{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:24:49Z","timestamp":1780619089560,"version":"3.54.1"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T00:00:00Z","timestamp":1384905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>Endemic Burkitt lymphoma (eBL) is associated with Epstein\u2013Barr virus (EBV) and <jats:italic>Plasmodium falciparum<\/jats:italic> coinfections. Malaria appears to dysregulate immunity that would otherwise control EBV, thereby contributing to eBL etiology. Juxtaposed to human genetic variants associated with protection from malaria, it has been hypothesized that such variants could decrease eBL susceptibility, historically referred to as \u201cthe protective hypothesis.\u201d Past studies attempting to link sickle cell trait (HbAS), which is known to be protective against malaria, with protection from eBL were contradictory and underpowered. Therefore, using a case\u2013control study design, we examined HbAS frequency in 306 Kenyan children diagnosed with eBL compared to 537 geographically defined and ethnically matched controls. We found 23.8% HbAS for eBL patients, which was not significantly different compared to 27.0% HbAS for controls [odds ratio (OR)\u2009=\u20090.85; 95% confidence interval (CI) 0.61\u20131.17; <jats:italic>p<\/jats:italic>\u2010value\u2009=\u20090.33]. Even though cellular EBV titers, indicative of the number of latently infected B cells, were significantly higher (<jats:italic>p<\/jats:italic>\u2010value\u2009&lt;\u20090.0003) in children residing in malaria holoendemic compared to hypoendemic areas, levels were not associated with HbAS genotype. Combined, this suggests that although HbAS protects against severe malaria and hyperparasitemia, it is not associated with viral control or eBL protection. However, based on receiver operating characteristic curves factors that enable the establishment of EBV persistence, in contrast to those involved in EBV lytic reactivation, may have utility as an eBL precursor biomarker. This has implications for future human genetic association studies to consider variants influencing control over EBV in addition to malaria as risk factors for eBL.<\/jats:p>","DOI":"10.1002\/ijc.28378","type":"journal-article","created":{"date-parts":[[2013,7,5]],"date-time":"2013-07-05T17:20:49Z","timestamp":1373044849000},"page":"645-653","source":"Crossref","is-referenced-by-count":39,"title":["Sickle cell trait is not associated with endemic Burkitt lymphoma: An ethnicity and malaria endemicity\u2010matched case\u2013control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer"],"prefix":"10.1002","volume":"134","author":[{"given":"David H.","family":"Mulama","sequence":"first","affiliation":[{"name":"Center for Global Health Research Kenyan Medical Research Institute Kisumu Kenya"},{"name":"Department of Biomedical Sciences and Technology Maseno University Maseno Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Medicine and Program in Bioinformatics &amp; Computational Biology University of Massachusetts Medical School Worcester MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joslyn","family":"Foley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Massachusetts Medical School Worcester MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiprotich","family":"Chelimo","sequence":"additional","affiliation":[{"name":"Center for Global Health Research Kenyan Medical Research Institute Kisumu Kenya"},{"name":"Department of Biomedical Sciences and Technology Maseno University Maseno Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collins","family":"Ouma","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Technology Maseno University Maseno Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter G.Z.O.","family":"Jura","sequence":"additional","affiliation":[{"name":"Department of Zoology Maseno University Maseno Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Otieno","sequence":"additional","affiliation":[{"name":"Jaramogi Oginga Odinga Teaching and Referral Hospital Ministry of Medical Services Kisumu Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Vulule","sequence":"additional","affiliation":[{"name":"Center for Global Health Research Kenyan Medical Research Institute Kisumu Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Moormann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Massachusetts Medical School Worcester MA"},{"name":"Department of Quantitative Health Sciences University of Massachusetts Medical School Worcester MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,20]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"177","article-title":"Epidemiological evidence for the role of falciparum malaria in the pathogenesis of Burkitt's lymphoma","author":"Morrow RH","year":"1985","journal-title":"IARC Sci Publ"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1089"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/428910"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/511984"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-7-238"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24014"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.9.5412-5418.2004"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2008.78.338"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0909-957"},{"key":"e_1_2_7_11_1","first-page":"39","article-title":"Burkitt's lymphoma and sickle cell trait","volume":"24","author":"Pike MC","year":"1970","journal-title":"Br J Prev Soc Med"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2009.01106.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/180326a0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(54)90101-7"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.06.009"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08273-9"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(67)91037-9"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.3.3.177"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1976.25.633"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.582"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01252-07"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2007.01875.x"},{"key":"e_1_2_7_23_1","first-page":"S68","article-title":"Burkitt's lymphoma in Kenya: geographical, age, gender and ethnic distribution","author":"Mwanda OW","year":"2004","journal-title":"East Afr Med J"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(03)80010-X"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir872"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1994.1023"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)91137-0"},{"key":"e_1_2_7_28_1","first-page":"249","article-title":"A comparative study of thick and thin blood films in the diagnosis of scanty malaria parasitaemia","volume":"34","author":"Dowling MAC","year":"1966","journal-title":"Bull World Health Organ"},{"key":"e_1_2_7_29_1","first-page":"273","article-title":"Analysis of sickle cell gene using polymerase chain reaction & restriction enzyme Bsu 361","volume":"101","author":"Husain SM","year":"1995","journal-title":"Indian J Med Res"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019606-200406000-00001"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4857.294"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-371062"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/500839"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/312449a0"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910310609"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1990.tb05236.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90203-2"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1086\/594373"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031753"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.4.1211-1216.2001"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1086\/430744"},{"key":"e_1_2_7_42_1","first-page":"553","article-title":"How genetics and biology helped humanity to survive falciparum malaria","volume":"48","author":"Arese P","year":"2006","journal-title":"Parassitologia"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-241844"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e328349ac4f"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990820)84:4<442::AID-IJC20>3.0.CO;2-J"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.2165\/00066982-200106040-00009"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.6310"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190310001623801"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2008"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031142"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.28378","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.28378","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.28378","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.28378","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T14:30:20Z","timestamp":1696343420000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.28378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,20]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1002\/ijc.28378"],"URL":"https:\/\/doi.org\/10.1002\/ijc.28378","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,20]]}}}