Background There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels.This study aimed to assess the association of ...Background There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels.This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels.Methods This study utilized individual participant data from 21 cohort studies,comprising both published and unpublished data.Eligibility criteria included individual-level data on leisure-time and occupational physical activity(categorized as sedentary,low,moderate,and high)along with data on all-cause and/or cardiovascular mortality.A 2-stage individual participant data meta-analysis was conducted,with separate analysis of each study using Cox proportional hazards models(Stage 1).These results were combined using random-effects models(Stage 2).Results Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels,for both males and females.Among males with sedentary work,high compared to sedentary leisure-time physical activity was associated with lower all-cause(hazard ratios(HR)=0.77,95%confidence interval(95%CI):0.70-0.85)and cardiovascular mortality(HR=0.76,95%CI:0.66-0.87)risk.Among males with high levels of occupational physical activity,high compared to sedentary leisure-time physical activity was associated with lower all-cause(HR=0.84,95%CI:0.74-0.97)and cardiovascular mortality(HR=0.79,95%CI:0.60-1.04)risk,while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant.Among females,most effects were similar but more imprecise,especially in the higher occupational physical activity levels.Conclusion Higher levels of leisure-time physical activity were generally associated with lower mortality risks.However,results for workers with moderate and high occupational physical activity levels,especially women,were more imprecise.Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity,irrespective of their level of occupational physical activity.展开更多
Functional dyspepsia （FD） is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mech...Functional dyspepsia （FD） is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mechanisms, the underlying casual pathways associated with FD remain obscure. The currently proposed pathophysiologic mechanisms associated with FD include genetic susceptibility, delayed as well as accelerated gastric emptying, visceral hypersensitivity to acid or mechanical distention, impaired gastric accommodation, abnormal fundic phasic contractions, abnormal antroduodenal motility, acute and chronic infections, and psychosocial comorbidity. A greater understanding of the abnormalities underlying FD may lead to improved management. The aim of this editorial is to provide a critical overview of current pathophysiologic concepts in functional dyspepsia.展开更多
AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic,...AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.展开更多
Helicobacter pylori(H. pylori) infection is a wellestablished risk factor for the development of gastric cancer(GC), one of the most common and deadliest neoplasms worldwide. H. pylori infection induces chronic inflam...Helicobacter pylori(H. pylori) infection is a wellestablished risk factor for the development of gastric cancer(GC), one of the most common and deadliest neoplasms worldwide. H. pylori infection induces chronic inflammation in the gastric mucosa that, in the absence of treatment, may progress through a series of steps to GC. GC is only one of several clinical outcomes associated with this bacterial infection, which may be at least partially attributed to the high genetic variability of H. pylori. The biological mechanisms underlying how and under what circumstances H. pylori alters normal physiological processes remain enigmatic. A key aspect of carcinogenesis is the acquisition of traits that equip preneoplastic cells with the ability to invade. Accumulating evidence implicates H. pylori in the manipulation of cellular and molecular programs that are crucial for conferring cells with invasive capabilities. We present here an overview of the main findings about the involvement of H. pylori in the acquisition of cell invasive behavior, specifically focusing on the epithelial-to-mesenchymal transition, changes in cell polarity, and deregulation of molecules that control extracellular matrix remodeling.展开更多
Background & Aims: The epidemiology of fecal incontinence (FI) is incompletely understood. We report the pre- valence, clinical spectrum, health care- seeking behavior, and quality of life (QOL) in community women...Background & Aims: The epidemiology of fecal incontinence (FI) is incompletely understood. We report the pre- valence, clinical spectrum, health care- seeking behavior, and quality of life (QOL) in community women with FI. Methods: A questionnaire was mailed to an age- stratified random sample of 5300 Olmsted County, Minnesota, women identified by the Rochester Epidemiology Project. Symptom severity was assessed by a validated scale, and impact on QOL was evaluated for subjects who had any FI during the past year. The prevalence of FI was calculated with direct age adjustment to the 2000 US white female population. Results: Altogether, 2800 of 5300 women (53% ) responded to the survey. The overall age- adjusted prevalence of FI in the past year was 12.1 per 100 (95% confidence interval, 11.0- 13.1). The prevalence increased with age from 7 (third decade) to 22 (sixth decade) per 100 and was steady thereafter. Symptoms were mild (45% ), moderate (50% ), or severe (5% ), and symptom severity was related to the impact of FI on QOL and physician- consulting behavior. Moderate to severe impact on < 1 domain of QOL was reported by 6% with mild, 35% with moderate, and 82% with severe symptoms, whereas 5% with mild, 10% with moderate, and 48% with severe FI had consulted a physician for FI in the past year. Conclusions: More than 1 of 10 adult women in the population have FI; almost 1 of 15 have moderate to severe FI. FI significantly impacts QOL and prompts health care utilization predominantly in women with moderate to severe symptoms.展开更多
Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechani...Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechanisms such as insulin resistance or inflammation may not only predispose individuals withCMDto an elevated risk of certain types of cancer but also to a diagnosis of cancer at an advanced stage[1,2].展开更多
Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regardin...Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited.Thus,we investigated the associations between dietary intake by degree of food processing and breast cancer risk,overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition(EPIC)study.Dietary intake of EPIC participants was assessed via questionnaires at baseline.More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system:unprocessed/minimally processed(NOVA 1),culinary ingredients(NOVA 2),processed(NOVA 3)and ultra-processed(NOVA 4).Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)of breast cancer per standard deviation increase in daily consumption(grams)of foods from each NOVA group.The current analysis included 14,933 breast cancer cases,diagnosed among the 318,686 EPIC female participants,(median follow-up of 14.9 years).No associations were found between breast cancer risk and the level of dietary intake from NOVA 1[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)],NOVA 2[HR_(per 1 SD)=1.01(95%CI 0.98-1.03)]and NOVA 4[HR_(per 1 SD)=1.01(95%CI 0.99-1.03)]foods.However,a positive association was found between NOVA 3 and breast cancer risk[HR_(per 1 SD)=1.05(95%CI 1.03-1.07)]which became non-significant after adjustment for alcohol intake[HR_(per 1 SD)=1.01(95%CI 0.98-1.05)]or when beer and wine were excluded from this group[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)].The associations did not differ by breast cancer subtype,menopausal status or body mass index.Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption.展开更多
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integr...Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.展开更多
Dear Editor,In the European region,which shares 22.8%of the global cancer burden for 10%of the global population,there were around 4.4 million new cancer cases and 1.9 million deaths from cancer in 2020[1].The reasons...Dear Editor,In the European region,which shares 22.8%of the global cancer burden for 10%of the global population,there were around 4.4 million new cancer cases and 1.9 million deaths from cancer in 2020[1].The reasons for the high cancer incidence rates are complex;however,diet and dietary components are among the main contributors to cancer risk[2].In modern-day living,a growing proportion of people include in their diets ultra-processed foods.Byproducts of food processing and home-prepared foods are so-called dietary advanced glycation endproducts(AGEs),which are reactive metabolites emerging during the breakdown of reducing sugar.AGEs production is preponderant in dry high-heat processes(e.g.,baking,roasting);hence foods such as cakes,crisps,crackers,cereal products,meat and meat-derived products represent a major source of dietary AGEs[3].展开更多
基金The Trùndelag Health Study (HUNT) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology), Trùndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public HealthThe coordination of European Prospective Investigation into Cancer and Nutrition - Spain study (EPIC) is financially supported by the International Agency for Research on Cancer (IARC)+7 种基金by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)supported by Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc 1a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain)funded by The Netherlands Organisation for Health Research and DevelopmentZon Mw (Grant No.: 531-00141-3)Funding for the SHIP study has been provided by the Federal Ministry for Education and Research (BMBFidentification codes 01 ZZ96030, 01 ZZ0103, and 01 ZZ0701)support from the Swedish Research Council (2018-02527 and 2019-00193)financed by the Helmholtz Zentrum München - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria.
文摘Background There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels.This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels.Methods This study utilized individual participant data from 21 cohort studies,comprising both published and unpublished data.Eligibility criteria included individual-level data on leisure-time and occupational physical activity(categorized as sedentary,low,moderate,and high)along with data on all-cause and/or cardiovascular mortality.A 2-stage individual participant data meta-analysis was conducted,with separate analysis of each study using Cox proportional hazards models(Stage 1).These results were combined using random-effects models(Stage 2).Results Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels,for both males and females.Among males with sedentary work,high compared to sedentary leisure-time physical activity was associated with lower all-cause(hazard ratios(HR)=0.77,95%confidence interval(95%CI):0.70-0.85)and cardiovascular mortality(HR=0.76,95%CI:0.66-0.87)risk.Among males with high levels of occupational physical activity,high compared to sedentary leisure-time physical activity was associated with lower all-cause(HR=0.84,95%CI:0.74-0.97)and cardiovascular mortality(HR=0.79,95%CI:0.60-1.04)risk,while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant.Among females,most effects were similar but more imprecise,especially in the higher occupational physical activity levels.Conclusion Higher levels of leisure-time physical activity were generally associated with lower mortality risks.However,results for workers with moderate and high occupational physical activity levels,especially women,were more imprecise.Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity,irrespective of their level of occupational physical activity.
文摘Functional dyspepsia （FD） is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mechanisms, the underlying casual pathways associated with FD remain obscure. The currently proposed pathophysiologic mechanisms associated with FD include genetic susceptibility, delayed as well as accelerated gastric emptying, visceral hypersensitivity to acid or mechanical distention, impaired gastric accommodation, abnormal fundic phasic contractions, abnormal antroduodenal motility, acute and chronic infections, and psychosocial comorbidity. A greater understanding of the abnormalities underlying FD may lead to improved management. The aim of this editorial is to provide a critical overview of current pathophysiologic concepts in functional dyspepsia.
基金Supported by The American Society of Preventive Oncology/Prevent Cancer Foundation/American Society for Clinical Oncology Cancer Prevention Research Fellowship to SVAthe Australasian Colorectal Cancer Family Registry, No. U01CA097735+5 种基金the Familial Colorectal Neoplasia Collaborative Group, No. U01 CA074799the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies, No. U01 CA074800the Ontario Registry for Studies of Familial Colorectal Cancer, No.U01 CA074783the Seattle Colorectal Cancer Family Registry,No. U01 CA074794the University of Hawaii Colorectal Cancer Family Registry, No. U01 CA074806the University of California, Irvine Informatics Center, No. U01 CA078296
文摘AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.
基金Supported by Vicerrectoría de Investigación of the University of Costa Rica,No.B6A11,No.B7281 and No.90912
文摘Helicobacter pylori(H. pylori) infection is a wellestablished risk factor for the development of gastric cancer(GC), one of the most common and deadliest neoplasms worldwide. H. pylori infection induces chronic inflammation in the gastric mucosa that, in the absence of treatment, may progress through a series of steps to GC. GC is only one of several clinical outcomes associated with this bacterial infection, which may be at least partially attributed to the high genetic variability of H. pylori. The biological mechanisms underlying how and under what circumstances H. pylori alters normal physiological processes remain enigmatic. A key aspect of carcinogenesis is the acquisition of traits that equip preneoplastic cells with the ability to invade. Accumulating evidence implicates H. pylori in the manipulation of cellular and molecular programs that are crucial for conferring cells with invasive capabilities. We present here an overview of the main findings about the involvement of H. pylori in the acquisition of cell invasive behavior, specifically focusing on the epithelial-to-mesenchymal transition, changes in cell polarity, and deregulation of molecules that control extracellular matrix remodeling.
文摘Background & Aims: The epidemiology of fecal incontinence (FI) is incompletely understood. We report the pre- valence, clinical spectrum, health care- seeking behavior, and quality of life (QOL) in community women with FI. Methods: A questionnaire was mailed to an age- stratified random sample of 5300 Olmsted County, Minnesota, women identified by the Rochester Epidemiology Project. Symptom severity was assessed by a validated scale, and impact on QOL was evaluated for subjects who had any FI during the past year. The prevalence of FI was calculated with direct age adjustment to the 2000 US white female population. Results: Altogether, 2800 of 5300 women (53% ) responded to the survey. The overall age- adjusted prevalence of FI in the past year was 12.1 per 100 (95% confidence interval, 11.0- 13.1). The prevalence increased with age from 7 (third decade) to 22 (sixth decade) per 100 and was steady thereafter. Symptoms were mild (45% ), moderate (50% ), or severe (5% ), and symptom severity was related to the impact of FI on QOL and physician- consulting behavior. Moderate to severe impact on < 1 domain of QOL was reported by 6% with mild, 35% with moderate, and 82% with severe symptoms, whereas 5% with mild, 10% with moderate, and 48% with severe FI had consulted a physician for FI in the past year. Conclusions: More than 1 of 10 adult women in the population have FI; almost 1 of 15 have moderate to severe FI. FI significantly impacts QOL and prompts health care utilization predominantly in women with moderate to severe symptoms.
基金funded by the French National Cancer Institute(INCA_N◦2018-123)and supported by Canccrole Ile-de-France(N◦2018-1-PL SHS-06-CIRC-1)supported by the International Agency for Research on Cancer(IARC)and also by the Department of Epidemiology and Biostatistics,School of Public Health,Imperial College London,which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre(BRC)+9 种基金supported by:Danish Cancer Society(Denmark)Ligue Contre le Cancer,Institut Gustave Roussy,Mutuelle Générale de l’Education Nationale,Institut National de la Santéet de la Recherche Médicale(INSERM)(France)German Cancer Aid,German Cancer Research Center(DKFZ),German Institute of Human Nutrition Potsdam-Rehbruecke(DIfE),Federal Ministry of Education and Research(BMBF)(Germany)Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy,Compagnia di SanPaolo and National Research Council(Italy)Dutch Ministry of Public Health,Welfare and Sports(VWS),Netherlands Cancer Registry(NKR),LK Research Funds,Dutch Prevention Funds,Dutch ZON(Zorg Onderzoek Nederland),World Cancer Research Fund(WCRF),Statistics Netherlands(The Netherlands)Health Research Fund(FIS)-Instituto de Salud Carlos III(ISCIII),Regional Governments ofAndalucía,Asturias,Basque Country,Murcia and Navarra,and the Catalan Institute of Oncology-ICO(Spain)Swedish Cancer Society,Swedish Research Council and County Councils of Skane and Vasterbotten(Sweden)Cancer Research UK(14136 to EPIC-NorfolkC8221/A29017 to EPIC-Oxford),Medical Research Council(1000143 to EPIC-NorfolkMR/M012190/1 to EPIC-Oxford)(United Kingdom).
文摘Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechanisms such as insulin resistance or inflammation may not only predispose individuals withCMDto an elevated risk of certain types of cancer but also to a diagnosis of cancer at an advanced stage[1,2].
基金supported by a Wellcome Trust PhD studentship in Molecular,Genetic and Lifecourse Epidemiology(224982/Z/22/Z).
文摘Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited.Thus,we investigated the associations between dietary intake by degree of food processing and breast cancer risk,overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition(EPIC)study.Dietary intake of EPIC participants was assessed via questionnaires at baseline.More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system:unprocessed/minimally processed(NOVA 1),culinary ingredients(NOVA 2),processed(NOVA 3)and ultra-processed(NOVA 4).Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)of breast cancer per standard deviation increase in daily consumption(grams)of foods from each NOVA group.The current analysis included 14,933 breast cancer cases,diagnosed among the 318,686 EPIC female participants,(median follow-up of 14.9 years).No associations were found between breast cancer risk and the level of dietary intake from NOVA 1[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)],NOVA 2[HR_(per 1 SD)=1.01(95%CI 0.98-1.03)]and NOVA 4[HR_(per 1 SD)=1.01(95%CI 0.99-1.03)]foods.However,a positive association was found between NOVA 3 and breast cancer risk[HR_(per 1 SD)=1.05(95%CI 1.03-1.07)]which became non-significant after adjustment for alcohol intake[HR_(per 1 SD)=1.01(95%CI 0.98-1.05)]or when beer and wine were excluded from this group[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)].The associations did not differ by breast cancer subtype,menopausal status or body mass index.Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption.
基金the Key International(Regional)Cooperative Research Project(No.81820108028)the National Natural Science Foundation of China(Nos.81521004,81922061,81973123,and 81803306)+2 种基金the Science Foundation for Distinguished Young Scholars of Jiangsu(No.BK20160046)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).the National Cancer Institute,National Institutes of Health of USA through grants U01-CA063673,UM1-CA167462,and U01-CA167462.
文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
基金the Fondation de France(FDF,grant no.00081166,HF and RC,and FDF grant no.00089811,ALM)the Wereld Kanker Onderzoek Fonds(WKOF),as part of the World Cancer Research Fund(WCRF)International grant programme(WCRF 2015-1391,PI Dr.Mazda Jenab,International Agency for Research on Cancer)。
文摘Dear Editor,In the European region,which shares 22.8%of the global cancer burden for 10%of the global population,there were around 4.4 million new cancer cases and 1.9 million deaths from cancer in 2020[1].The reasons for the high cancer incidence rates are complex;however,diet and dietary components are among the main contributors to cancer risk[2].In modern-day living,a growing proportion of people include in their diets ultra-processed foods.Byproducts of food processing and home-prepared foods are so-called dietary advanced glycation endproducts(AGEs),which are reactive metabolites emerging during the breakdown of reducing sugar.AGEs production is preponderant in dry high-heat processes(e.g.,baking,roasting);hence foods such as cakes,crisps,crackers,cereal products,meat and meat-derived products represent a major source of dietary AGEs[3].
