{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:44:54Z","timestamp":1790912694763,"version":"4.1.0"},"reference-count":51,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"\n Importance<\/jats:title>\n Identifying individuals at higher risk of pancreatic cancer (PC) is critical for developing targeted prevention strategies.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate whether the potential association of modifiable risk factors with PC varies across genetic risk profiles and age.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This prospective population-based cohort study used data from participants in the UK Biobank, enrolled from 2006 to 2010 and followed up for a median (IQR) of 11.7 (10.9-12.9) years. Data analysis was conducted from January to September 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n A polygenic risk score (PRS) and a modifiable risk score (MRS; including smoking, excessive alcohol intake, unhealthy diet, physical inactivity, overweight, diabetes, and pancreatitis) for PC were each categorized as low, intermediate, and high.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The main outcome, incident PC, was ascertained through record linkage with national registries. Hazard ratios (HRs) were estimated to assess the individual and joint associations of the MRS and PRS with PC across age groups (&amp;lt;60, 60-69, and \u226570 years). Standardized 10-year cumulative incidence (SCI) per 100\u202f000 persons was calculated according to MRS and PRS strata across age groups.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 290\u202f645 participants (149\u202f836 [51.6%] male; mean [SD] age, 56.1 [8.1] years) were included. During follow-up, 1187 participants (0.41%) developed incident PC. The PRS was consistently associated with increased PC risk across all age groups (HR per 1-SD increase in PRS: age &amp;lt;60 years, 1.39; 95% CI, 1.15-1.68; age 60-69 years, 1.66; 95% CI, 1.51-1.83; age \u226570 years, 1.37; 95% CI, 1.26-1.48;\n P<\/jats:italic>\n for interaction\u2009=\u2009.43), while MRS showed stronger associations with PC in younger than older participants (HR per 1-point increase in MRS: age &amp;lt;60 years, 1.69; 95% CI, 1.43-2.01; age 60-69 years, 1.25; 95% CI, 1.14-1.36; age \u226570 years, 1.20; 95% CI, 1.12-1.29;\n P<\/jats:italic>\n for interaction\u2009&amp;lt;\u2009.001). SCIs varied across combinations of PRS and MRS strata, and were higher with increasing MRS in all PRS groups. Among participants younger than 60 years, individuals with high PRS but low MRS had a lower SCI (38.2 events per 100\u202f000 persons) than those with low PRS but high MRS (92.2 events per 100\u202f000 persons). The absolute difference in SCIs between high and low MRS groups was greatest among individuals with high PRS, being 6.1-fold greater than that observed among those at low PRS (323.1 vs 52.8 per 100\u202f000 persons). The corresponding fold differences were less pronounced in individuals aged 60 to 69 years and 70 years or older (1.2- and 2.8-fold; 500.1 vs 401.2 per 100\u202f000 persons and 851.2 vs 304.9 per 100\u202f000 persons, respectively).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study found that the associations of modifiable risk factors with PC were strongest among younger adults, especially those at high genetic risk. These findings highlight the importance of initiating prevention early in the life course, especially among individuals at high genetic risk.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.1192","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:32:24Z","timestamp":1778772744000},"page":"714","source":"Crossref","is-referenced-by-count":1,"title":["Age-Dependent Interplay of Modifiable Risk Factors and Genetic Risk in Pancreatic Cancer"],"prefix":"10.1001","volume":"12","author":[{"given":"Jie","family":"Ding","sequence":"first","affiliation":[{"name":"Division of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Heidelberg, Germany"},{"name":"Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Edelmann","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid V.","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Heidelberg, Germany"},{"name":"Department of Translational Medicine, Division of Urological Cancers, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Sch\u00f6ttker","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"Cancer Prevention Graduate School, German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hoffmeister","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"10242","key":"coi260019r1","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1016\/S0140-6736(20)30974-0","article-title":"Pancreatic cancer.","volume":"395","author":"Mizrahi","year":"2020","journal-title":"Lancet"},{"issue":"4","key":"coi260019r2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.4708","article-title":"Estimated projection of US cancer incidence and death to 2040.","volume":"4","author":"Rahib","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"3","key":"coi260019r4","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1053\/j.gastro.2020.10.007","article-title":"Worldwide burden of, risk factors for, and trends in pancreatic cancer.","volume":"160","author":"Huang","year":"2021","journal-title":"Gastroenterology"},{"issue":"3","key":"coi260019r5","doi-asserted-by":"publisher","first-page":"e137","DOI":"10.1016\/S2468-2667(18)30267-6","article-title":"Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry.","volume":"4","author":"Sung","year":"2019","journal-title":"Lancet Public Health"},{"issue":"7","key":"coi260019r6","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41575-021-00457-x","article-title":"Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors.","volume":"18","author":"Klein","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"7","key":"coi260019r7","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1093\/annonc\/mdr541","article-title":"Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).","volume":"23","author":"Bosetti","year":"2012","journal-title":"Ann Oncol"},{"issue":"2","key":"coi260019r8","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1093\/annonc\/mdr120","article-title":"Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).","volume":"23","author":"Lucenteforte","year":"2012","journal-title":"Ann Oncol"},{"issue":"8","key":"coi260019r9","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1001\/jama.286.8.921","article-title":"Physical activity, obesity, height, and the risk of pancreatic cancer.","volume":"286","author":"Michaud","year":"2001","journal-title":"JAMA"},{"issue":"10","key":"coi260019r10","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1093\/annonc\/mdu276","article-title":"Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.","volume":"25","author":"Bosetti","year":"2014","journal-title":"Ann Oncol"},{"issue":"6","key":"coi260019r11","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1053\/j.gastro.2018.02.011","article-title":"Acute pancreatitis and pancreatic cancer risk: a nationwide matched-cohort study in Denmark.","volume":"154","author":"Kirkeg\u00e5rd","year":"2018","journal-title":"Gastroenterology"},{"issue":"11","key":"coi260019r12","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1038\/ajg.2012.288","article-title":"Alcohol and tobacco lower the age of presentation in sporadic pancreatic cancer in a dose-dependent manner: a multicenter study.","volume":"107","author":"Anderson","year":"2012","journal-title":"Am J Gastroenterol"},{"issue":"5","key":"coi260019r13","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/S0016-5085(03)00272-5","article-title":"Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds.","volume":"124","author":"Rulyak","year":"2003","journal-title":"Gastroenterology"},{"issue":"24","key":"coi260019r14","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1001\/jama.2009.886","article-title":"Body mass index and risk, age of onset, and survival in patients with pancreatic cancer.","volume":"301","author":"Li","year":"2009","journal-title":"JAMA"},{"issue":"3","key":"coi260019r15","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pkaa021","article-title":"Evaluating the utility of polygenic risk scores in identifying high-risk individuals for eight common cancers.","volume":"4","author":"Jia","year":"2020","journal-title":"J Natl Cancer Inst Cancer Spectr"},{"issue":"6","key":"coi260019r16","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1136\/jmedgenet-2020-106961","article-title":"Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction.","volume":"58","author":"Galeotti","year":"2021","journal-title":"J Med Genet"},{"issue":"7","key":"coi260019r17","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.annonc.2022.03.276","article-title":"The age-dependent association of risk factors with pancreatic cancer.","volume":"33","author":"Yuan","year":"2022","journal-title":"Ann Oncol"},{"issue":"3","key":"coi260019r18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age.","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med"},{"issue":"7","key":"coi260019r19","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.3390\/nu11071572","article-title":"Operationalizing the 2018 World Cancer Research Fund\/American Institute for Cancer Research (WCRF\/AICR) cancer prevention recommendations: a standardized scoring system.","volume":"11","author":"Shams-White","year":"2019","journal-title":"Nutrients"},{"issue":"12","key":"coi260019r20","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1002\/ijc.70064","article-title":"Thirteen simple lifestyle scores and risk of cancer, cardiovascular disease, diabetes, and mortality: Prospective cohort study in the UK Biobank.","volume":"157","author":"Ding","year":"2025","journal-title":"Int J Cancer"},{"issue":"9","key":"coi260019r22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162388","article-title":"Algorithms for the capture and adjudication of prevalent and incident diabetes in UK Biobank.","volume":"11","author":"Eastwood","year":"2016","journal-title":"PLoS One"},{"issue":"7726","key":"coi260019r23","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data.","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"issue":"1","key":"coi260019r24","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1038\/s41467-021-21288-z","article-title":"Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts.","volume":"12","author":"Graff","year":"2021","journal-title":"Nat Commun"},{"issue":"1","key":"coi260019r25","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/s41467-018-02942-5","article-title":"Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.","volume":"9","author":"Klein","year":"2018","journal-title":"Nat Commun"},{"issue":"6","key":"coi260019r26","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1053\/j.gastro.2022.01.016","article-title":"Predicting pancreatic cancer in the UK Biobank cohort using polygenic risk scores and diabetes mellitus.","volume":"162","author":"Sharma","year":"2022","journal-title":"Gastroenterology"},{"issue":"18","key":"coi260019r27","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.1001\/jama.1982.03320430047030","article-title":"Evaluating the yield of medical tests.","volume":"247","author":"Harrell","year":"1982","journal-title":"JAMA"},{"issue":"4","key":"coi260019r28","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-24-0142","article-title":"Discordant risk factors between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinoma.","volume":"32","author":"Chandra","year":"2025","journal-title":"Endocr Relat Cancer"},{"issue":"1","key":"coi260019r29","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1186\/s12916-023-03202-0","article-title":"Association of genetic risk and lifestyle with pancreatic cancer and their age dependency: a large prospective cohort study in the UK Biobank.","volume":"21","author":"Zeng","year":"2023","journal-title":"BMC Med"},{"issue":"6","key":"coi260019r30","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s10654-011-9554-9","article-title":"Estimating measures of interaction on an additive scale for preventive exposures.","volume":"26","author":"Knol","year":"2011","journal-title":"Eur J Epidemiol"},{"issue":"3","key":"coi260019r31","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.annepidem.2006.10.009","article-title":"Test for additive interaction in proportional hazards models.","volume":"17","author":"Li","year":"2007","journal-title":"Ann Epidemiol"},{"issue":"3","key":"coi260019r32","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/s43587-025-00827-z","article-title":"The complex interplay between aging and cancer.","volume":"5","author":"Trastus","year":"2025","journal-title":"Nat Aging"},{"issue":"1","key":"coi260019r33","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/EDE.0b013e318230e861","article-title":"Accounting for bias due to selective attrition: the example of smoking and cognitive decline.","volume":"23","author":"Weuve","year":"2012","journal-title":"Epidemiology"},{"issue":"5","key":"coi260019r34","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1136\/bmjebm-2018-110972","article-title":"\u2018Depletion of the susceptibles\u2019 taught through a story, a table and basic arithmetic.","volume":"23","author":"Stovitz","year":"2018","journal-title":"BMJ Evid Based Med"},{"issue":"3","key":"coi260019r35","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1093\/jnci\/djae260","article-title":"Glucagon-like peptide-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data.","volume":"117","author":"Wang","year":"2025","journal-title":"J Natl Cancer Inst"},{"issue":"4","key":"coi260019r36","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1136\/gutjnl-2024-333329","article-title":"Aspirin is associated with lower risk of pancreatic cancer and cancer-related mortality in patients with diabetes mellitus.","volume":"74","author":"Tan","year":"2025","journal-title":"Gut"},{"key":"coi260019r37","doi-asserted-by":"publisher","first-page":"828","DOI":"10.18632\/oncotarget.28242","article-title":"Early-onset pancreatic cancer: a review of molecular mechanisms, management, and survival.","volume":"13","author":"Ulanja","year":"2022","journal-title":"Oncotarget"},{"issue":"5","key":"coi260019r38","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s00423-019-01810-0","article-title":"Early-onset pancreatic cancer: a population-based study using the SEER registry.","volume":"404","author":"Ansari","year":"2019","journal-title":"Langenbecks Arch Surg"},{"issue":"3","key":"coi260019r39","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/ijc.35184","article-title":"Life\u2019s Essential 8, genetic susceptibility, and risk of incident pancreatic cancer: a prospective cohort study.","volume":"156","author":"Wu","year":"2025","journal-title":"Int J Cancer"},{"issue":"4","key":"coi260019r40","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1093\/oxfordjournals.aje.a113015","article-title":"Concepts of interaction.","volume":"112","author":"Rothman","year":"1980","journal-title":"Am J Epidemiol"},{"issue":"5","key":"coi260019r41","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1001\/jamainternmed.2020.0618","article-title":"Association of healthy lifestyle with years lived without major chronic diseases.","volume":"180","author":"Nyberg","year":"2020","journal-title":"JAMA Intern Med"},{"key":"coi260019r42","doi-asserted-by":"publisher","first-page":"i1102","DOI":"10.1136\/bmj.i1102","article-title":"The impact of communicating genetic risks of disease on risk-reducing health behaviour: systematic review with meta-analysis.","volume":"352","author":"Hollands","year":"2016","journal-title":"BMJ"},{"issue":"6","key":"coi260019r43","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1056\/NEJMoa1011893","article-title":"Effect of direct-to-consumer genomewide profiling to assess disease risk.","volume":"364","author":"Bloss","year":"2011","journal-title":"N Engl J Med"},{"key":"coi260019r44","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3389\/fcvm.2017.00053","article-title":"Impact of a genetic risk score for coronary artery disease on reducing cardiovascular risk: a pilot randomized controlled study.","volume":"4","author":"Knowles","year":"2017","journal-title":"Front Cardiovasc Med"},{"issue":"5","key":"coi260019r45","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1053\/j.gastro.2023.02.012","article-title":"Pancreatic cancer: changing epidemiology and new approaches to risk assessment, early detection, and prevention.","volume":"164","author":"Stoffel","year":"2023","journal-title":"Gastroenterology"},{"issue":"20","key":"coi260019r46","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1001\/jama.2021.18859","article-title":"Incidence of pancreatic cancer by age and sex in the US, 2000-2018.","volume":"326","author":"Gaddam","year":"2021","journal-title":"JAMA"},{"key":"coi260019r47","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1116905","article-title":"Longitudinal patterns of lifestyle risk behaviours among UK adults with established cardiovascular disease: a latent transition analysis.","volume":"10","author":"Tegegne","year":"2023","journal-title":"Front Cardiovasc Med"},{"issue":"8","key":"coi260019r48","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1080\/08870446.2024.2316676","article-title":"Stability in health behavior patterns in middle adulthood: a 19-year follow-up study.","volume":"40","author":"Ahola","year":"2025","journal-title":"Psychol Health"},{"issue":"9","key":"coi260019r49","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1093\/aje\/kwx246","article-title":"Comparison of sociodemographic and health-related characteristics of UK Biobank participants with those of the general population.","volume":"186","author":"Fry","year":"2017","journal-title":"Am J Epidemiol"},{"issue":"4","key":"coi260019r50","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1093\/ije\/dys223","article-title":"Why representativeness should be avoided.","volume":"42","author":"Rothman","year":"2013","journal-title":"Int J Epidemiol"},{"issue":"5","key":"coi260019r51","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1136\/jech.2009.107185","article-title":"Sample selection and validity of exposure-disease association estimates in cohort studies.","volume":"65","author":"Pizzi","year":"2011","journal-title":"J Epidemiol Community Health"},{"key":"coi260019r3","unstructured":"International Agency for Research on Cancer. Trends in cancer incidence and mortality rates. Accessed January 23, 2026. https:\/\/gco.iarc.who.int\/overtime\/en"},{"key":"coi260019r21","unstructured":"World Health Organization. Noncommunicable diseases global monitoring framework: indicator definitions and specifications. Accessed January 23, 2026. https:\/\/www.who.int\/publications\/m\/item\/noncommunicable-diseases-global-monitoring-framework-indicator-definitions-and-specifications"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2849069\/jamaoncology_ding_2026_oi_260019_1784081567.37861.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:00:59Z","timestamp":1784214059000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2849069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2026.1192","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7,1]]}}}