Hongbing Shen

• Professor
• Laboratory Head at Nanjing Medical University

Metabolic disturbance plays a critical role in the initiation of colorectal cancer (CRC), yet the identification of metabolites that are useful for early detection of CRC and its precursor lesions remains elusive. We conducted an untargeted plasma metabolomic profiling by liquid chromatography‐mass spectrometry in a two‐stage case–control study, in...

Lung adenocarcinoma (LUAD) is a heterogeneous disease with substantial genomic differences between individuals of Chinese and European ancestry. Deciphering the timing of driver mutations may lead to insights into tumor evolution that can inform diagnostic and therapeutic approaches for LUAD. Here, we conducted whole-genome sequencing on LUAD sampl...

Intestinal metaplasia (IM) represents a precancerous condition associated with an increased gastric cancer (GC) risk. A better understanding of whether and how precancerous lesions progress to GC is crucial for patient stratification and personalized prevention. Here, we reconstruct evolutionary trajectories of genomic alterations in 330 multi-regi...

Background and Aim The development of accurate noninvasive tests to identify individuals with metabolic dysfunction–associated steatohepatitis (MASH) and liver fibrosis is of great clinical importance. In this study, we aimed to develop 2 noninvasive diagnostic models on the basis of routine clinical and laboratory data, using machine learning, to...

Genome-wide association studies (GWAS) have identified over 50 lung cancer risk loci; however, the precise cellular context of these genetic mechanisms remains unclear due to limitations in bulk tissue eQTL analyses. Here, we present the largest single-cell eQTL atlas of human lung tissue to date, profiling 222 donors using multiplexed scRNA-seq. W...

Lung and gastrointestinal diseases often occur together, leading to more adverse health outcomes than when a disease of one of these systems occurs alone. However, the potential genetic mechanisms underlying lung-gastrointestinal comorbidities remain unclear. Here, we leverage lung and gastrointestinal trait data from individuals of European, East...

Most expression quantitative trait locus (eQTL) analyses have been conducted in heterogeneous gastric tissues, limiting understanding of cell-type-specific regulatory mechanisms. Here, we employed a pooled multiplexing strategy to profile 399,683 gastric cells from 203 Chinese individuals using single-cell RNA sequencing (scRNA-seq). We identified...

Background Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain. Methods and findings We constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the Chi...

Despite significant progress in diagnostic and therapeutic modalities, lung adenocarcinoma (LUAD) still exhibits a high recurrence risk and a low 5‐year survival rate. Reliable prognostic signatures are imperative for risk stratification in LUAD patients. This study encompassed 2740 patients from 23 LUAD cohorts, including one single‐cell RNA seque...

Rationale: The association between fine particulate matter (PM2.5) and lung cancer incidence in non-smokers (LCINS) remains inconsistent. Objectives: To investigate the association between long-term PM2.5 exposure and LCINS in a Chinese population and to assess the modifying effect of genetic factors. Methods: Time-dependent Cox proportional hazard...

Genome-wide association studies have identified thousands of genetic variants associated with non-small cell lung cancer (NSCLC), however, it is still challenging to determine the causal variants and to improve disease risk prediction. Here, we applied massively parallel reporter assays to perform NSCLC variant-to-function mapping at scale. A total...

Introduction: The association between breastfeeding status and early childhood caries (ECC) remains inconclusive. Few studies evaluate the breastfeeding status including both duration and exclusivity according to the WHO recommendations on breastfeeding. This study aimed to investigate the association between breastfeeding status and ECC. Methods...

Background Previous studies predominantly reported that the occurrence of hypomagnesemia was associated with improved cancer prognoses. However, utilizing publicly available data, we demonstrated the presence of bias in this association, attributable to the failure to account for immortal time bias (ITB) when grouping patients based on post-therape...

The role of molecular traits (e.g., gene expression and protein abundance) in the occurrence, development, and prognosis of lung cancer has been extensively studied. However, biomarkers in other molecular layers and connections among various molecular traits that influence lung cancer risk remain largely underexplored. We conducted the first compre...

Background: The fecal immunochemical test (FIT) has been widely used in colorectal cancer (CRC) screening, yet the practical performance of FIT combined with questionnaire-based risk assessment (QRA) remains undetermined. Moreover, risk factors for distinct CRC precursors identified in screening have been rarely compared. Methods: This study was ba...

What is already known about this topic? China is rapidly encountering population aging, yet studies on aging are limited by the traditional aging measure: chronological age, particularly in the field of genomics. Several promising aging measures have been proposed, but they lack comparative evaluation. What is added by this report? PhenoAge was id...

Circulating metabolic profiles have shown promising potential in identifying high‐risk populations for various diseases, while metabolic perturbation plays an important role in gastric cancer. In this study, we conducted a cross‐sectional study with 1800 participants to identify plasma metabolite signatures associated with environmental risk factor...

Background Deficiency in DNA-damage repair (DDR) genes, often due to disruptive coding variants, is linked to higher cancer risk. Our previous study has revealed the association between rare loss-of-function variants in DDR genes and the risk of lung cancer. However, it is still challenging to study the predisposing role of rare regulatory variants...

Autism spectrum disorder (ASD), which is caused by heterogeneous genetic and environmental factors, is characterized by diverse clinical phenotypes linked to distinct pathological mechanisms. ASD individuals with a shared clinical phenotype might contribute to revealing the molecular mechanism underlying ASD progression. Here, it is generated induc...

Background The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative in...

Context Fatty acids (FAs) have emerged as significant contributors to tumorigenesis, yet prospective evidence regarding their specific effects on lung cancer risk remains scarce. Objective To investigate the association between plasma FAs and lung cancer incidence, as well as a potential modification effect of genetic susceptibility on lung cancer...

Background The incidence and mortality of colorectal cancer (CRC) have been steadily rising in many countries. There is an urgent need to identify convenient, reliable biomarkers for CRC early diagnosis and precise prognostic prediction. Methods Untargeted plasma proteomics profiling by liquid chromatography coupled to tandem mass spectrometry was...

Recent genome-wide association studies (GWASs) in liver diseases have generated some polygenic risk scores (PRSs), but their predictive effectiveness on hepatocellular carcinoma (HCC) risk assessment remains unclear. Here, we constructed a novel combined polygenic risk score and evaluated its increment to the well-established risk model. We used 15...

Background Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. Methods This study was performed using the large-scale...

Polygenic risk scores (PRSs) are promising for risk stratification but have mainly been developed in European populations. This study developed single- and multi-ancestry PRSs for lung adenocarcinoma (LUAD) in East Asian (EAS) never-smokers using genome-wide association study summary statistics from EAS (8,002 cases; 20,782 controls) and European (...

Background Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Methods Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) w...

Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack ri...

Background Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Methods Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) wi...

The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop...

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 evalu...

The identification of asymptomatic, non-severe presymptomatic, and severe presymptomatic coronavirus disease (COVID-19) in patients may help optimize risk-stratified clinical management and improve prognosis. This single-center case series from Wuhan Huoshenshan Hospital, China, included 2,980 patients with COVID-19 who were hospitalized between Fe...

Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence...

Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence...

Background Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. Methods We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed i...

Introducción: Understanding risk perception that hinges on health-protective behaviors is central to strategies for prevention. Aim: To classify the pattern of potential risk of worker exposure to SARS-CoV-2, and to assess association with risk perception among non-healthcare workers Methods: In a multi-site, qualitative study, we conducted individ...

Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoki...

Why was the cohort set up? The burden of cancer incidence and mortality is rapidly growing worldwide, with an estimated 19.3 million new cancer cases and nearly 10.0 million cancer deaths occurred in 2020.¹ Over 20% of global cancer cases and almost 30% of global cancer deaths were reported in China,¹ posing an immense burden on Chinese health care...

Background Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non–small cell lung cancer (NSCLC) risk by a two‐stage case‐control design wer...

Why was the cohort set up? Following the success of the first test-tube baby in the UK in 1978, the use of assisted reproductive technology for infertility treatment has increased steadily and resulted in more than 9 million children born after assisted reproductive technology (ART) worldwide.¹,² In China, approximately 15–25% of couples suffer inf...

The proportion of lung cancer in never smokers is rising, especially among Asian women, but there is no effective early detection tool. Here, we developed a polygenic risk score (PRS), which may help to identify the population with higher risk of lung cancer in never‐smoking women. We first performed a large GWAS meta‐analysis (8595 cases and 8275...

Background Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Methods Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) wi...

Graphical abstract

Background The role of genetic background underlying the disparity of relative risk of smoking and lung cancer between European populations and East Asians remains unclear. Methods To assess the role of ethnic differences in genetic factors associated with smoking-related risk of lung cancer, we first constructed ethnic-specific polygenic risk sco...

Background: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival. Metho...

Splicing quantitative trait loci (sQTLs) have been demonstrated to contribute to disease etiology by affecting alternative splicing. However, the role of sQTLs in the development of non-small-cell lung cancer (NSCLC) remains unknown. Thus, we performed a genome-wide sQTL study to identify genetic variants that affect alternative splicing in lung ti...

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 acros...

Household air pollution (HAP) is associated with the development of lung cancer, yet few studies investigated the exposure patterns and joint associations with tobacco smoking. In our study, we included 224 189 urban participants from China Kadoorie Biobank (CKB), 3288 of which diagnosed with lung cancer during the follow‐up. Exposure to four HAP s...

The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants....

Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susc...

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility...

Early‐onset lung cancer is rare with an increasing incidence rate. Although several genetic variants have been identified for it with candidate gene approaches, no genome‐wide association study (GWAS) has been reported. In this study, a two‐stage strategy was adopted: firstly we performed a GWAS to identify variants associated with early‐onset nons...

Rationale: Genome-wide association studies (GWAS) have identified common variants of lung cancer. However, the contribution of rare exome-wide variants, especially protein-coding variants, to cancers remains largely unexplored. Objectives: To evaluate the role of human exomes in genetic predisposition to lung cancer. Measurements and methods:...

Introduction: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. Methods: In this study, we investigated the ass...

Exposure to fine particulate matter (PM2.5) has been reported to be adversely associated with reproductive health. However, current evidence on PM2.5 exposure adversely influencing pregnancy outcomes remains inconclusive. Women receiving assisted reproductive technology (ART) treatment are under close monitoring with regards to their treatment proc...

Background Effective risk prediction models are lacking for personalized endoscopic screening of gastric cancer (GC). We aimed to develop, validate, and evaluate a questionnaire-based GC risk assessment tool for risk prediction and stratification in the Chinese population. Methods In this three-stage multicenter study, we first selected eligible v...

Fine particulate matter (PM2.5) exposure causes DNA mutations and abnormal gene expression leading to lung cancer, but the detailed mechanisms remain unknown. Here, analysis of genomic and transcriptomic changes upon a PM2.5 exposure-induced human bronchial epithelial cell-based malignant transformed cell model in vitro showed that PM2.5 exposure l...

Several recent studies have suggested an association between children conceived by assisted reproductive technology (ART) and a distinct growth pattern in early life, which has been linked to diseases of older age. Telomere shortening, specifically a shorter leukocyte telomere length (LTL), has also been linked to age-related diseases including car...

The utility of the polygenic risk score (PRS) to identify individuals at higher risk of stroke beyond clinical risk remains unclear, and we clarified this using Chinese population-based prospective cohorts. Cox proportional hazards models were used to estimate the 10-year risk, and Fine and Gray's models were used for hazard ratios (HRs), their 95%...

Chronological age only represents the passage of time, whereas biological age reflects the physiology states and the susceptibility to morbidity and mortality. The association between biological age and lung cancer risk remains controversial. Hence, we conducted a prospective analysis in the UK Biobank study and two-sample Mendelian randomization a...

Context Calcium plays a critical role in various physiological activities. However, the association between circulating calcium concentrations and mortality in a general healthy population remains undetermined. Objective To examine the association of serum calcium concentrations with all-cause and cause-specific mortality. Methods Leveraging data...

Background: The relative risk of smoking on lung cancer have been reported to be much higher in white population than that in East Asians. However, it is unknown whether genetic background underlies this disparity between ethnic groups. To assess the role of ethnic differences in genetic factors associated with this phenomenon. Methods: We first co...

Obesity is a leading contributor to colorectal cancer (CRC) risk, but the metabolic mechanisms linking obesity to CRC are not fully understood. We leveraged untargeted metabolomics data from two 1:1 matched, nested case–control studies for CRC, including 223 pairs from the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and...

Background The genetic architectures of colorectal cancer are distinct across different populations. To date, the majority of polygenic risk scores (PRSs) are derived from European (EUR) populations, which limits their accurate extrapolation to other populations. Here, we aimed to generate a PRS by incorporating East Asian (EAS) and EUR ancestry gr...

Lung cancer is one of the most common malignancies in China. Even though smoking was the most important risk factor of lung cancer, only a small fraction of smokers develop lung cancer, which suggested that genetic factors also play an important role in lung carcinogenesis. With the advancement of science and technology, the understanding of the hu...

Objective To examine whether adherence to ideal cardiovascular health (CVH) can mitigate the genetic risk of coronary artery disease (CAD) in non-European populations. Methods Fine and Grey’s models were used to calculate HRs and their corresponding 95% CIs, as well as the lifetime risk of CVH metrics across Polygenic Risk Score (PRS) categories....

Perinatal and childhood adverse outcomes associated with assisted reproductive technology (ART) has been reported, but it remains unknown whether the initial leukocyte telomere length (LTL), which is an indicator of age-related phenotypes in later life, is affected. Here, we estimated the LTLs of 1,137 individuals from 365 families, including 202 c...

Background: Growing evidence indicates the adverse effect of ultra-processed food (UPF) consumption. However, it remains unknown whether UPF consumption influences the risk of colorectal cancer precursors, namely conventional adenomas and serrated lesions. Methods: We drew data from the Nurses' Health Study (NHS), NHS II, and Health Professional...

Epigenome‐wide gene‐gene (G×G) interactions associated with non‐small cell lung cancer (NSCLC) survival may provide insights into molecular mechanisms and therapeutic targets. Hence, we proposed a three‐step analytic strategy to identify significant and robust G×G interactions that are relevant to NSCLC survival. In the first step, among 49 billion...

Cardiogenesis is a tightly regulated dynamic process through a continuum of differentiation and proliferation events. Key factors and pathways governing this process remain incompletely understood. Here, we investigate mice hearts from embryonic day 10.5 to postnatal week 8 and dissect developmental changes in phosphoproteome-, proteome-, metabolom...

To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer (GC), we performed two genome-wide association studies (GWASs) of GC survival in the Jiangsu (N=1049) and Shanghai (N=1405) cohorts. By using a TCGA dataset, we validated genetic markers identified from...

Background and 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. Based on 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...

Background: China has the largest burden of esophageal cancer (EC). Prediction models can be used to identify high-risk individuals for intensive lifestyle intervention and endoscopy screening. However, current models are limited by small sample size and a lack of external validation, and none of them can be embedded into the booming electronic he...

BACKGROUND China has the largest burden of esophageal cancer (EC). Prediction models can be used to identify high-risk individuals for intensive lifestyle interventions and endoscopy screening. However, the current prediction models are limited by small sample size and a lack of external validation, and none of them can be embedded into the booming...

Background Besides featured glucose consumption, recent studies reveal that cancer cells might prefer “addicting” specific energy substrates from the tumor microenvironment (TME); however, the underlying mechanisms remain unclear. Methods Fibroblast-specific long noncoding RNAs were screened using RNA-seq data of our NJLCC cohort, TCGA, and CCLE d...

Background Circulating tumor DNA (ctDNA) has been proven as a marker for detecting minimal residual diseases following systemic therapies in mid-to-late-stage non-small-cell lung cancers (NSCLCs) by multiple studies. However, fewer studies cast light on ctDNA-based MRD monitoring in early-to-mid-stage NSCLCs that received surgical resection as the...

Background: Mosaic chromosomal alterations (mCAs) detected from blood-derived DNA are large structural alterations of clonal haematopoietic origin and are associated with various diseases, such as haematological malignancies, infections, and solid cancers. We aimed to investigate whether mCAs contribute to the risk of lung cancer and modify the ef...

Background Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearit...

Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prognosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study GBM's natural evolutionary trajectory by using rare multifocal samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs an...

Article Analyses of rare predisposing variants of lung cancer in 6,004 whole genomes in Chinese Graphical abstract Highlights d Whole-genome sequencing on 2,984 individuals with non-small cell lung cancer and 3,020 control individuals d Five common and low-frequency loci identified based on high-quality haplotype reference d Rare loss-of-function v...