OBJECTIVES:An increasing trend of pancreatic cancer in young adults has emerged in some countries. This study aimed to investigate global trends of pancreatic cancer in young adults and explore the impact of exposure to risk factors on pancreatic cancer incidence during youth. METHODS:Global and national data on pancreatic cancer incidence, disability-adjusted life-years, attributive mortality, and summary exposure values of risk factors were retrieved from the Global Burden of Disease 2019. The average annual percent change (AAPC) of incidence and mortality was calculated. Additionally, generalized additive models were applied to explore the non-linear associations between the levels and changes in the Human Development Index and AAPC. RESULTS:Global pancreatic cancer incidence increased during various periods from 1990 to 2019, particularly in adults aged <45 years from 2010 to 2019, at an average annual increase rate of 0.7% (95% confidence interval: 0.4-1.0%). The AAPC of early-onset pancreatic cancer incidence from 2010 to 2019 was negatively correlated with Human Development Index levels in both 2010 and 2019 but positively correlated with Human Development Index acceleration. Significant increases in early-onset pancreatic cancer incidence were observed over this period in 32 of 88 countries, primarily in South America, North America, Oceania, and Africa. Early-onset pancreatic cancer mortality attributed to high body mass index and fasting plasma glucose increased, while that attributed to tobacco use declined. CONCLUSIONS:An increasing trend has emerged in the global incidence and burden of early-onset pancreatic cancer over the last few decades. This rise may partly be attributed to global epidemics of high body mass index and fasting plasma glucose.

Background:Evidence on the long-term benefits and cost-effectiveness of colorectal cancer (CRC) screening strategies in China remains limited. This modelling study aims to address this issue for various CRC screening strategies in China between 2020 and 2060. Methods:Using a previously developed microsimulation model (MIMIC-CRC) with Chinese epidemiological data, we evaluated four CRC screening strategies targeting population aged 45-74 years: no screening, colonoscopy every 10 years, biennial faecal immunochemical testing (FIT), and a roll-out FIT screening strategy. Screening coverage (invitation) rates from 5% to 100% were analysed. Single-cohort analysis of 100,000 individuals was conducted to estimate the relative cost-effectiveness of each strategy. A multiple-cohort analysis of 100,000 people aged 40+ over 2020-2060 was conducted to project nation-wide long-term benefits and cost-effectiveness. Findings:In single-cohort analysis, all strategies yielded reductions in CRC incidence and mortality compared to no screening, with colonoscopy outperforming FIT-based strategies at the same invitation rates. In multiple-cohort analysis, among people over 40 years of age in China over 2020-2060, compared to no screening, at invitation rate of 5%, screening by colonoscopy, biennial FIT and roll-out FIT-based approach were estimated to avert 1.2, 0.4, and 0.3 million incident CRCs and 0.2, 0.1, and 0.1 million CRC-related deaths, respectively, compared to no screening (25.4 million incident CRCs and 4.4 million CRC-related deaths), and this preventive effect enlarged as the screening coverage rate increased. At full coverage, colonoscopy achieved the largest reductions (38.2% lower incidence and 43.2% lower mortality) but required the most resources. Biennial FIT and roll-out FIT-based approach screening was slightly less effective but had significant reduced colonoscopy needs (reduction of 83.8% and 85.2%, respectively) and overall cost (reduction of 23.4% and 37.8%, respectively) compared to colonoscopy screening. Interpretation:Nation-wide implementation of screening would be effective in reducing the burden of CRC in China. Biennial FIT and roll-out FIT-based screening strategies could prevent incident CRC cases and CRC-related deaths with considerably fewer resources than colonoscopy screening. Efforts should be made to increase the screening coverage in China. Funding:Chinese Academy of Medical Science Innovation Fund for Medical Science (2022-I2M-1-0031); National Natural Science Foundation of China (82173606; 82273726); Beijing Nova Program of Science and Technology (20230484397).

Background: The incidence of early-onset colorectal cancer (EOCRC), which exhibits differential clinical, pathological, and molecular features compared to late-onset CRC (LOCRC), is rising globally. The potential differential effects of blood glucose on EOCRC compared to LOCRC have not been investigated. Methods: This study analyzed 374,568 participants from the UK Biobank cohort and 172,809 participants from the Kailuan cohort. The linear associations between blood glucose and EOCRC/LOCRC were estimated using Cox regression models. Restricted cubic spline (RCS) analysis and non-linear Mendelian randomization (MR) analysis using a 70-SNPs genetic instrument for fasting glucose were used to explore the potential non-linear associations. Results: Participants in the highest quintile of blood glucose had higher overall CRC risk compared to the lowest quintile (HR = 1.10 in the UK Biobank cohort, 95% CI: 1.01-1.21, P-trend = 0.012; HR = 1.23 in the Kailuan cohort, 95% CI: 1.01-1.51, P-trend = 0.036). Elevated glucose ( > 7.0 mmol/L) was more strongly associated with increased risk of EOCRC (HR = 1.61, 95% CI: 1.07-2.44) than with LOCRC (HR = 1.14, 95% CI: 1.02-1.27) in the UK Biobank cohort ( P- heterogeneity = 0.014). Elevated glucose ( > 7.0 mmol/L) was associated with increased risk of LOCRC (HR = 1.25, 95% CI: 1.04-1.65) in the Kailuan cohort as well. There was no evidence for non-linear associations between blood glucose and risks of EOCRC/LOCRC. Conclusions: This study showed a positive association between blood glucose and CRC risk in a dose-response manner, particularly for EOCRC, suggesting that tighter glucose control should be a priority for younger age groups.

BACKGROUND & AIMS: The screening yield and related cost of a risk-adapted screening approach compared with established screening strategies in population-based colorectal cancer (CRC) screening are not clear.METHODS: We randomly allocated 19,373 participants into 1 of the 3 screening arms in a 1:2:2 ratio: (1) one-time colonoscopy (n = 3883); (2) annual fecal immunochemical test (FIT) (n = 7793); (3) annual risk-adapted screening (n = 7697), in which, based on the risk-stratification score, high -risk participants were referred for colonoscopy and low-risk ones were referred for FIT. Three consecutive screening rounds were conducted for both the FIT and the risk-adapted screening arms. Follow-up to trace the health outcome for all the participants was conducted over the 3 -year study period. The detection rate of advanced colorectal neoplasia (CRC and advanced precancerous lesions) was the main outcome. The trial was registered in the Chinese Clinical Trial Registry (number: ChiCTR1800015506).RESULTS: In the colonoscopy, FIT, and risk-adapted screening arms over 3 screening rounds, the partici-pation rates were 42.4%, 99.3%, and 89.2%, respectively; the detection rates for advanced neoplasm (intention-to-treat analysis) were 2.76%, 2.17%, and 2.35%, respectively, with an odds ratio (OR)colonoscopy vs FIT of 1.27 (95% confidence interval [CI]: 0.99-1.63; P = .056), an ORcolonoscopy vs risk-adapted screening of 1.17 (95% CI, 0.91-1.49; P = .218), and an ORrisk-adapted screening vs FIT of 1.09 (95% CI, 0.88-1.35; P = .438); the numbers of colonoscopies needed to detect 1 advanced neoplasm were 15.4, 7.8, and 10.2, respectively; the costs for detecting 1 advanced neoplasm from a government perspective using package payment format were 6928 Chinese Yuan (CNY) ($1004), 5821 CNY ($844), and 6694 CNY ($970), respectively. CONCLUSIONS: The risk-adapted approach is a feasible and cost-favorable strategy for population-based CRC screening and therefore could complement the well-established one-time colonoscopy and annual repeated FIT screening strategies. (Chinese Clinical Trial Registry; ChiCTR1800015506).

Screening and early diagnosis and treatment have been proven effective in reducing the incidence and mortality of colorectal cancer. Colonoscopy combined with pathological examination is the gold standard for colorectal cancer screening. However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits. Additionally, it describes the current situation of colorectal cancer screening in China and summarizes the challenges faced in colorectal cancer screening in order to optimize the FIT-based colorectal cancer screening strategies in the population and provide theoretical reference for effective colorectal cancer screening.

Objective To evaluate the feasibility and effectiveness of colonoscopy, fecal immunochemical test(FIT) and risk-adapted screening strategies in population-based colorectal cancer screening. Methods Based on the randomized controlled trial of colorectal cancer screening(TARGET-C) which was carried out in 6 centers of 5 provinces in China from May 2018 to May 2021, the participants who met the inclusion criteria of the study were randomly assigned to one of the following screening intervention groups in a ratio of 1∶2∶2, which were colonoscopy group, FIT group and risk-adapted screening group(participants evaluated to be at high risk were recommended to undertake colonoscopy, those at low risk were recommended to undertake FIT and FIT positive people received colonoscopy). The 3 groups received different schemes of colorectal cancer screening, in which the colonoscopy group only received baseline screening, whereas the FIT group and the risk-adapted screening group received annual follow-up screening on the basis of baseline screening. The main outcome was the detection rate for advanced colorectal neoplasm(including colorectal cancer and advanced adenoma). The participation rate, detection rate for any neoplasm and resource load of colonoscopy among different screening groups were further analyzed. Results A total of 19 373 participants meeting the inclusion and exclusion criteria were enrolled, including 8082 males(41.7%) and 11 291 females(58.3%), with an average age of (60.5±6.5) years. Among them, 3883 were in the colonoscopy group, 7793 in the FIT group, and 7697 in the risk-adapted screening group. After 1 or 3 rounds of screening(2 rounds of follow-up screening completed in FIT group and risk-adapted screening group), the overall participation was the highest for the FIT group(99.3%), followed by the risk-adapted screening group(89.2%) and the coloscopy group(42.3%). According to the intention-to-treat analysis, the detection rates of advanced neoplasm in the colonoscopy group was higher than that in the FIT group(2.76% vs. 2.17%, ORcolonoscopy vs FIT=1.30, 95% CI: 1.01-1.65, P=0.037); there were no statistically significant differences regarding the detection rates of advanced neoplasm between the colonoscopy group and the risk-adapted screening group(2.76% vs. 2.35%, ORcolonoscopy vs risk-adapted screening=1.19, 95% CI: 0.93-1.51, P=0.156), and between the risk-adapted screening group and the FIT group(2.35% vs. 2.17%, ORrisk-adapted screening vs FIT=1.09, 95% CI: 0.88-1.34, P=0.440). The number of colonoscopies needed to be performed to detect one advanced neoplasm was used as an indicator to evaluate the resource load of colonoscopy. The number was the highest for the coloscopy group(15.4), followed by the risk-adapted screening group(10.2) and the FIT group(7.8). Conclusions The risk-adapted screening strategy is feasible and effective in population-based colorectal cancer screening, and could serve as an effective supplement to the traditional colonoscopy and FIT-based colorectal cancer screening strategies.

Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.

Background Evidence of temporal changes in the gut microbiome and circulating metabolome alterations in colorectal precancerous lesions before and after treatment is sparse. We, therefore, aimed to investigate the fecal microbial and plasma metabolomic signatures associated with colorectal adenomas and their temporal changes in advanced colorectal adenomas (AA) before and after polypectomy. Methods We included 386 AAs, 324 patients with non-advanced adenoma (NAA), and 329 healthy controls (HC) in a population-based colorectal cancer screening trial. A sub-cohort of 84 AAs who underwent polypectomy at baseline had repeated colonoscopies after two years. All fecal and plasma samples were collected before diagnosis. Omics markers were identified using metagenomics and metabolomics data with validations in the open-source dataset. Temporal changes in AA-related omics signatures were compared in 84 AAs between baseline and two-year after polypectomy (IDDF2023-ABS-0104 Figure 1 (A) Diagram of the study design and data collection (B) Workflow of data analyses). Results We identified elevated abundances of Bacteroides xylanisolvens, Parabacteroides merdae, Parabacteroides distasonis, Flavonifractor plautii, Clostridium symbiosum, and Bacteroides intestinalis in AAs (IDDF2023-ABS-0104 Figure 2. Characteristic of fecal microbiome in AAs, NAAs and HCs (species level). (A) Alpha diversity indices; (B) Gut microbiome similarities; (C-D) Comparisons of gut microbial species between AAs and HCs/NAAs; (E) Log10-transformed relative abundances of the nine differential species), which remained at the same level two-year after polypectomy (p>0.05), as well as nearly half of the AA-related plasma metabolites. We further constructed gut microbial species- and plasma metabolite-based prediction models for AA. However, risks predicted by AA-related gut microbial and plasma metabolic signatures were stable in AAs before and two-year after polypectomy (IDDF2023-ABS-0104 Figure 3. Risks of AA predicted by AA-related gut microbial species and plasma metabolites in AA patients who had no findings of adenoma in repeated colonoscopies (A), or who were diagnosed with NAA in repeated colonoscopies (B), or who were diagnosed with AA in repeated colonoscopies (C)). Conclusions Gut microbial signatures associated with AA remained stable for two years after polypectomy, indicating the significance of gut microbiota reconstruction in CRC prevention.

Objective: To evaluate the participation rate and detection of colorectal neoplasms based on annual fecal immunochemical testing (FIT) for three consecutive years in a population-based colorectal cancer screening program in China. Methods: Based on a population-based colorectal cancer screening program conducted from May 2018 to May 2021 in 6 centers in China, 7 793 eligible participants aged 50-74 were included and offered free FIT and colonoscopy (for those who were FIT-positive on initial screening). At baseline, all participants were invited to receive FIT. In subsequent screening rounds, only FIT-positive participants who did not undergo colonoscopy or FIT-negative participants were invited to have repeated FIT screening. FIT-positive participants were recommended to undertake colonoscopy and pathological examination (if abnormalities were found during colonoscopy). An overall of three rounds of annual FIT screening were conducted. The primary outcomes of the study were the participation rate of FIT screening, the compliance rate of colonoscopy for FIT-positive participants, and the detection rate of colorectal neoplasms. Results: Among the 7 793 participants included in this study, 3 310 (42.5%) were male, with age of (60.50±6.49) years. The overall participation rates for the first, second and third round of FIT screening were 94.0%(7 327/7 793), 86.8% (6 048/6 968) and 91.3% (6 113/6 693), respectively. Overall, 7 742 out of 7 793 participants (99.3%) attended at least one round of screening, and 5 163 out of 7 793 participants (66.3%) attended all three rounds of screening. The positivity rate was significantly higher in the first (14.6%, 1 071/7 327) round compared with the second (5.6%, 3 41/6 048) and third (5.5%, 3 39/6 113) screening rounds (P<0.001). The overall compliance rates of colonoscopy examination among FIT-positive subjects were over 70% in three rounds, which were 76.3% (817/1 071), 75.7% (258/341) and 71.7% (243/339), respectively. In a multivariate logistic regression model considering factors including sex, education background, smoking, alcohol drinking, previous colonoscopy examination, colonic polyp history and family history of colorectal cancer among first-degree relatives, gender and smoking status were related factors affecting the participation rate of FIT screening, with higher rate in males and non-smokers. In addition, logistic regression analysis also found that age was negatively correlated with the compliance rate of colonoscopy in FIT positive patients. The detection rate of advanced tumors (colorectal cancer + advanced adenoma) declined from the first round to subsequent rounds [1st round: 1.15% (90/7 793); 2nd round: 0.57% (40/6 968); and 3rd round: 0.58% (39/6 693)], however, the positive predictive value for advanced neoplasms increased round by round, and was 11.02% in the first screening round, 15.50% in the second screening round, and 16.05 % in the third screening round. In each screening round, the detection rate for advanced neoplasms was higher in men than that in women, and increased with age. Conclusions: Annual repeated FIT screening has high acceptance and satisfying detection rates in the Chinese population. To optimize and improve the effectiveness of colorectal cancer screening, multi-round repeated FIT screening should be implemented while ensuring high participation rates.

Neoadjuvant immunotherapy has significantly changed the therapeutic approach for treating patients with surgically resectable non-small cell lung cancer (NSCLC). Here, peripheral blood inflammation-based biomarkers as well as previously less focused eosinophil fraction, modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) were systematically included to comprehensively analyze their potential in predicting neoadjuvant immunotherapy efficacy and prognosis. We enrolled 189 patients (94 in training and 95 in validation cohorts) with stage I-III B surgically resectable NSCLC treated with neoadjuvant immunotherapy from the National Cancer Center of China. Baseline and post-treatment eosinophils fraction, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte-to-lymphocyte ratio (MLR), PNI, mGPS, and their changes were calculated and analyzed for correlation with neoadjuvant immunotherapy efficacy and prognosis. In patients in the major pathological response (MPR) group, the post-treatment eosinophil fraction was significantly high, and NLR, PLR, SII, and MLR were significantly lower compared to the non-MPR group in both the training and validation cohorts. The receiver operating characteristic curve showed that post-treatment, eosinophil fraction and SII and their changing were two of the most important factors. Univariate and multivariate logistic regression analyses showed that post-treatment eosinophil fraction, SII, mGPS, and ΔSII could independently predict MPR in patients treated with neoadjuvant immunotherapy. Survival analysis showed a significant correlation between high post-treatment NLR, PLR, SII, mGPS, and their changes in ΔNLR and ΔSII elevation with poor overall survival and event-free survival of patients. Our results suggest that inflammatory biomarkers could predict the patient's response to neoadjuvant immunotherapy and prognosis.

BACKGROUND:Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC.METHODS:FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression.RESULTS:FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality.CONCLUSIONS:Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, disease burden became even severer in developing countries, especially for the population aged ≥40 years. Effective targeted preventive programs are strongly encouraged to reduce the FBC disease burden worldwide.

IntroductionA microsimulation model provides important references for decision-making regarding colorectal cancer (CRC) prevention strategies, yet such a well-validated model is scarce in China. MethodsWe comprehensively introduce the development of MIcrosimulation Model for the prevention and Intervention of Colorectal Cancer in China (MIMIC-CRC). The MIMIC-CRC was first constructed to simulate the natural history of CRC based on the adenoma-carcinoma pathway. The parameters were calibrated and validated using data from population-based cancer registry data and CRC screening programs. Furthermore, to assess the model's external validity, we compared the model-derived results to outcome patterns of a sigmoidoscopy screening trial in the UK [UK Flexible Sigmoidoscopy Screening (UKFSS) trial]. Finally, we evaluated the application potential of the MIMIC-CRC model in CRC screening by comparing the 8 different strategies. ResultsWe found that most of the model-predicted colorectal lesion prevalence was within the 95% CIs of observed prevalence in a large population-based CRC screening program in China. In addition, model-predicted sex- and age-specific CRC incidence and mortality were equivalent to the registry-based data. The hazard ratios of model-estimated CRC-related incidence and mortality for sigmoidoscopy screening compared to no screening were 0.60 and 0.51, respectively, which were comparable to the reported results of the UKFSS trial. Moreover, we found that all 8 strategies could reduce CRC incidence and mortality compared to no screening. ConclusionsThe well-calibrated and validated MIMIC-CRC model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies and will be useful for further decision-making to CRC prevention.

The influence of long-term diet on gut microbiota is an active area of investigation. The present work aimed to explore the associations between habitual diet patterns and gut microbiota in a large sample of asymptomatic Chinese adults. The gut microbiome was profiled through the sequencing of the 16S rRNA gene in stool samples from 702 Chinese adults aged 50–75 years who underwent colonoscopies and were diagnosed to be free of colorectal neoplasm. Long-term dietary consumption was assessed through a food-frequency questionnaire. The microbial associations with specific food groups and the posteriori dietary pattern were tested using the Kruskal–Wallis H test, permutational ANOVAs, and multivariate analyses with linear models. The Shannon indexes generally shared similar levels across different food intake frequency groups. Whole grain and vegetable intakes totally explained 1.46% of the microbiota compositional variance. Using the data-driven posteriori approach, a general dietary pattern characterized by lower intakes of refined grains was highlighted to be associated with higher abundances of the genus Anaerostipes and a species of it. We also observed 17 associations between various food group intakes and specific genera and species. For instance, the relative abundances of the genus Weissella and an uncultured species of it were negatively associated with red meat intake. The results of this study support the idea that the usual dietary consumption measured by certain food items or summary indexes is associated with gut microbial features. These results deepen the understanding of complex relationships of diet and gut microbiota, as well as their implications for gut microbiome studies of human chronic diseases.

The risk‐adapted screening strategy showed satisfying colorectal cancer (CRC) screening yield and efficiency. We therefore further explored the diagnostic performance variation of this strategy using different risk prediction models.

Background: An emerging increasing trend of pancreatic cancer (PC) incidence in young adults is reported in some countries. This study aims to describe the global trend of PC among young adults and to explore the related factors. Methods: Global and national data on PC incidence, disability-adjusted life-years, and attributive mortality were retrieved from the Global Burden of Disease 2019. The average annual percent change (AAPC) in incidence and mortality were estimated. Generalized additive models were applied to explore the non-linear associations between level, and change, of Human Development Index (HDI) and AAPC. Findings: Global PC incidence showed an increase during different periods from 1990 to 2019, especially in adults younger than 45 years old from 2010 to 2019, with an average increase rate of 0.69% per year (95% CI: 0.35 to 1.03). The AAPC of early-onset PC incidence during 2010–2019 was negatively correlated with HDI levels both in 2010 and 2019, while being positively correlated with HDI acceleration during that period. Significant increasing trends of early-onset PC incidence were observed over this period in 32 of 88 countries, mainly in South America, North America, Oceania, and Africa. Early-onset PC mortality attributed to high body mass index (BMI) and fasting plasma glucose (FPG) were increasing, while that attributed to tobacco use was declining. Interpretation: An emerging increasing trend has appeared in the global incidence and burden of early-onset PC over the last decades, which could be partly explained by the global epidemic of high BMI and FPG. Funding: CAMS Innovation Fund for Medical Sciences (CIFMS) 2021-I2M-1-002. Declaration of Interest: We declare no competing interests.

Breast cancer (BC) is the most prevalent malignancy worldwide, and a continued upward trend has been predicted in the coming decades. Screening in selected targeted populations, which is effective in reducing cancer-related mortality, has been widely implemented in many countries. This review summarizes the advances in BC screening techniques, organized or opportunistic BC screening programs across different countries, and screening modalities recommended by different academic authorities. Mammography is the most widely used and effective technique for BC screening. Other complementary techniques include ultrasound, clinical breast examination, and magnetic resonance imaging. Novel screening tests, including digital breast tomosynthesis and liquid biopsies, are still under development. Globally, the implementation status of BC screening programs is uneven, which is reflected by differences in screening modes, techniques, and population coverage. The recommended optimal screening strategies varied according to the authoritative guidelines. The effectiveness of current screening programs is influenced by several factors, including low detection rate, high false-positive rate, and unsatisfactory coverage and uptake rates. Exploration of accurate BC risk prediction models and the development of risk-stratified screening strategies are highly warranted in future research.

Hyperglycemia has been reported to increase the risk of pancreatic cancer (PC), while the association between glycemic change and PC risk has rarely been explored. Using data from a prospective cohort study conducted in China since 2006, 138,870 males with available fasting blood glucose (FBG) levels, including 106,632 males with at least two FBG measurements, were analyzed. The associations between FBG (level, change, and stability) and PC incidence were evaluated using Cox proportional hazard regression and restricted cubic splines. Baseline (p = 0.109) and recent (p = 0.070) FBG levels and incident PC were not significantly associated. U-shaped associations were observed between the annual FBG change and PC risk. Compared with stable FBG, participants with annual FBG change rates <−0.05 mmol/L or >0.15 mmol/L had about four-fold (HR, 4.010; 95% CI: 1.920−8.375) and six-fold (HR, 5.897; 95% CI: 2.935−11.848) higher PC risks, respectively. The PC risk increased by 2.5% (HRlinear = 1.025, 95% CI:1.009−1.042) for every 1% increase in the coefficient of variation for FBG. A subgroup analysis of males without diabetes at baseline showed stronger associations. Temporal FBG changes may be an important factor for identifying populations with high PC risks.

BACKGROUND:Globally, colorectal cancer (CRC) imposes a substantial burden on healthcare systems and confers considerable medical expenditures. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of CRC.METHODS:We used data from the GLOBOCAN database to estimate CRC incidence and mortality worldwide in 2020 and their association with the human development index (HDI). Trends of age-standardized rates of incidence and mortality in 60 countries (2000-2019) were evaluated by Joinpoint regression analysis using data of Global Burden of Disease 2019. The association between exposure to country-level lifestyle, metabolic and socioeconomic factors obtained from the World Health Organization Global Health Observatory and World Bank DataBank data and CRC incidence and mortality was determined by multivariable linear regression.RESULTS:CRC incidence and mortality varied greatly in the 60 selected countries, and much higher incidence and mortality were observed in countries with higher HDIs, and vice versa. From 2000 to 2019, significant increases of incidence and mortality were observed for 33 countries (average annual percent changes [AAPCs], 0.24-3.82) and 18 countries (AAPCs, 0.41-2.22), respectively. A stronger increase in incidence was observed among males (AAPCs, 0.36-4.54) and individuals <50 years (AAPCs, 0.56-3.86). Notably, 15 countries showed significant decreases in both incidence (AAPCs, -0.24 to -2.19) and mortality (AAPCs, -0.84 to -2.74). A significant increase of incidence among individuals <50 years was observed in 30 countries (AAPCs, 0.28-3.62). Countries with higher incidence were more likely to have a higher prevalence of alcohol drinking, higher level of cholesterol level, higher level of unemployment, and a poorer healthcare system.CONCLUSIONS:Some high-HDI countries showed decreasing trends in CRC incidence and mortality, whereas developing countries that previously had low disease burden showed significantly increased incidence and mortality trends, especially in males and populations ≥50 years, which require targeted preventive health programs.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. China, Europe and northern America account for more than half of the new CRC cases and associated deaths globally. This review summarizes the current status and temporal trends of CRC in China, Europe, and northern America. The potential primary preventive strategies and latest advances in CRC screening techniques and programs are discussed. Recently, the incidence and mortality of CRC in some European and northern American countries have decreased; conversely, CRC incidence and mortality continue to increase in China. The overall 5-year relative survival rate for CRC is similar between these regions, but there is considerable heterogeneity among European countries. Implementing population-based CRC screening programs can effectively address the growing disease burden. The effectiveness of nationwide CRC screening programs in these regions has been limited by relatively low coverage and participation rate. The deployment of state-of-the-art techniques and precise risk-adapted screening strategies incorporating effective risk prediction models and screening techniques may boost screening effectiveness. Our review provides novel foundations for the development and optimization of CRC preventive strategies.