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- He, YQ, et al.
(författare)
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A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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- Li, MY, et al.
(författare)
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Ncf1 Governs Immune Niches in the Lung to Mediate Pulmonary Inflammation in Mice
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 783944-
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil cytosolic factor 1 (Ncf1) is a major genetic factor associated with autoimmune diseases and has been identified as a key player in autoimmune mediated inflammation. We addressed the role ofNcf1in an antigen-induced pulmonary inflammation model, and found that theNcf1m1jmutation, causing a deficient reactive oxygen species response, alleviated disease. TheNcf1m1jmutation was associated with a reduced inflammatory cell infiltration in airways, but had limited effect on mucus secretion, antibody production and lung fibrosis. The disease remission in theNcf1mutated mice was reversed when functionalNcf1was transgenically expressed in alveolar macrophages, suggesting that the cellular inflammation was depended on functionalNcf1in alveolar macrophages. By determining cytokine and chemokine profiles in lung and serum, we found thatNcf1deficiency allowed an increased expression of Th1 cytokines, including TNF-α, IFN-γ and IL-12. Since also epithelial cytokines were found to be regulated byNcf1, we tested the effect ofNcf1in IL-33 and IL-25 induced lung inflammation models. Mice with theNcf1m1jmutation showed less sensitivity to IL-33, but not IL-25, induced lung inflammation, in a macrophage independent manner. The mice with deficientNcf1showed a reduced eosinophil infiltration and group 2 innate lymphoid cell (ILC2) activation. The production of IFN-γ in CD4+T cells was increased, whereas IL-5 and IL-13 in ILC2 were decreased. Importantly, anti-IFN-γ antibody treatment ofNcf1deficient mice increased eosinophil infiltration and rescued ILC2 activation in the lung. We conclude thatNcf1deficiency enhances Th1 response, deactivates ILC2, and protects against pulmonitis.
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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- Mao, W, et al.
(författare)
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Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial
- 2021
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Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11, s. 627185-
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Tidskriftsartikel (refereegranskat)abstract
- Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects.Clinical Trial Registration:http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.
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- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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- Wei, X, et al.
(författare)
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Protocol of an iterative qualitative study to develop a molecular testing decision aid for shared decision-making in patients with lung cancer after surgery
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e061367-
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Tidskriftsartikel (refereegranskat)abstract
- Although molecular testing is crucial for many patients with lung cancer, the decision to carry out molecular testing is not easy to make in actual clinical scenarios. Using a specific decision aid (DA) to conduct shared decision-making (SDM) may help ameliorate this problem. However, no DA currently exists for lung cancer molecular testing (DA_LCMT). We aim to develop an evidence-based, iteratively refined DA, which may facilitate SDM and improve the quality of SDM.Methods and analysisAfter considering the Ottawa Decision Support Framework, International Patient Decision Aid Standards and Food and Drug Administration guidance about methods to identify what is important to patients, semistructured interviews with qualitative research methods will be used to generate the decision-making needs of patients with lung cancer diagnosed with lung adenocarcinoma by intraoperative frozen pathological sections. Input will be provided by patients and other stakeholders, including thoracic surgeons, nurses, hospital administrators, molecular testing company staff and insurance company staff. Then, a modified Delphi method will be used to develop the DA_LCMT V.1.0 (DA_LCMT 1.0). Structured interviews with qualitative research methods will be used in the cognitive debriefing (alpha tests) and field testing (beta tests) to revise and improve the DA_LCMT from version 1.0 to the final version, version 3.0. Descriptive statistics will be used to summarise the baseline characteristics of the patients and other stakeholders. Qualitative data will be analysed using the three steps of grounded theory: generate a codebook, update the codebook and create a comprehensive list of related items.Ethics and disseminationEthics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study. This protocol is based on the latest version 1.0, dated 31 October 2021. The study was also approved by the Ethics Committees of The Third People’s Hospital of Chengdu, Zigong First People’s Hospital and Jiangyou People’s Hospital. The results of this study will be presented at medical conferences and published in peer-reviewed journals.Trial registration numberNCT05191485.
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- Zhou, X, et al.
(författare)
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Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study
- 2022
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 37:7, s. 701-712
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol intake is thought to be a risk factor for breast cancer, but the causal relationship and carcinogenic mechanisms are not clear. We performed an up-to-date meta-analysis of prospective studies to assess observational association, and then conducted MR analysis to make causal inference based on the genetic predisposition to alcohol consumption (“drinks per week”) and pathological drinking behaviours (“alcohol use disorder” and “problematic alcohol use”), as well as genetically predicted DNA methylation at by alcohol-related CpG sites in blood. We found an observational dose–response association between alcohol intake and breast cancer incidence with an additional risk of 4% for per 10 g/day increase in alcohol consumption. Genetic predisposition to alcohol consumption (“drinks per week”) was not causally associated with breast cancer incidence at the OR of 1.01 (95% CI 0.84, 1.23), but problematic alcohol use (PAU) was linked to a higher breast cancer risk at the OR of 1.76 (95% CI 1.04, 2.99) when conditioning on alcohol consumption. Epigenetic MR analysis identified four CpG sites, cg03260624 near CDC7 gene, cg10816169 near ZNF318 gene, cg03345232 near RIN3 gene, and cg26312998 near RP11-867G23.13 gene, where genetically predicted epigenetic modifications were associated with an increased breast cancer incidence risk. Our findings re-affirmed that alcohol consumption is of high risk for breast cancer incidence even at a very low dose, and the pathogenic effect of alcohol on breast cancer could be due to pathological drinking behaviour and epigenetic modification at several CpG sites, which could be potential intervention targets for breast cancer prevention.
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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Huang, JJ, et al.
(författare)
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Cancer Incidence and Mortality in Asian Countries: A Trend Analysis
- 2022
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Ingår i: Cancer control : journal of the Moffitt Cancer Center. - : SAGE Publications. - 1526-2359. ; 29, s. 10732748221095955-
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to evaluate the updated burden and temporal trends of cancer incidence and mortality in Asian countries. Methodology The data used in this study were retrieved from the Global Cancer Observatory, Cancer Incidence in Five Continents volumes I-XI, and the World Health Organization mortality database. These data were used to calculate the Average Annual Percentage Change (AAPC), with a 95% confidence interval (CI) by joinpoint regression analysis to determine the epidemiological trend in the past decade. Results In 2020, the cancer incidence in Asia was 169.1 per 1 00 000, accounting for 49.3% of the global cancer incidence. The most common cancers included lung (13.8%), breast (10.8%) and colorectal (10.6%) cancers. Its mortality was 101.6 per 1 00 000 (58.3% of the global cancer death) with lung (19.2%), liver (10.5%) and stomach (9.9%) cancers being the most common causes of cancer death. The cancer incidence had been increasing in female population, with Korea (AAPC = 5.73, 95% CI [5.30, 6.17], P < .001), Japan (AAPC = 2.67, 95% CI [2.12, 3.23], P < .001) and Kuwait (AAPC = 2.08, 95% CI [.49, 3.69], P = .016) showing the most significant increases in the past decade. The incidence increase was also observed among population aged <40 years old, with Korea (female AAPC = 8.42, 95% CI [7.40, 9.45], P < .001; male AAPC = 5.28, 95% CI [4.23, 6.33], P <.001), China (female AAPC = 2.94, 95% CI [2.07, 3.81], P < .001; male AAPC = 1.37, 95% CI [.57, 2.18], P = .004) and Japan (female AAPC = 2.88, 95% CI [1.88, 3.88], P = .016; male AAPC = 1.59, 95% CI [.40, 2.78], P = .015) showing the most significant increases. However, there was an overall decreasing trend of cancer mortality. Conclusions There was a substantial burden of cancer incidence and mortality in Asia. Although there was a decreasing trend in cancer mortality, its incidence had been increasing especially among female and younger populations. Future studies could be done to further investigate the potential reasons for these epidemiologic trends.
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- Huang, JJ, et al.
(författare)
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Disease Burden, Risk Factors, and Recent Trends of Liver Cancer: A Global Country-Level Analysis
- 2021
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Ingår i: Liver cancer. - : S. Karger AG. - 2235-1795 .- 1664-5553. ; 10:4, s. 330-345
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> This study aimed to evaluate the updated disease burden, risk factors, and temporal trends of liver cancer based on age, sex, and country. <b><i>Methods:</i></b> We estimated the incidence of liver cancer and its attribution to hepatitis B virus (HBV) and hepatitis C virus (HCV) in 2018 based on the Global Cancer Observatory and World Health Organization (WHO) Cancer Causes database<i>.</i> We extracted the prevalence of risk factors from the WHO Global Health Observatory to examine the associations by weighted linear regression. The trend analysis used data from the <i>Cancer Incidence in Five Continents</i> and the WHO mortality database from 48 countries. Temporal patterns of incidence and mortality were calculated using average annual percent change (AAPC) by joinpoint regression analysis. <b><i>Results:</i></b> The global incidence of liver cancer was (age-standardized rate [ASR]) 9.3 per 100,000 population in 2018, and there was an evident disparity in the incidence related to HBV (ASR 0.2–41.2) and HCV (ASR 0.4–43.5). A higher HCV/HBV-related incidence ratio was associated with a higher level of alcohol consumption (β 0.49), overweight (β 0.51), obesity (β 0.64), elevated cholesterol (β 0.70), gross domestic product (β 0.20), and Human Development Index (HDI; β 0.45). An increasing trend in incidence was identified in many countries, especially for male individuals, population aged ≥50 years, and countries with a higher HCV/HBV-related liver cancer incidence ratio. Countries with the most drastic increase in male incidence were reported in India (AAPC 7.70), Ireland (AAPC 5.60), Sweden (AAPC 5.72), the UK (AAPC 5.59), and Norway (AAPC 4.87). <b><i>Conclusion:</i></b> We observed an overall increasing trend of liver cancer, especially among male subjects, older individuals, and countries with a higher prevalence of HCV-related liver cancer. More efforts are needed in enhancing lifestyle modifications and accessibility of antiviral treatment for these populations. Future studies should investigate the reasons behind these epidemiological changes.
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- Huang, JJ, et al.
(författare)
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Disease Burden, Risk Factors, and Trends of Leukaemia: A Global Analysis
- 2022
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 904292-
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Tidskriftsartikel (refereegranskat)abstract
- Leukaemia accounted for approximately 2.5% of all new cancer incidence and 3.1% of cancer-related mortality. The investigation of its risk factors and epidemiologic trends could help describe the geographical distribution and identify high-risk population groups. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of leukaemia by sex, age, and country. We extracted incidence and mortality of leukaemia from GLOBOCAN, CI5, WHO mortality database, NORDCAN, and SEER. We searched the WHO Global Health Observatory data repository for the age-standardised prevalence of lifestyle and metabolic risk factors. We tested the trends by calculating Average Annual Percentage Change (AAPC) from Joinpoint regression. The age-standardized rate of incidence and mortality were 5.4 and 3.3 per 100,000 globally. The incidence and mortality of leukaemia were associated with Human Development Index, Gross Domestics Products per capita, prevalence of smoking, physical activity, overweight, obesity, and hypercholesterolaemia at the country level. Overall, more countries were showing decreasing trends than increasing trends in incidence and mortality. However, an increasing trend of leukaemia incidence was found in Germany, Korea, Japan, Canada and the United Kingdom (AAPC, 2.32-0.98) while its mortality increased in the Philippines, Ecuador, Belarus, and Thailand (AAPC, 2.49-1.23). There was a decreasing trend of leukaemia for the past decade while an increase in incidence and mortality was observed in some populations. More intensive lifestyle modifications should be implemented to control the increasing trends of leukaemia in regions with these trends. Future studies may explore the reasons behind these epidemiological transitions.
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- Huang, JJ, et al.
(författare)
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Global Burden, Risk Factors, and Trends of Esophageal Cancer: An Analysis of Cancer Registries from 48 Countries
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to examine the global burden, risk factors, and trends of esophageal cancer based on age, sex, and histological subtype. The data were retrieved from cancer registries database from 48 countries in the period 1980–2017. Temporal patterns of incidence and mortality were evaluated by average annual percent change (AAPC) using joinpoint regression. Associations with risk factors were examined by linear regression. The highest incidence of esophageal cancer was observed in Eastern Asia. The highest incidence of adenocarcinoma (AC) was found in the Netherlands, the United Kingdom, and Ireland. A higher AC/squamous cell carcinoma (SCC) incidence ratio was associated with a higher prevalence of obesity and elevated cholesterol. We observed an incidence increase (including AC and SCC) in some countries, with the Czech Republic (female: AAPC 4.66), Spain (female: 3.41), Norway (male: 3.10), Japan (female: 2.18), Thailand (male: 2.17), the Netherlands (male: 2.11; female: 1.88), and Canada (male: 1.51) showing the most significant increase. Countries with increasing mortality included Thailand (male: 5.24), Austria (female: 3.67), Latvia (male: 2.33), and Portugal (male: 1.12). Although the incidence of esophageal cancer showed an overall decreasing trend, an increasing trend was observed in some countries with high AC/SCC incidence ratios. More preventive measures are needed for these countries.
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