{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:38:05Z","timestamp":1778891885543,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T00:00:00Z","timestamp":1595548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00011\/1"],"award-info":[{"award-number":["MC_UU_00011\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It has been hypothesised that nonsyndromic cleft lip\/palate (nsCL\/P) and cancer may share aetiological risk factors. Population studies have found inconsistent evidence for increased incidence of cancer in nsCL\/P cases, but several genes (e.g., <jats:italic>CDH1<\/jats:italic>, <jats:italic>AXIN2<\/jats:italic>) have been implicated in the aetiologies of both phenotypes. We aimed to evaluate shared genetic aetiology between nsCL\/P and oral cavity\/oropharyngeal cancers (OC\/OPC), which affect similar anatomical regions. Using a primary sample of 5,048 OC\/OPC cases and 5,450 controls of European ancestry and a replication sample of 750 cases and 336,319 controls from UK Biobank, we estimate genetic overlap using nsCL\/P polygenic risk scores (PRS) with Mendelian randomization analyses performed to evaluate potential causal mechanisms. In the primary sample, we found strong evidence for an association between a nsCL\/P PRS and increased odds of OC\/OPC (per standard deviation increase in score, odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.04, 1.13; <jats:italic>p<\/jats:italic>\u2009=\u2009.000053). Although confidence intervals overlapped with the primary estimate, we did not find confirmatory evidence of an association between the PRS and OC\/OPC in UK Biobank (OR 1.02; 95% CI: 0.95, 1.10; <jats:italic>p<\/jats:italic>\u2009=\u2009.55). Mendelian randomization analyses provided evidence that major nsCL\/P risk variants are unlikely to influence OC\/OPC. Our findings suggest possible shared genetic influences on nsCL\/P and OC\/OPC.<\/jats:p>","DOI":"10.1002\/gepi.22343","type":"journal-article","created":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T05:58:15Z","timestamp":1595656695000},"page":"924-933","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluating shared genetic influences on nonsyndromic cleft lip\/palate and oropharyngeal neoplasms"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2819-9686","authenticated-orcid":false,"given":"Laurence J.","family":"Howe","sequence":"first","affiliation":[{"name":"Medical Research Council Integrative Epidemiology Unit, Population Health Sciences University of Bristol Bristol UK"},{"name":"Institute of Cardiovascular Science University College London London UK"},{"name":"Max Planck Institute for Psycholinguistics Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gibran","family":"Hemani","sequence":"additional","affiliation":[{"name":"Medical Research Council Integrative Epidemiology Unit, Population Health Sciences University of Bristol Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina","family":"Lesseur","sequence":"additional","affiliation":[{"name":"Section of Genetics International Agency for Research on Cancer Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Gaborieau","sequence":"additional","affiliation":[{"name":"Section of Genetics International Agency for Research on Cancer Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin U.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Mangold","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Brennan","sequence":"additional","affiliation":[{"name":"Section of Genetics International Agency for Research on Cancer Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy R.","family":"Ness","sequence":"additional","affiliation":[{"name":"NIHR Bristol Biomedical Research Centre University Hospitals Bristol Bristol UK"},{"name":"Weston NHS Foundation Trust University of Bristol Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"St Pourcain","sequence":"additional","affiliation":[{"name":"Medical Research Council Integrative Epidemiology Unit, Population Health Sciences University of Bristol Bristol UK"},{"name":"Max Planck Institute for Psycholinguistics Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Davey Smith","sequence":"additional","affiliation":[{"name":"Medical Research Council Integrative Epidemiology Unit, Population Health Sciences University of Bristol Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah J.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Medical Research Council Integrative Epidemiology Unit, Population Health Sciences University of Bristol Bristol 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