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Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between <jats:italic>BRM\u2010741\/BRM\u20101321<\/jats:italic> and risk in patients with MPM, a differential effect by smoking status was observed (<jats:italic>P<\/jats:italic>\u2010interaction\u2009&lt;\u2009.001), where homozygous variants were protective (aOR of 0.18\u20100.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7\u20104.4). While there was no association between <jats:italic>BRM<\/jats:italic> polymorphisms and OS in ever\u2010smokers, the aHR of carrying homozygous\u2010variants of <jats:italic>BRM\u2010741<\/jats:italic>, <jats:italic>BRM\u20101321<\/jats:italic> or both were 4.0 to 8.6 in never\u2010smokers when compared to wild\u2010type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA\u2010affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never\u2010smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever\u2010smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.<\/jats:p>","DOI":"10.1002\/mc.23088","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T12:10:20Z","timestamp":1564402220000},"page":"1960-1973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of two <i>BRM<\/i> promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2722-8526","authenticated-orcid":false,"given":"Min Joon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"},{"name":"Faculty of Medicine University of Toronto  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-8514","authenticated-orcid":false,"given":"Nathan","family":"Kuehne","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Hueniken","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shermi","family":"Liang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine University of Florida  Gainesville Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudhir","family":"Rai","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine University of Florida  Gainesville Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadas","family":"Sorotsky","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Herman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Shepshelovich","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Bruce","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mindy","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devalben","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dangxiao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawson","family":"Eng","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre University Health Network  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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