{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:17:23Z","timestamp":1792066643123,"version":"4.4.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24POST1189614"],"award-info":[{"award-number":["24POST1189614"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2017-00644"],"award-info":[{"award-number":["2017-00644"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2021-00160"],"award-info":[{"award-number":["2021-00160"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2017-06100"],"award-info":[{"award-number":["2017-06100"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004200","name":"Stiftelsen Olle Engkvist Byggm\u00e4stare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004200","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Academic Infrastructure for Supercomputing in Sweden"},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The causes of bladder cancer are not completely understood. Our objective was to identify blood proteins and modifiable causal risk factors for bladder cancer by combining genome-wide association study (GWAS) and Mendelian randomization (MR) analyses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We first performed a GWAS meta-analysis of 6984 bladder cancer\u00a0case patients and 708\u00a0432 control individuals from 3 European databases. Next, we conducted 2-sample MR and colocalization analyses using data from the present GWAS and published GWAS meta-analyses on plasma proteins and modifiable factors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Genome-wide association study meta-analysis uncovered 17 bladder cancer susceptibility loci, of which 3 loci were novel. Genes were enriched in pathways related to the metabolic and catabolic processes of xenobiotics and cellular detoxification. Proteome-wide MR analysis based on cis-acting genetic variants revealed that higher plasma levels of glutathione S-transferases were strongly associated with a reduced risk of bladder cancer. There is strong evidence of colocalization between GSTM1 and bladder cancer. Finally, multivariable MR analyses of suspected risk factors for bladder cancer revealed independent causal associations between smoking and adiposity, particularly abdominal obesity, and risk of bladder cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Findings from this large-scale GWAS and multivariable MR analyses highlight the key role of detoxification processes, particularly glutathione S-transferase 1, as well as smoking and abdominal obesity in bladder cancer etiology.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jncics\/pkaf014","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T14:51:01Z","timestamp":1738594261000},"source":"Crossref","is-referenced-by-count":9,"title":["Genome-wide association study and Mendelian randomization analyses reveal insights into bladder cancer etiology"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-0341","authenticated-orcid":false,"given":"Susanna C","family":"Larsson","sequence":"first","affiliation":[{"name":"Medical Epidemiology, Department of Surgical Sciences, Uppsala University , Uppsala,","place":["Sweden"]},{"name":"Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4029-4192","authenticated-orcid":false,"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4937-9168","authenticated-orcid":false,"given":"Xixian","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Third Xiangya Hospital, Central South University , Changsha,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-2577","authenticated-orcid":false,"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5055-5627","authenticated-orcid":false,"given":"Shuai","family":"Yuan","sequence":"additional","affiliation":[{"name":"Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"2025050520514443700_pkaf014-B1","doi-asserted-by":"publisher","first-page":"e004128","DOI":"10.1136\/bmjgh-2020-004128","article-title":"Global, regional and national burden of bladder cancer and its attributable risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease study 2019","volume":"6","author":"Safiri","year":"2021","journal-title":"BMJ Glob 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