Socioeconomic characteristics, cancer mortality, and universal health coverage: A global analysis.

BACKGROUND: Achieving universal health coverage (UHC) involves all individuals attaining accessible health interventions at an affordable cost. We examined current patterns and temporal trends of cancer mortality and UHC across sociodemographic index (SDI) settings, and quantified these association. METHODS: We used data from the Global Burden of Disease Study 2019 and Our World in Data. The UHC effective coverage index was obtained to assess the potential population health gains delivered by health systems. The estimated annual percentage change (EAPC) with a 95% confidence interval (CI) was calculated to quantify the trend of cancer age-standardized mortality rate (ASMR). A generalized linear model was applied to estimate the association between ASMR and UHC. FINDINGS: The high (EAPC = -0.9% [95% CI, -1.0%, -0.9%]) and high-middle (-0.9% [-1.0%, -0.8%]) SDI regions had the fastest decline in ASMR (per 100,000) for total cancers from 1990 to 2019. The overall UHC effective coverage index increased by 27.9% in the high-SDI quintile to 62.2% in the low-SDI quintile. A negative association was observed between ASMR for all-cancer (adjusted odds ratio [OR] = 0.87 [0.76, 0.99]), stomach (0.73 [0.56, 0.95]), breast (0.64 [0.52, 0.79]), cervical (0.42 [0.30, 0.60]), lip and oral cavity (0.55 [0.40, 0.75]), and nasopharynx (0.42 [0.26, 0.68]) cancers and high UHC level (the lowest as the reference). CONCLUSIONS: Our findings strengthen the evidence base for achieving UHC to improve cancer outcomes. FUNDING: This work is funded by the China National Natural Science Foundation and Chinese Academy of Medical Sciences Innovation Fund for Medical Science.

Combining fecal immunochemical testing and questionnaire-based risk assessment in selecting participants for colonoscopy screening in the Chinese National Colorectal Cancer Screening Programs: A population-based cohort study.

BACKGROUND: Screening reduces colorectal cancer (CRC) burden by allowing early resection of precancerous and cancerous lesions. An adequate selection of high-risk individuals and a high uptake rate for colonoscopy screening are critical to identifying people more likely to benefit from screening and allocating healthcare resources properly. We evaluated whether combining a questionnaire-based interview for risk factors with fecal immunochemical test (FIT) outcomes for high-risk assessment is more efficient and economical than a questionnaire-based interview-only strategy. METHODS AND FINDINGS: In this multicenter, population-based, prospective cohort study, we enrolled community residents aged 40 to 74 years in 29 provinces across China. From 2016 to 2020, a total of 1,526,824 eligible participants were consecutively enrolled in the Cancer Screening Program in Urban China (CanSPUC) cohort, and 940,605 were enrolled in the Whole Life Cycle of Cancer Screening Program (WHOLE) cohort, with follow-up to December 31, 2022. The mean ages were 56.89 and 58.61 years in CanSPUC and WHOLE, respectively. In the WHOLE cohort, high-risk individuals were identified by combining questionnaire-based interviews to collect data on risk factors (demographics, diet history, family history of CRC, etc.) with FIT outcomes (RF-FIT strategy), whereas in the CanSPUC cohort, high-risk individuals were identified using only interview-based data on risk factors (RF strategy). The primary outcomes were participation rate and yield (detection rate of advanced neoplasm, early-stage detection rate of CRCs [stage I/II], screening yield per 10,000 invitees), which were reported for the entire population and for different gender and age groups. The secondary outcome was the cost per case detected. In total, 71,967 (7.65%) and 281,985 (18.47%) individuals were identified as high-risk and were invited to undergo colonoscopy in the RF-FIT group and RF group, respectively. The colonoscopy participation rate in the RF-FIT group was 26.50% (19,071 of 71,967) and in the RF group was 19.54% (55,106 of 281,985; chi-squared test, p < 0.001). A total of 102 (0.53%) CRCs and 2,074 (10.88%) advanced adenomas were detected by the RF-FIT, versus 90 (0.16%) and 3,593 (6.52%) by the RF strategy (chi-squared test, both p < 0.001). The early-stage detection rate using the RF-FIT strategy was significantly higher than that by the RF strategy (67.05% versus 47.95%, Fisher's exact test, p = 0.016). The cost per CRC detected was $24,849 by the RF-FIT strategy versus $55,846 by the RF strategy. A limitation of the study was lack of balance between groups with regard to family history of CRC (3.5% versus 0.7%). CONCLUSIONS: Colonoscopy participation and screening yield were better with the RF-FIT strategy. The association with CRC incidence and mortality reduction should be evaluated after long-term follow-up.

Risk-Adapted Starting Age of Personalized Lung Cancer Screening: A Population-Based, Prospective Cohort Study in China.

BACKGROUND: The current one-size-fits-all screening strategy for lung cancer is not suitable for personalized screening. RESEARCH QUESTION: What is the risk-adapted starting age of lung cancer screening with comprehensive consideration of risk factors? STUDY DESIGN AND METHODS: The National Lung Cancer Screening program, a multicenter, population-based, prospective cohort study, was analyzed. Information on risk factor exposure was collected during the baseline risk assessment. A Cox proportional hazards model was used to estimate the association between risk factors and lung cancer incidence. Age-specific 10-year cumulative risk was calculated to determine the age at which individuals with various risk factors reached the equivalent risk level as individuals aged ≥ 50 years with active tobacco use and a ≥ 20 pack-year smoking history. RESULTS: Of the 1,031,911 participants enrolled in this study, 3,908 demonstrated lung cancer after a median follow-up of 3.8 years. We identified seven risk factors for lung cancer, including pack-years of smoking, secondhand smoke exposure, family history of lung cancer in first-degree relatives, history of respiratory diseases, occupational hazardous exposure, BMI, and diabetes. The 10-year cumulative risk of lung cancer for people aged ≥ 50 years with active tobacco use and a ≥ 20 pack-year smoking history was 1.37%, which was treated as the risk threshold for screening. Individuals who never smoked and those with active tobacco use and a < 30-pack-year history of smoking reached the equivalent risk level 1 to 14 years later compared with the starting age of 50 years. Men with active tobacco use, a ≥ 30-pack-year history of smoking, and concurrent respiratory diseases or diabetes should be screened 1 year earlier at the age of 49 years. INTERPRETATION: The personalized risk-adapted starting ages for lung cancer screening, based on the principle of equal management of equal risk, can served as an optimized screening strategy to identify high-risk individuals.

Association Between Socioeconomic Status and Adherence to Fecal Occult Blood Tests in Colorectal Cancer Screening Programs: Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Screening adherence is important in reducing colorectal cancer (CRC) incidence and mortality. Disparity in CRC screening adherence was observed in populations of different socioeconomic status (SES), but the direction and strength of the association remained unclear. OBJECTIVE: We aimed to systematically review all the observational studies that have analyzed the association between SES and adherence to organized CRC screening based on fecal occult blood tests. METHODS: We systematically reviewed the studies in PubMed, Embase, and Web of Science and reference lists of relevant reviews from the inception of the database up until June 7, 2023. Individual SES, neighborhood SES, and small-area SES were included, while any SES aggregated by geographic areas larger than neighbors were excluded. Studies assessing SES with any index or score combining indicators of income, education, deprivation, poverty, occupation, employment, marital status, cohabitation, and others were included. A random effect model meta-analysis was carried out for pooled odds ratios (ORs) and relative risks for adherence related to SES. RESULTS: Overall, 10 studies, with a total of 3,542,379 participants and an overall adherence rate of 64.9%, were included. Compared with low SES, high SES was associated with higher adherence (unadjusted OR 1.73, 95% CI 1.42-2.10; adjusted OR 1.53, 95% CI 1.28-1.82). In the subgroup of nonindividual-level SES, the adjusted association was significant (OR 1.57, 95% CI 1.26-1.95). However, the adjusted association was insignificant in the subgroup of individual-level SES (OR 1.46, 95% CI 0.98-2.17). As for subgroups of the year of print, not only was the unadjusted association significantly stronger in the subgroup of early studies (OR 1.97, 95% CI 1.59-2.44) than in the subgroup of late studies (OR 1.43, 95% CI 1.31-1.56), but also the adjusted one was significantly stronger in the early group (OR 1.86, 95% CI 1.43-2.42) than in the late group (OR 1.26, 95% CI 1.14-1.39), which was consistent and robust. Despite being statistically insignificant, the strength of the association seemed lower in studies that did not adjust for race and ethnicity (OR 1.31, 95% CI 1.21-1.43) than the overall estimate (OR 1.53, 95% CI 1.28-1.82). CONCLUSIONS: The higher-SES population had higher adherence to fecal occult blood test-based organized CRC screening. Neighborhood SES, or small-area SES, was more competent than individual SES to be used to assess the association between SES and adherence. The disparity in adherence between the high SES and the low SES narrowed along with the development of interventions and the improvement of organized programs. Race and ethnicity were probably important confounding factors for the association.

Geographic disparities in trends of thyroid cancer incidence and mortality from 1990 to 2019 and a projection to 2030 across income-classified countries and territories.

Background: The rising incidence of thyroid cancer (TC) has generated growing concern globally; yet there are no studies examining whether this incidence was followed by a rise in related mortality. We aimed to comprehensively quantify current trends and future projections of TC incidence and mortality, and to explore the association between the TC burden and socioeconomic inequality in different income strata. Methods: We obtained incidence and mortality data on TC and population from the 2019 Global Burden of Disease (GBD) study and the United Nations' World Population Prospects 2022. We applied an age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) and age, period, and cohort effects from 1990 to 2019, and also constructed a Bayesian APC model to predict the TC burden through 2030. Results: Over a third of global TC cases belonged to the high-income group. From 1990 to 2019, net drifts of TC incidence were >0 in all income groups, while a modest reduction (net drift <0) in mortality was observed in most income groups, except for the lower-middle-income group. Unfavourable age, period, and cohort effects were most notable in Vietnam, China, and Korea. The age-standardised incidence rate (ASIR) is predicted to increase whereas the age-standardized mortality rate (ASMR) is expected to decrease globally between 2020 and 2030, with geographic heterogeneity being detected across income groups. We observed a positive correlation between ASIR and universal health coverage index and health worker density, but a negative one between ASMR and the two indicators, primarily in upper-middle-income and high-income countries. Conclusions: Opposite patterns in incidence and mortality of TC raise concerns about overdiagnosis, particularly in upper-middle-income and high-income countries. Discrepancies in the distribution of health service accessibility, including diagnostic techniques and therapeutic care, should be addressed by narrowing health inequalities in the TC burden across countries.

A strategy to reduce the false-positive rate after low-dose computed tomography in lung cancer screening: A multicenter prospective cohort study.

BACKGROUND: The ability of lung cancer screening to manage pulmonary nodules was limited because of the high false-positive rate in the current mainstream screening method, low-dose computed tomography (LDCT). We aimed to reduce overdiagnosis in Chinese population. METHODS: Lung cancer risk prediction models were constructed using data from a population-based cohort in China. Independent clinical data from two programs performed in Beijing and Shandong, respectively, were used as the external validation set. Multivariable logistic regression models were used to estimate the probability of lung cancer incidence in the whole population and in smokers and nonsmokers. RESULTS: In our cohort, 1,016,740 participants were enrolled between 2013 and 2018. Of 79,581 who received LDCT screening, 5165 participants with suspected pulmonary nodules were allocated into the training set, of which, 149 lung cancer cases were diagnosed. In the validation set, 1815 patients were included, and 800 developed lung cancer. The ages of patients and radiologic factors of nodules (calcification, density, mean diameter, edge, and pleural involvement) were included in our model. The area under the curve (AUC) values of the model were 0.868 (95% CI: 0.839-0.894) in the training set and 0.751 (95% CI: 0.727-0.774) in the validation set. The sensitivity and specificity were 70.5% and 70.9%, respectively, which could reduce the 68.8% false-positive rate in simulated LDCT screening. There was no substantial difference between smokers' and nonsmokers' prediction models. CONCLUSION: Our models could facilitate the diagnosis of suspected pulmonary nodules, effectively reducing the false-positive rate of LDCT for lung cancer screening.

Modifiable risk-attributable and age-related burden of lung cancer in China, 1990-2019.

BACKGROUND: There were limited studies on the quantification of the modifiable and nonmodifiable lung cancer burden over time in China. Furthermore, the potential effect of risk factor reduction for lung cancer on gains in life expectancy (LE) remains unknown. METHODS: This study explored temporal trends in lung cancer deaths and disability-adjusted life years (DALY) attributable to modifiable risk factors from 1990 to 2019, based on the 2019 Global Burden of Disease Study. The abridged period life table method was used to quantify the effect of risk factors on LE. The authors used the decomposition approach to estimate contributions of aging metrics to change in the lung cancer burden. RESULTS: Nationally, the majority of lung cancer deaths and DALYs were attributable to behavioral and environmental risk clusters. Potential gains in life expectancy (PGLE) at birth would be 0.78 years for males and 0.35 years for females if the exposure to risk factors was mitigated to the theoretical minimum level. Tobacco use had the most robust impact on LE for both sexes (PGLE: 0.71 years for males and 0.19 years for females). From 1990 to 2019, risk-attributable age-standardized death and DALY rates of lung cancer showed an increasing trend in both sexes; adult population growth imposed 245.9 thousand deaths and 6.2 million DALYs for lung cancer. CONCLUSIONS: The modifiable risk-attributable lung cancer burden remains high in China. Effective tobacco control is the critical step toward addressing the lung cancer burden. Adult population growth was the foremost driver of transition in the age-related lung cancer burden. PLAIN LANGUAGE SUMMARY: We estimate the lung cancer burden attributable to modifiable and nonmodifiable contributors and the effect of risk factor reduction for lung cancer on the life expectancy in China. The findings suggest that the majority of lung cancer deaths and disability-adjusted life years were attributable to behavioral risk clusters, and the risk-attributable lung cancer burden increased nationally from 1990 to 2019. The average gains in life expectancy would be 0.78 years for males and 0.35 years for females if the exposure to risk factors for lung cancer was reduced to the theoretical minimum risk exposure level. Adult population growth was identified as the foremost driver of variation in the aging lung cancer burden.

Risk-Adapted Starting Age for Personalized Colorectal Cancer Screening: Validated Evidence From National Population-Based Studies.

BACKGROUND & AIMS: A one-size-fits-all approach to colorectal cancer (CRC) screening that does not account for CRC risk factors is not conducive to personalized screening. On the basis of the principle of equal management of equal risks, we aimed to tailor and validate risk-adapted starting ages of CRC screening for individuals with different CRC risk factors. METHODS: A multi-center community-based population cohort (N = 3,165,088) was used to evaluate the starting age of CRC screening with comprehensive consideration of risk factors. Age-specific 10-year cumulative risk curves were used to determine when individuals at greater risk for CRC reached the same risk level as the 50-year-old general population, which is currently the recommended starting age for CRC screening in China. RESULTS: During the study follow-up period (2013-2021), 4,840 incident CRCs were recorded. Family history of CRC, adverse lifestyle, and comorbidities demonstrated heterogeneous associations with CRC risk (hazard ratios, 1.05-1.55; P < .05). Men and women with CRC family history and at least 2 risk factors reached the standard benchmark risk (0.28%) for screening at the age of 40, 10 years earlier than their peers without risk factors in the general population. Proposed starting ages for CRC screening were validated in an independent community-based population cohort (N = 1,023,367). CONCLUSIONS: We determined a risk-adapted CRC screening starting age for individuals with various CRC risk factors. Earlier, personalized screening based on these findings could allow for scarce health resources to be dedicated to individuals who benefit most.

Risk-stratified Approach for Never- and Ever-Smokers in Lung Cancer Screening: A Prospective Cohort Study in China.

Rationale: Over 40% of lung cancer cases occurred in never-smokers in China. However, high-risk never-smokers were precluded from benefiting from lung cancer screening as most screening guidelines did not consider them. Objectives: We sought to develop and validate prediction models for 3-year lung cancer risks for never- and ever-smokers, named the China National Cancer Center Lung Cancer models (China NCC-LCm2021 models). Methods: 425,626 never-smokers and 128,952 ever-smokers from the National Lung Cancer Screening program were used as the training cohort and analyzed using multivariable Cox models. Models were validated in two independent prospective cohorts: one included 369,650 never-smokers and 107,678 ever-smokers (841 and 421 lung cancers), and the other included 286,327 never-smokers and 78,469 ever-smokers (503 and 127 lung cancers). Measurements and Main Results: The areas under the receiver operating characteristic curves in the two validation cohorts were 0.698 and 0.673 for never-smokers and 0.728 and 0.752 for ever-smokers. Our models had higher areas under the receiver operating characteristic curves than other existing models and were well calibrated in the validation cohort. The China NCC-LCm2021 ⩾0.47% threshold was suggested for never-smokers and ⩾0.51% for ever-smokers. Moreover, we provided a range of threshold options with corresponding expected screening outcomes, screening targets, and screening efficiency. Conclusion: The construction of the China NCC-LCm2021 models can accurately reflect individual risk of lung cancer, regardless of smoking status. Our models can significantly increase the feasibility of conducting centralized lung cancer screening programs because we provide justified thresholds to define the high-risk population of lung cancer and threshold options to adapt different configurations of medical resources.

Use of Breast Cancer Risk Factors to Identify Risk-Adapted Starting Age of Screening in China.

Importance: Although current guidelines highlight the need for earlier screening in women at increased risk of breast cancer in China, data on risk-adapted starting ages of screening are limited. Objective: To explore the risk-adapted starting age of breast cancer screening in China, with comprehensive consideration of breast cancer risk factors. Design, Setting, and Participants: A multicenter community-based cohort study was conducted under the framework of the Cancer Screening Program in Urban China. Data were collected from January 1, 2013, to December 31, 2018, for unscreened community-dwelling women aged 40 to 74 years without a history of cancer, kidney dysfunction, or severe heart, brain, or lung disease. Data analysis was performed from October 1, 2021, to August 16, 2022. Exposures: Baseline characteristics associated with breast cancer, including first-degree family history of breast cancer, benign breast disease, breastfeeding, age at menarche, and body mass index. Main Outcomes and Measures: Outcomes included breast cancer diagnosis and age at diagnosis. Risk-adapted starting age of screening was defined as the age at which women with different levels of breast cancer risk attained a 10-year cumulative risk level similar to women aged 50 years in the general population. Results: Of the 1 549 988 women enrolled in this study, 3895 had breast cancer (median follow-up, 4.47 [IQR, 3.16-6.35] years). Participants were divided into different risk groups according to breast cancer risk scores (driven by risk factors including first-degree family history of breast cancer, benign breast disease, breastfeeding, age at menarche, and body mass index). Using the 10-year cumulative risk of breast cancer at age 50 years in the general population as a benchmark (2.65% [95% CI, 2.50%-2.76%]), the optimal starting age of screening for women with high, medium, or low risk of breast cancer was identified as 43, 48, or after 55 years, respectively. An online calculator was developed to calculate an individual's optimal starting age of screening. Conclusions and Relevance: This study identifies the risk-adapted starting age of breast cancer screening based on the principle of equal management of equal risks, which may inform updates of current screening guidelines.

Uptake of lung cancer screening with low-dose computed tomography in China: A multi-centre population-based study.

Background: Optimal uptake rates of low-dose computed tomography (LDCT) scans are essential for lung cancer screening (LCS) to confer mortality benefits. We aimed to outline the process model of the LCS programme in China, identify the high-risk individuals with low uptake based on a prospective multi-centre population-based cohort, and further explore associated structural characteristics. Methods: A total of 221,955 individuals at high-risk for lung cancer from the National Lung Cancer Screening cohort were included. The logistic regression model was performed to identify the individual characteristics associated with the uptake of LCS, defined as whether the high-risk individual undertook LDCT scans in designated hospitals within six months following the initial risk assessment. The linear regression model was adopted to explore the structural characteristics associated with the uptake rates in 186 communities. Findings: The overall uptake rate was 33·0%. The uptake rate was negatively correlated with the incidence of advanced-stage lung cancer (Pearson's coefficient -0·88, p-value 0·0007). Multivariable regression models found that lower uptake rates were associated with males (OR 0·88, 95%CI 0·85-0·91), current smokers (OR 0·93, 95%CI 0·90-0·96), individuals with depressive symptoms (OR 0·92, 95%CI 0·90-0·94), and the structural characteristics, including longer structural delays in initiating LDCT scans (30-90 days vs. ≤14 days: ß -7·17, 95%CI -12·76∼ -1·57; >90 days vs. ≤14 days: ß -13·69, 95%CI -24·61∼ -2·76), no media-assisted publicity (ß -6·43, 95%CI -11·26∼ -1·60), and no navigation assistance (ß -5·48, 95%CI -10·52∼ -0·44). Interpretation: Multifaceted interventions are recommended, which focus on poor-uptake individuals and integrate the 'assessment-to-timely-screening' approach to minimise structural delays, media publicity, and a navigation assistance along the centralised screening pathway. Funding: Ministry of Finance and National Health Commission of the People's Republic of China.

Sex disparity of lung cancer risk in non-smokers: a multicenter population-based prospective study based on China National Lung Cancer Screening Program.

BACKGROUND: Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females-even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention. METHODS: Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors. RESULTS: With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history. CONCLUSIONS: Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.

One-off low-dose CT for lung cancer screening in China: a multicentre, population-based, prospective cohort study.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the early detection of lung cancer in China. METHODS: A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China, recruiting individuals aged 40-74 years who were asymptomatic for lung cancer with no lung cancer history. Participants were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking, level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer, diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density, lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans. FINDINGS: Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years (IQR 2·8-5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and 143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density was 47·0% higher (hazard ratio 1·47 [95% CI 1·27-1·70]; p<0·0001), lung cancer mortality was 31·0% lower (0·69 [95% CI 0·53-0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57-0·82]; p<0·0001) for participants in the screened group compared with those in the non-screened group. INTERPRETATION: One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with limited medical resources. Further studies are needed to explore interactions by subgroup-including sex, age, smoking status, and economic status-to develop population-specific screening strategies. FUNDING: Ministry of Finance and National Health Commission of the People's Republic of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

BMI changes and the risk of lung cancer in male never-smokers: A prospective cohort study.

BACKGROUND: To investigate the association between the risk of lung cancer and short-term body mass index (BMI) changes in male never-smokers of a large population-based prospective study. METHODS: A total of 37,085 male never-smokers from Kailuan cohort with at least ≥2 BMI measurements were recruited in the present study. The BMI change in the follow-up was calculated as the annual percent change between BMI at last examination and that at baseline, and categorized into five groups: stable (-0.1 to <0.1 kg/m2 /year), minor loss (-1.0 to <0.1 kg/m2 /year) or gain (0.1 to <1.0 kg/m2 /year), and major loss (<-1.0 kg/m2 /year) or gain (≥1.0 kg/m2 /year). The hazards ratios (HRs) and its 95% confidence intervals (CI) were estimated using Cox regression models. RESULTS: During a median follow-up of 5.16 years, 224 lung cancer cases were identified. We found a U-shaped association between BMI changes and lung cancer risk. Compared to men with stable BMI, those with major loss had a nearly twofold higher risk of lung cancer (HR = 1.97, 95% CI: 1.12-3.45), as well as those with major gain had more than twofold higher risk of lung cancer (HR = 2.15, 95% CI: 1.15-4.02). The associations existed when the analysis was stratified by BMI, waist circumference and blood lipids, and lipoproteins concentration at baseline examination. CONCLUSIONS: The dramatic changes in BMI, both gain and loss, might increase lung cancer risk. The control of body weight would be a potential way for lung cancer prevention especially for the nonsmokers.

Lung cancer risk prediction models based on pulmonary nodules: A systematic review.

BACKGROUND: Screening with low-dose computed tomography (LDCT) is an efficient way to detect lung cancer at an earlier stage, but has a high false-positive rate. Several pulmonary nodules risk prediction models were developed to solve the problem. This systematic review aimed to compare the quality and accuracy of these models. METHODS: The keywords "lung cancer," "lung neoplasms," "lung tumor," "risk," "lung carcinoma" "risk," "predict," "assessment," and "nodule" were used to identify relevant articles published before February 2021. All studies with multivariate risk models developed and validated on human LDCT data were included. Informal publications or studies with incomplete procedures were excluded. Information was extracted from each publication and assessed. RESULTS: A total of 41 articles and 43 models were included. External validation was performed for 23.2% (10/43) models. Deep learning algorithms were applied in 62.8% (27/43) models; 60.0% (15/25) deep learning based researches compared their algorithms with traditional methods, and received better discrimination. Models based on Asian and Chinese populations were usually built on single-center or small sample retrospective studies, and the majority of the Asian models (12/15, 80.0%) were not validated using external datasets. CONCLUSION: The existing models showed good discrimination for identifying high-risk pulmonary nodules, but lacked external validation. Deep learning algorithms are increasingly being used with good performance. More researches are required to improve the quality of deep learning models, particularly for the Asian population.

Menstrual factors, reproductive history, and risk of lung cancer: a multi-center population-based cohort study in Chinese females.

BACKGROUND: Female menstrual and reproductive factors, as remarkable indicators of hormone effect, were hypothesized to be associated with lung cancer risk, whereas the existed epidemiological evidence was inconsistent. Our study aims to investigate the association between menstrual and reproductive factors and lung cancer risk based on the Chinese Lung Cancer Screening Program. METHODS: This study was based on a large-scale multi-center population cohort across China recruiting individuals aged 40-74 years old between 2013-2018. Cox regression model was applied to estimate the HRs and 95% CIs. Restricted cubic spline (RCS) analysis was used to estimate dose-response relationships and test for nonlinear associations. RESULTS: Among 553,434 female participants, 1,529 incident lung cancer cases were identified with a median follow-up of 3.61 years. With adjustment for multiple covariates and all significant hormonal factors, elevated lung cancer risk was associated with later age (15, or ≥16 years) at menarche (HR =1.27, 95% CI: 1.04-1.56; HR =1.45, 95% CI: 1.19-1.76), later age (25-29, or ≥30 years) at first live birth (HR =1.27, 95% CI: 1.13-1.43; HR =1.23, 95% CI: 1.00-1.51), and benign breast disease history (HR =1.25, 95% CI: 1.10-1.41). For postmenopausal females specifically, surgical menopause (HR =1.62; 95% CI: 1.29-2.05) and other surgeries on the reproductive system (HR =1.19; 95% CI: 1.01-1.40) both appeared to be predictive of elevated lung cancer risk. Concerning age at menopause, a nonlinear association was observed (P-nonlinear =0.0126). Increased lung cancer risk was observed among females with age at menopause especially above 50. Although we observed no significant associations between longer time (≥13 months) of breastfeeding and lung cancer risk among all participants (HR =0.86; 95% CI: 0.71-1.04), significant decreased adenocarcinoma risk (HR =0.65; 95% CI: 0.53-0.81) was noted among nonsmoking females. CONCLUSIONS: Our findings add some support for the role of menstrual and reproductive factors in lung carcinogenesis. However, these relationships were complex, and required further investigations addressing the biological mechanisms.

Esophageal cancer: Epidemiology, risk factors and screening.

More than 600,000 people are diagnosed with esophageal cancer (EC) every year globally, and the five-year survival rate of EC is less than 20%. Two common histological subtypes of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have great geographical variations in incidence rates. About half of the world's EC was diagnosed in China and a majority of which belong to ESCC. Globally, the overall incidence rate of EC is decreasing. In some high-risk Asian regions, such as China, the incidence rate of ESCC has generally declined, potentially due to economic growth and improvement of diet habits. In some European high-income countries and the United States, the decline is mainly attributed to the decrease in smoking and drinking. The risk factors of EC are not well understood, and the importance of environmental and genetic factors in the pathogenesis is also unclear. The incidence and mortality of advanced EC can be reduced through early diagnosis and screening. White light endoscopy is still the gold standard in the current screening technology. This article reviews the epidemiology, risk factors, and screening strategies of EC in recent years to help researchers determine the most effective management strategies to reduce the risk of EC.

Risk prediction models for esophageal cancer: A systematic review and critical appraisal.

BACKGROUND AND AIMS: Esophageal cancer risk prediction models allow for risk-stratified endoscopic screening. We aimed to assess the quality of these models developed in the general population. METHODS: A systematic search of the PubMed and Embase databases from January 2000 through May 2021 was performed. Studies that developed or validated a model of esophageal cancer in the general population were included. Screening, data extraction, and risk of bias (ROB) assessment by the Prediction model Risk Of Bias Assessment Tool (PROBAST) were performed independently by two reviewers. RESULTS: Of the 13 models included in the qualitative analysis, 8 were developed for esophageal squamous cell carcinoma (ESCC) and the other 5 were developed for esophageal adenocarcinoma (EAC). Only two models conducted external validation. In the ESCC models, cigarette smoking was included in each model, followed by age, sex, and alcohol consumption. For EAC models, cigarette smoking and body mass index were included in each model, and gastroesophageal reflux disease, uses of acid-suppressant medicine, and nonsteroidal anti-inflammatory drug were exclusively included. The discriminative performance was reported in all studies, with C statistics ranging from 0.71 to 0.88, whereas only six models reported calibration. For ROB, all the models had a low risk in participant and outcome, but all models showed high risk in analysis, and 60% of models showed a high risk in predictors, which resulted in all models being classified as having overall high ROB. For model applicability, about 60% of these models had an overall low risk, with 30% of models of high risk and 10% of models of unclear risk, concerning the assessment of participants, predictors, and outcomes. CONCLUSIONS: Most current risk prediction models of esophageal cancer have a high ROB. Prediction models need further improvement in their quality and applicability to benefit esophageal cancer screening.

Crocetin suppresses gestational diabetes in streptozotocin-induced diabetes mellitus rats via suppression of inflammatory reaction.

Gestational diabetes mellitus (GDM) is the serious complication of pregnancy induced via dysfunction in glucose metabolism during the pregnancy. Crocetin already proved antidiabetic effect in streptozotocin (STZ)-induced diabetes mellitus in rats. In this protocol, we have investigated the potential effect of crocetin against STZ-induced GDM in rats. Wistar rats were used for the current protocol; STZ was used for the induction for DM and finally caused the GDM. Body weight and serum advanced glycation end products level were estimated at regular time intervals. We also estimated the fetus weight and placental weight. Biochemical, antioxidant, pro-inflammatory cytokines, inflammatory mediators, and apoptosis parameters were estimated. mRNA expression of NOX2, RAGE, MCP-1, VCAM-1, EGFR, and p65 were also estimated. Crocetin treatment significantly (p < .001) reduced the fetus weight and increased the placental weight and index. Crocetin significantly (p < .001) reduced the blood glucose level and increased the body weight. Crocetin significantly (p < .001) boosted the level of antioxidant enzymes and includes superoxide dismutase, glutathione peroxidase, glutathione, and catalase. Crocetin significantly (p < .001) altered the level of lipid parameters and pro-inflammatory cytokines. Crocetin significantly (p < .001) reduced the level of intercellular adhesion molecule 1, cyclooxygenase-2, and nuclear factor kappa B and increased the level of visfatin against GDM rats. Crocetin significantly (p < .001) altered the level of mRNA expression. Based on the result, we can say that crocetin is a protective drug against the GDM in pregnant rats via antioxidant, inflammatory, and apoptosis parameters. PRACTICAL APPLICATIONS: As we all know, gestational diabetes mellitus (GDM) cases rise all over the world. The current investigation showed the protective effect of crocetin on GDM in experimental rats. The current finding exhibited the protective effect of crocetin against STZ-induced GDM via suppression of inflammatory, oxidative, and apoptosis parameters. The result suggests the antioxidant and anti-inflammatory effect of crocetin. Crocetin can be used as a preventive medication in the treatment of gestational diabetes mellitus, according to the latest findings.

Associations between female lung cancer risk and sex steroid hormones: a systematic review and meta-analysis of the worldwide epidemiological evidence on endogenous and exogenous sex steroid hormones.

BACKGROUND: Published findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women. METHODS: The PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed. RESULTS: Forty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87-0.98) and exogenous (OR: 0.86, 95% CI: 0.80-0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86-0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78-0.99) than in smoking women (OR: 0.98, 95% CI: 0.77-1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74-0.96). CONCLUSIONS: Our meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.