{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:36:42Z","timestamp":1790836602947,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012797","name":"NorthShore University HealthSystem","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012797","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJUI Compass"],"published-print":{"date-parts":[[2023,3]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n To evaluate which of previously reported monogenic genes are associated with increased bladder cancer risk, we reviewed published papers on associations of genes and bladder cancer risk and performed a confirmation study of these genes in a large population\u2010based cohort.<\/jats:p>\n <\/jats:sec>\n \n Subjects and methods<\/jats:title>\n A systematic review of published papers prior to June 2022 was performed first to identify all genes where germline mutations were associated with bladder cancer risk. The associations of these candidate genes with bladder cancer risk were then tested among 1695 bladder cancer cases and 186\u2009271 controls in the UK Biobank (UKB). The robust SKAT\u2010O, a gene\u2010based analysis that properly controls for type I error rates due to unbalanced case\u2013control ratio, was used for association tests adjusting for age at recruitment, gender, smoking status, and genetic background.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The systematic review identified nine genes that were significantly associated with bladder cancer risk in at least one study (\n p<\/jats:italic>\n \u00a0<\u20090.05), including\n MUTYH<\/jats:italic>\n ,\n MSH2<\/jats:italic>\n ,\n MSH6<\/jats:italic>\n ,\n MLH1<\/jats:italic>\n ,\n ATM<\/jats:italic>\n ,\n BRCA2<\/jats:italic>\n ,\n ERCC5<\/jats:italic>\n ,\n TGFB1<\/jats:italic>\n and\n CHEK2<\/jats:italic>\n . When pathogenic\/likely pathogenic mutations were aggregated within each gene, the association was confirmed for three genes in the UKB at\n p<\/jats:italic>\n \u00a0<\u20090.0056 (Bonferroni correction for nine tests), including\n CHEK2<\/jats:italic>\n ,\n ATM<\/jats:italic>\n and\n BRCA2<\/jats:italic>\n , all also known to be associated with hereditary breast cancer. Suggestive evidence of association was found for two other genes, including\n MLH1<\/jats:italic>\n (\n p<\/jats:italic>\n \u00a0=\u20090.006) and\n MSH2<\/jats:italic>\n (\n p<\/jats:italic>\n \u00a0=\u20090.007), both known to be associated with Lynch syndrome. Among these five genes, the bladder cancer risks range from 1.60 (\n ATM<\/jats:italic>\n ) to 4.88 (\n MLH1<\/jats:italic>\n ), and mutation carrier rates in cases range from 0.06% (\n MSH2<\/jats:italic>\n ) to 2.01% (\n CHEK2<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This study provides statistical evidence for association of previously reported genes and bladder cancer risk and has clinical utility for risk assessment and genetic counselling.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/bco2.206","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T17:00:31Z","timestamp":1670432431000},"page":"156-163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Systematic review of reported association studies of monogenic genes and bladder cancer risk and confirmation analysis in a large population cohort"],"prefix":"10.1002","volume":"4","author":[{"given":"Abrar","family":"Mian","sequence":"first","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"},{"name":"Midwestern University Chicago College of Osteopathic Medicine Downers Grove Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Rifkin","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Lilly","family":"Zheng","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander P.","family":"Glaser","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"},{"name":"Department of Surgery NorthShore University HealthSystem Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5416-4671","authenticated-orcid":false,"given":"James T.","family":"Kearns","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"},{"name":"Department of Surgery NorthShore University HealthSystem Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T.","family":"Helfand","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"},{"name":"Department of Surgery NorthShore University HealthSystem Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-8752","authenticated-orcid":false,"given":"Jianfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA"},{"name":"Department of Surgery NorthShore University HealthSystem Evanston Illinois USA"},{"name":"Department of Surgery University of Chicago Pritzker School of Medicine Chicago Illinois 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