[Association between chronic lung diseases and the risk of lung cancer in UK Biobank: observational and Mendelian randomization analyses].

Objective: To investigate the association between chronic lung diseases and the risk of lung cancer. Methods: Using UK Biobank (UKB) survey data, 472 397 participants who had not previously been diagnosed with cancer and whose self-reported sex was consistent with their genetic sex were studied. Information on the prevalence of previous chronic lung diseases, general demographic characteristics and the prevalence of lung cancer was collected using baseline questionnaires and national health system data. The multivariate Cox proportional risk regression model was used to analyze the association between four previous chronic lung diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and interstitial pulmonary disease) and the risk of lung cancer. A total of 458 526 participants with genotype data in the observational study were selected as research objects, and the closely related and independent genetic loci with four chronic lung diseases were selected as instrumental variables, and the association between four chronic lung diseases and the risk of lung cancer was analyzed by Mendelian randomization (MR). The dose-response relationship between genetic risk score and the risk of lung cancer in different chronic lung diseases was evaluated using a restricted cubic spline function. Results: The age [M (Q1, Q3)] of the subjects was 57 (50, 63) years old, and there were 3 516 new cases of lung cancer (0.74%) during follow-up. The multivariate Cox proportional hazard regression model analysis showed that previous chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, about 1.61 (1.49-1.75) and 2.61 (1.24-5.49), respectively. MR Studies showed that genetically predicted chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, with HR (95%CI) of 1.10 (1.03-1.19) and 1.04 (1.01-1.08), respectively. The results of restricted cubic spline function analysis showed that the risk of lung cancer increased linearly with the increase of genetic risk scores for chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (P<0.05). Neither observational studies nor Mendelian randomization analysis found an association between previous asthma or interstitial lung disease and the risk of lung cancer (both P values>0.05). Conclusion: Chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are potential risk factors for lung cancer.

[Multi-omics approaches for revealing the etiology of cancer: from genomics, exposomics, metabolomics to system epidemiology].

Identifying risk factors of the disease are one of the main tasks of epidemiology. With the advancement of omics technologies (e.g., genome, transcriptome, proteome, metabolome, and exposome), cancer etiology research has entered the stage of systems epidemiology. Genomic research identifies cancer susceptibility loci and uncovers their biological mechanisms. Exposomic research investigates the impact of environmental factors on biological processes and disease risks. The metabolome is downstream of biological regulatory networks, reflecting the effects of the gene, environment, and their interactions, which can help elucidate the biological mechanisms of genetic and environmental risk factors and identify new biomarkers. Here, we reviewed the applications of genomic, exposomic, and metabolomic studies in the etiologic research on cancer. We summarized the importance of multi-omics approaches and systems epidemiology in cancer etiology research and outlined future perspectives.

[Mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence].

Objective: To evaluate the possible mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence. Methods: After excluding individuals with missing educational levels and cancer information at baseline, 446 772 participants in the UK Biobank (UKB) prospective cohort study were included. Cox regression models were used to investigate the associations of educational level and smoking and healthy diet score with the incidence of lung cancer. Mediating effect analysis was conducted to analyze the mediating effect of smoking and healthy diet score on the correlation between educational level and lung cancer. Results: During a median follow-up of 7.13 years, 1 994 new- onset lung cancer cases were observed. Per 1 standard deviation (5 years) increase in educational level was associated with a 12% lower risk of lung cancer (HR=0.88, 95%CI: 0.84-0.92). The corresponding level 1-5 in the International Standard Classification for Education (ISCED) were mapped to UKB self-report highest qualification to estimate the educational level. A higher rank means a higher educational level. Compared with level ISCED-1, the HR(95%CI) of level ISCED-2, ISCED-3, ISCED-4 and ISCED-5 were respectively 0.83 (0.72-0.94), 0.67 (0.53-0.85), 0.76 (0.65-0.89) and 0.72 (0.64-0.80) for lung cancer. Education years were negatively correlated with smoking, with ß coefficients (95%CI) being -0.079 (-0.081- -0.077), but positively correlated with healthy diet score (ß=0.042, 95%CI: 0.039-0.045). Analysis of mediating effect indicated that the association of educational level with lung cancer risk was mediated by smoking and healthy diet score, the proportions of mediating effect were 38.952% (95%CI: 31.802%-51.659%) and 1.784% (95%CI: 0.405%-3.713%), respectively. Conclusion: Smoking and healthy diet score might mediate the effect of educational level on the incidence of lung cancer, indicating that improving the level of education can reduce the risk of lung cancer by changing lifestyles such as smoking and diet.

[Rethinking of institutional reform and development of disease control and prevention system in post COVID-19 epidemic era in China].

The problems and shortcomings revealed in our response to COVID-19 epidemic have suggested us to take measures to improve the disease control and prevention system of China. For the reform and development of China's disease control and prevention institution in the new era,we need to rethink the function orientation of the disease control and prevention institution, the key and difficult points in institutional mechanism reform and the building of core competence and essential capacity of disease control and prevention system.

[Polygenic risk score in personalized screening of lung cancer: a prospective cohort study in Chinese].

Objective: To explore how to personalize lung cancer screening programs for prevention in Chinese populations based on individual genetic risk score. Methods: We constructed the lung cancer polygenic genetic risk score (PRS-19) based on the 19 previously published genetic variations, using 100 615 participants with genotyping data from the China Kadoorie Biobank (CKB). Using the 5-year absolute risk of lung cancer in a population (55 years old with at least 30-pack-year history of smoking) as reference, the trend of 5-year absolute risk in different genetic risk groups was calculated in smokers and non-smokers, respectively. Distribution curves of 5-year absolute risk were also described to determine the theoretical age or smoking dose when different genetic risk groups reached the reference values. Given the overall findings, the specific start age for lung cancer screening were suggested for different genetic risk groups. Results: The 5-year absolute risk of lung cancer was 0.67% in 55-year-old smokers with 30 packs per year in the CKB. Among smokers, 5-year absolute risk of participants increased as the genetic risk increased. Hence, it was recommended that people at high genetic risk should start screening earlier. For the highest genetic risk populations (the top 1% of PRS), the start age might be changed to 50 years old. If the start age remained at 55-year-old, the smoking dose should be set lowered in high genetic risk populations. For the highest genetic risk populations, they should be included in lung cancer screening regardless of the cumulative smoking exposure. Among nonsmokers, it was also valuable to screen people with high genetic risk, considering the start age of 62 for the highest genetic risk populations and 74 for the lowest genetic risk populations (the bottom 5% of PRS). Conclusions: PRS-19 can be effectively used in developing lung cancer screening program for individualized prevention in China. For smokers with high genetic risk, the recommended starting age and smoking dose could be lowered for lung cancer screening, and non-smokers with high genetic risk could also be included in the screening programs.

[Profile of China National Birth Cohort].

With the rapid changes in lifestyle, natural and social environment, the reproductive health status of couples in childbearing age continues to decline, and long-term outcomes of the rapidly increasing offspring conceived by assisted reproductive technology (ART) needs to be evaluated urgently. Therefore, the focus of research now needs to be extended from death and severe diseases to full life cycle and full disease spectrum. In order to meet the demand for such research, we launched the China National Birth Cohort (CNBC) study, an ongoing prospective and longitudinal study aiming to recruit 30 000 families underwent ART and 30 000 families with spontaneous pregnancies. Long-term follow-up programs will be conducted for both spouses and their offspring. Data of couples and their offspring, such as environmental exposure, reproductive history, psychological and behavioral status, will be collected during follow-up. Peripheral blood, urine, umbilical blood, follicular fluid, semen were also collected at different follow-up nodes. Based on high-quality data and biological samples, CNBC will play an extremely important supporting role and have a far-reaching impact on maternal and children's health care and reproductive health in China. This paper is exactly a brief introduction to the construction and basic design of CNBC.

[Quality control and measures of China National Birth Cohort].

Birth cohort is an effective method to explore the relationship between various prepregnant and pregnant exposures and the health of fetuses, infants and young children. It is a long construction period to build a birth cohort and the quality of research may be affected by many factors. This paper reviews the quality assurance and quality control measures in the process of China National Birth Cohort (CNBC), and summarizes the construction experience. We aim to provide experience for related cohort studies, which could improve the quality of cohort studies through removing the impact of related factors. CNBC adopted a series of measures to ensure the quality of research in the top-level design of quality assurance, including screening research center, developing member management system, formulating standard operating procedures and training staff by it. In terms of quality control, it includes real-time, timely and timing quality control for the process of data generation, full-cycle quality control for biological sample collection, processing, storage and comprehensive three-dimensional quality control for staff training, supervision and quantitative assessment.

[Baseline characteristics of the participants of China National Birth Cohort].

Objective: To explore the effects of environmental, genetic factors as well as the interactions in early life on the short-term and long-term health of offspring and to systematically evaluate the pregnancy outcomes and health of offspring after birth between families with assisted reproductive technology (ART) conception and families with spontaneous conception. Methods: The China National Birth Cohort (CNBC), a multicenter prospective birth cohort study, includes both families with ART conception and families with spontaneous conception. Since 2016, CNBC has recruited families from 24 hospitals located in 12 provinces, municipalities and autonomous regions throughout China. Information and biospecimens were collected before ART treatment, embryo transfer, at early, second, third trimester and delivery, and at 42 days, 6, 12 and 36 months after birth. Results: By June 2020, CNBC had included 27 044 families with ART conception and 29 589 families with spontaneous conception. The majority of the participants are urban residents. Among the families with ART conception, 65.5% of the men and 63.7% of the women had college degrees or higher. The mean age distribution of men and women was (33.83±5.52) and (32.38±4.67) years. 83.2% of women were primiparas, and the prevalence rates of current regular smokers and current alcohol drinkers were 0.8% and 2.1% in women. Among the families with spontaneous conception, 81.5% of the men and 86.5% of the women had college degrees or higher. The mean age distribution of men and women was (32.06±5.09) and (30.40±4.27) years. 67.2% of women were primiparas, and the prevalence rates of current regular smokers and current alcohol drinkers were 0.1% and 2.2% in women. The baseline characteristics were different between the families with ART conception and spontaneous conception in different regions. Conclusion: CNBC provides a powerful and rich resource in studying the impact of genetic, environmental factors and interactions in early life and ART treatment on the health of offspring after birth.

[Application of cloud-based information platform in China National Birth Cohort].

Birth cohort is an important observational study which can continuously and dynamically collect the exposure changes and health outcomes from gametophyte development to adolescence and even old age. However, because of its complex design and difficult implementation, how to construct birth cohort with high quality and high efficiency is the main difficulty faced by epidemiologists at home and abroad. In 2016, China National Birth Cohort was officially launched. The network and information technology were used to explore, and a set of "cloud-based information platform" was established to support this queue construction, containing 16 units in China. After four years of development, the platform has formed a complete set of programs about the construction of cohort information platform, which including recruitment and follow-up management of participants, real-time data interaction, queue quality control, multi-level authority management and function division. The relevant design framework and functional elements provide the references to the future information construction of large-scale birth cohort and even population-based research in China.

[The Autism Spectrum Disorder Cohort-the sub-cohort of China National Birth Cohort].

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

[A sub-cohort study design of the maternal and infant microbes in China National Birth Cohort].

The importance of gut microbes to human health has gradually attracted attention. With the use of animal models, it has been revealed that maternal microbes during pregnancy could influence their children's health outcomes through shaping their microbial composition and regulating the development of their metabolic and immune system. However, the physiological mechanism of the human body is more complex and is affected by the interaction of multiple factors. The research results obtained from animal models are often inconsistent with human studies. At present, the influence of maternal intestinal microbes during pregnancy on the microbial colonization in their offspring and on a series of children's health outcomes is still unclear. Establishing a sub-cohort to detect the microbiome of the women across pregnancy and of their offspring, and further to integrate with variety of environmental and behavioral exposures can better provide reliable support for the research on the mechanism of children's health and diseases. This paper briefly introduces the research objectives, content, progress, strength and limitations of the sub-cohort study.

[Association between polygenic risk score and age at onset of gastric cancer].

Objective: To explore the association between polygenic risk score (PRS) and age at onset and early-onset risk of gastric cancer (GC). Methods: Gastric cancer cases from existing genome-wide association study were included, and 112 single nucleotide polymorphisms associated with GC risk were used to derive individual PRS. Analysis of variance and Pearson correlation test was used to depict the relationship between PRS and GC onset age. Cases diagnosed before 50 years old were defined as early-onset gastric cancer. Cox proportional hazard model was used to test the association between PRS and early-onset GC risk with early-onset age as the timescale and low genetic risk (PRS ≤20%) as the reference group. Results: A total of 8 629 cases, including 6 284 males (72.82%) and 2 345 females (27.18%), were included, and the mean age was (60.61±10.80) years old. The PRS was negatively correlated with age of GC onset (r=-0.05, P<0.001). The mean age of gastric cancer cases with low, intermediate, and high genetic risk were (61.68±10.33), (60.53±10.79), (59.80±11.20), respectively. PRS was significantly associated with the risk of early-onset GC in a dose-response manner (intermediate genetic risk: HR=1.19, 95%CI: 1.03-1.39, P=0.022; high genetic risk: HR=1.44, 95%CI: 1.20-1.71, P<0.001). Conclusions: PRS may contribute to the risk of both GC and early-onset GC. PRS can be used as a measurable indicator for risk prediction for occurrence and early-onset of GC.

[Progress in metabolomics epidemiology].

In recent years, with the rapid development of metabonomic technology and analytic methods, metabolomics epidemiology, as an important branch of systems epidemiology, attracts more attention. Metabolomics epidemiology can better describe the characteristics of exposure, reflect the interaction between environmental factors and genetics, uncover the "black box" of the mechanisms underlying exposure and disease, and identify new biomarkers. This article briefly introduces the definition, methods, and progress of metabolomics epidemiology.

[Advance on theoretical epidemiology models research of prevention and control of COVID-19].

COVID-19 has brought a significant impact to the global health system, and also opportunities and challenges to epidemiological researches. Theoretical epidemiological models can simulate the process of epidemic in scenarios under different conditions. Therefore, modeling researches can analyze the epidemical trend of COVID-19, predict epidemical risks, and evaluate effects of different control measures and vaccine policies. Theoretical epidemiological modeling researches provide scientific advice for the prevention and control of infectious diseases, and play a crucial role in containing COVID-19 over the past year. In this study, we review the theoretical epidemiological modeling researches on COVID-19 and summarize the role of theoretical epidemiological models in the prevention and control of COVID-19, in order to provide reference for the combination of mathematical modeling and epidemic control.

[China guideline for the screening and early detection of female breast cancer(2021, Beijing)].

Breast cancer is the commonest malignant tumor among Chinese females, ranking first in terms of incidence of female cancers. Commissioned by the Disease Prevention and Control Bureau of National Health Commission of the People's Republic of China, the National Cancer Center formulated the Guideline for Screening and Early Diagnosis and Treatment of Female Breast Cancer in China according to WHO Handbook for Guideline Development. The methods on Cochrane China were referred to for the formulation of the system evaluation procedures. The GRADE methods for assessment, formulation and evaluation were adopted for the classification of evidence quality and recommendation strength, and the items were reported according to Reporting Items for Practice Guidelines in Healthcare. Based on the results of evaluation, the guideline gives evidence-based recommendations for the appropriate population and technical procedures for breast cancer screening and early diagnosis and treatment after comprehensive consideration of China's national conditions, the advantages and disadvantages of the evidence, the quality of the evidence, the economic cost of screening, the feedback of multidisciplinary clinical research respondents, and in-person expert consensus. It is aimed at regulating the practices of female breast cancer screening and early diagnosis and treatment and enhancing the effectiveness of the prevention and control of female breast cancer in China.

[China guideline for the screening and early detection of lung cancer(2021, Beijing)].

In China, the malignant tumor with the highest incidence and motality is lung cancer (LC). As screening and early detection and treatment are effective in reducing LC mortality, formulating a guideline in line with China's national conditions for the screening and early detection and treatment of LC will greatly promote the homogeneity and accuracy of LC screening, and result in an improvement of the effectiveness of LC screening. Commissioned and directed by the Disease Prevention and Control Bureau of the National Health Commission of the People's Republic of China, the guidline was initiated by the National Cancer Center of China and formulated with joint effort by experts from different disciplines. Following the principles and methods in WHO Handbook for Guideline Development, the guidline integrates the latest development in LC screening and early diagnosis and treatment worldwide while fully considering China's national conditions and practical experience in LC screening. It provides detailed evidence-based recommendations for different aspects of LC screening, such as the targeted population, the technologies and the procedures, to regulate the practices of LC screening and early diagnosis and treatment and enhance the effectiveness of the prevention and control of LC in China.

[Epidemiological research in the big data era: opportunities, challenges and prospectives].

Recent years with the rapid progress in high-throughput omics techniques, the accumulation of population cohorts and biobanks, great advances in internet and information technology, and the emerging tools for big data utilization, health care big data provide abundant data resources and broad research platforms for epidemiological research. We aimed to review the opportunities and challenges of epidemiological research in the era of big data, and explore the future development of epidemiology. Epidemiology should seize the opportunities, open up new directions, develop new methods, and promote the translation of research results into public health and clinical medicine, which will eventually realize the vision of "Healthy China".

[Challenges and factors that influencing causal inference and interpretation, based on Mendelian randomization studies].

Genetic variation is used as instrumental variable to investigate the causal relationship between exposure and outcome, which can avoid issues of confounding and reserve causation regarding Mendelian randomization studies. However, the instrumental variables in Mendelian randomization studies must satisfy three core assumptions-the relevance assumption, the independence assumption, and the exclusion restriction assumption. In addition to the plausibility of core assumptions, the application of Mendelian randomization studies in causal inference is also subject to other limitations. Findings from the Mendelian randomization studies should be interpreted in the context of existing evidence from other sources. In this article we provide an overview of the assumptions, limitations, and interpretation on causal inference that related to Mendelian randomization studies that can be applied in studies of the same kind.

[Principles of dynamics model and its application in forecasting the epidemics and evaluation the efforts of prevention and control interventions].

During the epidemics of COVID-19 in domestic China and recently continuing rapid spread worldwide, a bunch of studies fitted the epidemics by transmission dynamics model to nowcast and forecast the trend of epidemics of COVID-19. However, due to little known of the new virus in early stage and much uncertainty in the comprehensive strategies of prevention and control for epidemics, majority of models, not surprisingly, predict in less accuracy, although the dynamics model has its great value in better understanding of transmission. This comment discusses the principle assumptions and limitations of the dynamics model in forecasting the epidemic trend, as well as its great potential role in evaluating the efforts of prevention and control strategies.

[Construction of urban scale-free network model and its epidemiological significance in the prevention and control of COVID-19].

COVID-19 is a public health emergency currently. In this study, a scale-free network model is established based on the Spring Migration data in 2020.The cities is clustered into three different modules. The epidemic of the cities in the black module was the most serious, followed by the red and the cyan. The black module contains 9 cities in Zhejiang province and 8 cities in Guangdong province, most of them located in the southeast coastal economic belt. These cities should be the key cities for epidemic prevention and control.