilization were selected to establish the dynamic scores.The proposed scores were significantly associated with the subsequent CVD onset(adjusted odds ratio,1.21;95%confidence interval,1.20-1.23).The area under the receiver operating characteristic curves(AUCs)was 0.6010(0.5929-0.6092)and 0.6021(0.5937-0.6105)for the long-term 10-year CVD risk<10%and≥10%groups in the derivation set,respectively.In the long-term 10-year CVD risk>10%group in the validation set,the change in AUC in addition to the long-term risk was 0.0235(0.0155-0.0315).By increasing the risk threshold from 7 to 16 points,the proportion of true subsequent CVD cases among those given alerts increased from 40.61%to 85.31%.In terms of management efficiency,the number needed to manage per CVD case ranged from 2.46 to 1.17 using the risk scores.With the increasing popularity and integration of EHR systems with wearable technology,the DREAM scores can be incorporated into an early-warning system and applied in dynamic,real-time,EHR-based,automated management to support healthcare decision making for individuals,general practitioners,and policymakers.
基金supported by the National Key Research&Development Program of China(Nos.2016YFC1303904 and 2016YFC0900500)National Natural Science Foundation of China(Nos.81941018,91846303,and 91843302)
文摘Background:At present,a large number of chronic obstructive pulmonary disease(COPD)patients are undiagnosed in China.Thus,this study aimed to develop a simple prediction model as a screening tool to identify patients at risk for COPD.Methods:The study was based on the data of 22,943 subjects aged 30 to 79 years and enrolled in the second resurvey of China Kadoorie Biobank during 2012 and 2013 in China.We stepwisely selected the predictors using logistic regression model.Then we tested the model validity through P-P graph,area under the receiver operating characteristic curve(AUROC),ten-fold cross validation and an external validation in a sample of 3492 individuals from the Enjoying Breathing Program in China.Results:The final prediction model involved 14 independent variables,including age,sex,location(urban/rural),region,educational background,smoking status,smoking amount(pack-years),years of exposure to air pollution by cooking fuel,family history of COPD,history of tuberculosis,body mass index,shortness of breath,sputum and wheeze.The model showed an area under curve(AUC)of 0.72(95%confidence interval[CI]:0.72-0.73)for detecting undiagnosed COPD patients,with the cutoff of predicted probability of COPD=0.22,presenting a sensitivity of 70.13%and a specificity of 62.25%.The AUROC value for screening undiagnosed patients with clinically significant COPD was 0.68(95%CI:0.66-0.69).Moreover,the ten-fold cross validation reported an AUC of 0.72(95%CI:0.71-0.73),and the external validation presented an AUC of 0.69(95%CI:0.68-0.71).Conclusion:This prediction model can serve as a first-stage screening tool for undiagnosed COPD patients in primary care settings.
基金supported by the National Natural Science Foundation of China (81672091,91749107,81972966,82272745,31925021,82203102)the National Key Research and Development Program of China (2022YFA1104001)。
文摘Stearoyl-CoA desaturase 1(SCD1)converts saturated fatty acids to monounsaturated fatty acids.The expression of SCD1 is increased in many cancers,and the altered expression contributes to the proliferation,invasion,stemness and chemoresistance of cancer cells.Recently,more evidence has been reported to further support the important role of SCD1 in cancer,and the regulation mechanism of SCD1 has also been focused.Multiple factors are involved in the regulation of SCD1,including metabolism,diet,tumor microenvironment,transcription factors,non-coding RNAs,and epigenetics modification.Moreover,SCD1 is found to be involved in regulating ferroptosis resistance.Based on these findings,SCD1 has been considered as a potential target for cancer treatment.However,the resistance of SCD1 inhibition may occur in certain tumors due to tumor heterogeneity and metabolic plasticity.This review summarizes recent advances in the regulation and function of SCD1 in tumors and discusses the potential clinical application of targeting SCD1 for cancer treatment.
基金supported by the National Natural Science Foundation of China(No.82130022,31925021)the National Key Research and Development Program of China(No.2018YFA0800700 and 2022YFC3401500).
文摘Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions.Mechanistically,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors.Disruption of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.
基金supported by grants from the National Key Research&Development Program of China(Nos.2016YFC0900500,2016YFC0900501,2016YFC0900504,and 2016YFC1303904)National Natural Science Foundation of China(Nos.81973125,81941018,91846303,and 91843302)
文摘Background:Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease(COPD),but this is unclear in the Chinese population.We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide,population-based prospective cohort from China.Methods:Between 2004 and 2008,the China Kadoorie Biobank recruited>0.5 million adults aged 30 to 79 years from ten diverse regions across China.After excluding individuals diagnosed with major chronic diseases and prevalent COPD,the prospective analysis included 421,428 participants.Cox regression was used to calculate the hazard ratios(HRs)for the association between fresh fruit consumption and risk of COPD-related hospitalization and death,with adjustment for established and potential confounders.Results:During a mean follow-up of 10.9 years,11,292 COPD hospitalization events and deaths were documented,with an overall incidence rate of 2.47/1000 person-years.Participants who consumed fresh fruit daily had a 22%lower risk of COPD-related hospitalization and death compared with non-consumers(HR=0.78,95%confidence interval[CI]:0.71-0.87).The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index(BMI)(18.5 kg/m^(2)≤BMI<24.0 kg/m^(2));the corresponding HRs for daily fresh fruit consumption were 0.78(95%CI:0.68-0.89)and 0.69(95%CI:0.59-0.79)compared with their counterparts,respectively.Conclusions:High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults.Increasing fruit consumption,together with cigarette cessation and weight control,should be considered in the prevention and management of COPD.
基金supported by the National Natural Science Foundation of China(No.81825003,91957123)the Peking University Start-up Grant(BMU2018YJ002)+1 种基金High-performance Computing Platform of Peking University and Beijing Technology and Business University Grant(No.88442Y0033)Thyroid Hormone Replacement for Subclinical Hypothyroidism and Dyslipidemia in Patients with Atherosclerotic Cardiovascular Diseases(NCT03606824)。
文摘Background:Thyroid dysfunction is associated with cardiovascular diseases.However,the role of thyroid function in lipid metabolism remains partly unknown.The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization(MR).Methods:The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial.A two-sample MR was performed to assess the causal association,using summary statistics from the Atrial Fibrillation Genetics Consortium(n=537,409)and the Global Lipids Genetics Consortium(n=188,577).The clinical measures of thyroid function include thyrotropin(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)levels,FT3:FT4 ratio and concentration of thyroid peroxidase antibodies(TPOAb).The serum lipid metabolism traits include total cholesterol(TC)and triglycerides,high-density lipoprotein,and low-density lipoprotein(LDL)levels.The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.Results:The results demonstrated that increased TSH levels were significantly associated with higher TC(β=0.052,P=0.002)and LDL(β=0.041,P=0.018)levels.In addition,the FT3:FT4 ratio was significantly associated with TC(β=0.240,P=0.033)and LDL(β=0.025,P=0.027)levels.However,no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.Conclusion:Taken together,the results of the present study suggest an association between thyroid function and serum lipid metabolism,highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.
基金National Natural Science Foundation of China,Grant/Award Numbers:81820108028,81922061,81973123,82273714,82192901,82192904,82192900Excellent Youth Foundation of Jiangsu Province,Grant/Award Number:BK20220100+3 种基金Research Unit of Prospective Cohort of Cardiovascular Diseases and CancerChinese Academy of Medical Sciences,Grant/Award Number:2019RU038Science and Technology Service Network Initiative of Chinese Academy of Sciences,Grant/Award Number:No.KFJ-STS-QYZD-2021-08-001the National Key Research and Development Program of China,Grant/Award Number:2016YFC0900500。
文摘Background:Most lung cancer risk prediction models were developed in European and North-American cohorts of smokers aged≥55 years,while less is known about risk profiles in Asia,especially for never smokers or individuals aged<50 years.Hence,we aimed to develop and validate a lung cancer risk estimate tool for ever and never smokers across a wide age range.Methods:Based on the China Kadoorie Biobank cohort,we first systematically selected the predictors and explored the nonlinear association of predictors with lung cancer risk using restricted cubic splines.Then,we separately developed risk prediction models to construct a lung cancer risk score(LCRS)in 159,715 ever smokers and 336,526 never smokers.The LCRS was further validated in an independent cohort over a median follow-up of 13.6 years,consisting of 14,153 never smokers and 5,890 ever smokers.Results:A total of 13 and 9 routinely available predictors were identified for ever and never smokers,respectively.Of these predictors,cigarettes per day and quit years showed nonlinear associations with lung cancer risk(Pnon-linear<0.001).The curve of lung cancer incidence increased rapidly above 20 cigarettes per day and then was relatively flat until approximately 30 cigarettes per day.We also observed that lung cancer risk declined sharplywithin the first 5 years of quitting,and then continued to decrease but at a slower rate in the subsequent years.The 6-year area under the receiver operating curve for the ever and never smokers’models were respectively 0.778 and 0.733 in the derivation cohort,and 0.774 and 0.759 in the validation cohort.In the validation cohort,the 10-year cumulative incidence of lung cancerwas 0.39%and 2.57%for ever smokers with low(<166.2)and intermediate-high LCRS(≥166.2),respectively.Never smokers with a high LCRS(≥21.2)had a higher 10-year cumulative incidence rate than those with a low LCRS(<21.2;1.05%vs.0.22%).An online risk evaluation tool(LCKEY;http://ccra.njmu.edu.cn/lckey/web)was developed to facilitate the use of LCRS.Conclusions:The LCRS can be an effective risk assessment tool designed for ever and never smokers aged 30 to 80 years.
基金supported by the National Natural Science Foundation of China (81974490)the 2019 Irma and Paul MilsteinProgram for Senior Health Research Project Award。
