학술논문
IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa.
Document Type
Academic Journal
Author
Baker FS; Laboratory of Translational Genomics, National Cancer Institute, Rockville, Maryland, USA.; Wang J; Laboratory of Translational Genomics, National Cancer Institute, Rockville, Maryland, USA.; Florez-Vargas O; Laboratory of Translational Genomics, National Cancer Institute, Rockville, Maryland, USA.; Brand NR; Department of Surgery, University of California, San Francisco, California, USA.; Ogwang MD; EMBLEM Study, St. Mary's Hospital, Lacor, Uganda.; EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.; Kerchan P; EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.; EMBLEM Study, Kuluva Hospital, Arua, Uganda.; Reynolds SJ; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Tenge CN; EMBLEM Study, Moi University College of Health Sciences, Eldoret, Kenya.; Were PA; EMBLEM Study, Academic Model Providing Access To Healthcare (AMPATH), Eldoret, Kenya.; Kuremu RT; EMBLEM Study, Moi University College of Health Sciences, Eldoret, Kenya.; Wekesa WN; EMBLEM Study, Moi University College of Health Sciences, Eldoret, Kenya.; Masalu N; EMBLEM Study, Bugando Medical Center, Mwanza, Tanzania.; Kawira E; EMBLEM Study, Shirati Health, Education, and Development Foundation, Shirati, Tanzania.; Kinyera T; EMBLEM Study, St. Mary's Hospital, Lacor, Uganda.; EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.; Otim I; EMBLEM Study, St. Mary's Hospital, Lacor, Uganda.; EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.; Legason ID; EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.; EMBLEM Study, Kuluva Hospital, Arua, Uganda.; Nabalende H; EMBLEM Study, St. Mary's Hospital, Lacor, Uganda.; EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.; Chagaluka G; Department of Pediatrics and Surgery, Kamuzu University of Health Sciences, Blantyre, Malawi.; Mutalima N; Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York, United Kingdom.; Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.; Borgstein E; Department of Pediatrics and Surgery, Kamuzu University of Health Sciences, Blantyre, Malawi.; Liomba GN; Department of Pediatrics and Surgery, Kamuzu University of Health Sciences, Blantyre, Malawi.; Kamiza S; Department of Pediatrics and Surgery, Kamuzu University of Health Sciences, Blantyre, Malawi.; Mkandawire N; Department of Pediatrics and Surgery, Kamuzu University of Health Sciences, Blantyre, Malawi.; Mitambo C; Research Department, Ministry of Health, Lilongwe, Malawi.; Molyneux EM; Department of Pediatrics and Surgery, Kamuzu University of Health Sciences, Blantyre, Malawi.; Newton R; Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York, United Kingdom.; Prokunina-Olsson L; Laboratory of Translational Genomics, National Cancer Institute, Rockville, Maryland, USA.; Mbulaiteye SM; Laboratory of Translational Genomics, National Cancer Institute, Rockville, Maryland, USA.
Source
Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 9507088 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-7465 (Electronic) Linking ISSN: 10799907 NLM ISO Abbreviation: J Interferon Cytokine Res Subsets: MEDLINE
Subject
Language
English
Abstract
Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele ( IFNL4 -dG) is most common (up to 78%) in West sub-Saharan Africa (SSA), compared to 35% of Europeans and 5% of individuals from East Asia. The negative selection of IFNL4 -dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case-control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6-9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4 -dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.