Maneet Kaur1, Adam J de Smith2, Steve Selvin3, Luoping Zhang4, Marc Cunningham2, Michelle W Kang2, Helen M Hansen5, Robert M Cooper6, Roberta McKean-Cowdin7, Joseph L Wiemels8, Catherine Metayer9. 1. Division of Epidemiology, School of Public Health, University of California Berkeley, Berkeley, California. 2. Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. 3. Divison of Biostatistics, School of Public Health, University of California Berkeley, Berkeley, California. 4. Division of Environmental Health Sciences, School of Public Health, University of California Berkeley, Berkeley, California. 5. Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. 6. Department of Pediatric Hematology/Oncology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California. 7. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. 8. Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California; Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. 9. Division of Epidemiology, School of Public Health, University of California Berkeley, Berkeley, California. Electronic address: cmetayer@berkeley.edu.
Abstract
BACKGROUND AND AIMS: Childhood acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease, and mutations in the KRAS and NRAS oncogenes are present at diagnosis in about one-fifth of cases. Ras mutations were previously associated with environmental exposures in leukemias as well as in many other cancer types. This study examined whether Ras mutation could define a unique etiologic group of childhood ALL associated with tobacco smoke, a well-established mutagen and carcinogen. METHODS: We included 670 children with ALL enrolled in a case-control study in California (1995-2013), including 50.6% Latinos. Parental and child exposure to tobacco smoke was obtained from interviews. Sanger sequencing was used to detect the common KRAS and NRAS hotspot mutations in diagnostic bone marrow DNA. ALL cases were also characterized for common chromosome abnormalities. In case-case analyses, logistic regression analyses were used to estimate odds ratios to describe the association between tobacco smoke exposure and childhood ALL with Ras mutations. RESULTS: KRAS or NRAS mutations were detected in ∼18% of children diagnosed with ALL. Ras mutations were more common among Latino cases compared with non-Latino whites and in high-hyperdiploid ALL. No associations were observed between parental smoking or child's passive exposure to smoke and Ras positive ALL. CONCLUSIONS: The apparent lack of association between tobacco smoke and Ras mutation in childhood ALL suggests that Ras mutations do not specifically define a tobacco-related etiologic pathway. Reasons for racial and ethnic differences in ALL are not well understood and could reflect differences in etiology that warrant further examination.
BACKGROUND AND AIMS: Childhood acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease, and mutations in the KRAS and NRAS oncogenes are present at diagnosis in about one-fifth of cases. Ras mutations were previously associated with environmental exposures in leukemias as well as in many other cancer types. This study examined whether Ras mutation could define a unique etiologic group of childhood ALL associated with tobacco smoke, a well-established mutagen and carcinogen. METHODS: We included 670 children with ALL enrolled in a case-control study in California (1995-2013), including 50.6% Latinos. Parental and child exposure to tobacco smoke was obtained from interviews. Sanger sequencing was used to detect the common KRAS and NRAS hotspot mutations in diagnostic bone marrow DNA. ALL cases were also characterized for common chromosome abnormalities. In case-case analyses, logistic regression analyses were used to estimate odds ratios to describe the association between tobacco smoke exposure and childhood ALL with Ras mutations. RESULTS:KRAS or NRAS mutations were detected in ∼18% of children diagnosed with ALL. Ras mutations were more common among Latino cases compared with non-Latino whites and in high-hyperdiploid ALL. No associations were observed between parental smoking or child's passive exposure to smoke and Ras positive ALL. CONCLUSIONS: The apparent lack of association between tobacco smoke and Ras mutation in childhood ALL suggests that Ras mutations do not specifically define a tobacco-related etiologic pathway. Reasons for racial and ethnic differences in ALL are not well understood and could reflect differences in etiology that warrant further examination.
Authors: Elizabeth Milne; Kathryn R Greenop; Rodney J Scott; Helen D Bailey; John Attia; Luciano Dalla-Pozza; Nicholas H de Klerk; Bruce K Armstrong Journal: Am J Epidemiol Date: 2011-12-05 Impact factor: 4.897
Authors: F Chang; L S Steelman; J T Lee; J G Shelton; P M Navolanic; W L Blalock; R A Franklin; J A McCubrey Journal: Leukemia Date: 2003-07 Impact factor: 11.528
Authors: Melinda C Aldrich; Luoping Zhang; Joseph L Wiemels; Xiaomei Ma; Mignon L Loh; Catherine Metayer; Steve Selvin; James Feusner; Martyn T Smith; Patricia A Buffler Journal: Cancer Epidemiol Biomarkers Prev Date: 2006-03 Impact factor: 4.254
Authors: Marco Tartaglia; Simone Martinelli; Giovanni Cazzaniga; Viviana Cordeddu; Ivano Iavarone; Monica Spinelli; Chiara Palmi; Claudio Carta; Andrea Pession; Maurizio Aricò; Giuseppe Masera; Giuseppe Basso; Mariella Sorcini; Bruce D Gelb; Andrea Biondi Journal: Blood Date: 2004-02-24 Impact factor: 22.113
Authors: Matthew North; Joe Shuga; Michele Fromowitz; Alexandre Loguinov; Kevin Shannon; Luoping Zhang; Martyn T Smith; Chris D Vulpe Journal: BMC Cancer Date: 2014-01-05 Impact factor: 4.430
Authors: Lindsay A Williams; Jun J Yang; Betsy A Hirsch; Erin L Marcotte; Logan G Spector Journal: Cancer Epidemiol Biomarkers Prev Date: 2019-02-15 Impact factor: 4.254