{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:37Z","timestamp":1787027737602,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"publisher","award":["W81XWH1810570"],"award-info":[{"award-number":["W81XWH1810570"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006293","name":"American Society of Clinical Oncology","doi-asserted-by":"publisher","award":["Career Development Award"],"award-info":[{"award-number":["Career Development Award"]}],"id":[{"id":"10.13039\/100006293","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007313","name":"The University of Texas MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["Khalifa Scholar Award"],"award-info":[{"award-number":["Khalifa Scholar Award"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007313","name":"The University of Texas MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["Physician-Scientist Award"],"award-info":[{"award-number":["Physician-Scientist Award"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007313","name":"The University of Texas MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["Andrew Sabin Family Fellowship"],"award-info":[{"award-number":["Andrew Sabin Family Fellowship"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Renal medullary carcinoma (RMC) is a lethal malignancy affecting individuals with sickle hemoglobinopathies. Currently, no modifiable risk factors are known. We aimed to determine whether high-intensity exercise is a risk factor for RMC in individuals with sickle cell trait (SCT). We used multiple approaches to triangulate our conclusion. First, a case-control study was conducted at a single tertiary-care facility. Consecutive patients with RMC were compared to matched controls with similarly advanced genitourinary malignancies in a 1:2 ratio and compared on rates of physical activity and anthropometric measures, including skeletal muscle surface area. Next, we compared the rate of military service among our RMC patients to a similarly aged population of black individuals with SCT in the U.S. Further, we used genetically engineered mouse models of SCT to study the impact of exercise on renal medullary hypoxia. Compared with matched controls, patients with RMC reported higher physical activity and had higher skeletal muscle surface area. A higher proportion of patients with RMC reported military service than expected compared to the similarly-aged population of black individuals with SCT. When exposed to high-intensity exercise, mice with SCT demonstrated significantly higher renal medulla hypoxia compared to wild-type controls. These data suggest high-intensity exercise is the first modifiable risk factor for RMC in individuals with SCT.<\/jats:p>","DOI":"10.3390\/cancers13236022","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T04:48:37Z","timestamp":1638247717000},"page":"6022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Association of High-Intensity Exercise with Renal Medullary Carcinoma in Individuals with Sickle Cell Trait: Clinical Observations and Experimental Animal Studies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4079-9051","authenticated-orcid":false,"given":"Daniel D.","family":"Shapiro","sequence":"first","affiliation":[{"name":"Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-898X","authenticated-orcid":false,"given":"Melinda","family":"Soeung","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Perelli","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Dondossola","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devaki Shilpa","family":"Surasi","sequence":"additional","affiliation":[{"name":"Department of Nuclear Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durga N.","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Bertocchio","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Starbuck","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Van Alstine","sequence":"additional","affiliation":[{"name":"The Ronin Project, San Mateo, CA 94402, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew H. G.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan H.","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9007-0621","authenticated-orcid":false,"given":"Amishi Y.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-3320","authenticated-orcid":false,"given":"Alessandro","family":"Carugo","sequence":"additional","affiliation":[{"name":"Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION), The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Heffernan","sequence":"additional","affiliation":[{"name":"Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION), The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-0514","authenticated-orcid":false,"given":"Keri L.","family":"Schadler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Logothetis","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl L.","family":"Walker","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Karam","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-9610","authenticated-orcid":false,"given":"Giulio F.","family":"Draetta","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION), The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nizar M.","family":"Tannir","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giannicola","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6505-8308","authenticated-orcid":false,"given":"Pavlos","family":"Msaouel","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00000478-199501000-00001","article-title":"Renal medullary carcinoma\u2013The 7th sickle-cell nephropathy","volume":"19","author":"Davis","year":"1995","journal-title":"Am. J. Surg. 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