PMID- 29206312 OWN - NLM STAT- MEDLINE DCOM- 20191212 LR - 20191217 IS - 1098-2280 (Electronic) IS - 0893-6692 (Linking) VI - 60 IP - 5 DP - 2019 Jun TI - Risk of cancer in children exposed to antiretroviral nucleoside analogues in utero: The french experience. PG - 404-409 LID - 10.1002/em.22162 [doi] AB - All nucleoside analogues for treating HIV infection, due to their capacity to integrate into and alter human DNA, are experimentally genotoxic to some extent. The long-term oncogenic risk after in utero exposure remains to be determined. Cancer incidence in uninfected children exposed to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) was evaluated, by cross-checking against the National Cancer Registry, in the French perinatal study of children born to HIV(+) mothers. Twenty-one cancers were identified in 15,163 children (median age: 9.9 years [interquartile range (IQR): 5.8-14.2]) exposed to at least one NRTI in utero between 1990 and 2014. Five of these children were exposed to zidovudine monotherapy, and 15 to various combinations, seven of which included didanosine. Overall, the total number of cases was not significantly different from that expected for the general population (SIR = 0.8[0.47-1.24]), but the number of cases after didanosine exposure was twice that expected (SIR = 2.5 [1.01-5.19]). Didanosine accounted for only 10% of prescriptions but was associated with one-third of cancers. In multivariate analysis, didanosine exposure was significantly associated with higher risk (HR = 3.0 [0.9-9.8]). This risk was specifically linked to first-trimester exposure (HR = 5.5 [2.1-14.4]). Three cases of pineoblastoma, a very rare cancer, were observed, whereas 0.03 were expected. Two were associated with didanosine exposure. Despite reassuring data overall, there is strong evidence to suggest that didanosine displays transplacental oncogenicity. These findings cannot be extrapolated to other NRTIs, but they highlight the need for comprehensive evaluations of the transplacental genotoxicity of this antiretroviral class. Environ. Mol. Mutagen., 60:404-409, 2019. (c) 2017 Wiley Periodicals, Inc. CI - (c) 2017 Wiley Periodicals, Inc. FAU - Hleyhel, Mira AU - Hleyhel M AD - Epidemiology and Population Health Center, Institut National de la Sante et de la Recherche Medicale (INSERM), Le Kremlin-Bicetre, U1018, France. FAU - Goujon, Stephanie AU - Goujon S AD - Epidemiology of Childhood and Adolescent Cancers Team (EPICEA), Universite Paris Descartes, Epidemiology and Biostatistics, INSERM UMR1153, Sorbonne Paris Cite Research Center, Villejuif, France. AD - French National Registry of Childhood Cancers, Villejuif, France. FAU - Sibiude, Jeanne AU - Sibiude J AD - Gynecology and Obstetrics Department, Hopital Louis Mourier, Hopitaux Universitaires Paris Nord Val de Seine, AP-HP, Colombes, France. FAU - Tubiana, Roland AU - Tubiana R AD - Infectious Diseases Department, Hopital Pitie Salpetriere, Assistance Publique-Hopitaux de Paris (AP-HP), Paris, France. FAU - Dollfus, Catherine AU - Dollfus C AD - Pediatric Department, Hopital Trousseau, AP-HP, Paris, France. FAU - Faye, Albert AU - Faye A AD - Pediatric Department, Hopital Robert Debre, AP-HP, Universite Paris Diderot, Sorbonne Paris-Cite, Paris, France. FAU - Mandelbrot, Laurent AU - Mandelbrot L AD - Gynecology and Obstetrics Department, Hopital Louis Mourier, Hopitaux Universitaires Paris Nord Val de Seine, AP-HP, Colombes, France. FAU - Clavel, Jacqueline AU - Clavel J AD - Epidemiology of Childhood and Adolescent Cancers Team (EPICEA), Universite Paris Descartes, Epidemiology and Biostatistics, INSERM UMR1153, Sorbonne Paris Cite Research Center, Villejuif, France. AD - French National Registry of Childhood Cancers, Villejuif, France. FAU - Warszawski, Josiane AU - Warszawski J AD - Epidemiology and Population Health Center, Institut National de la Sante et de la Recherche Medicale (INSERM), Le Kremlin-Bicetre, U1018, France. AD - Hopital Bicetre, AP-HP, Universite Paris Sud, Le Kremlin-Bicetre, France. FAU - Blanche, Stephane AU - Blanche S AD - Immunology Hematology Rheumatology Unit, Pediatric Department, Hopital Necker-Enfants Malades AP-HP, Universite Paris Descartes, Paris, France. CN - ANRS French Perinatal Cohort study Group LA - eng GR - Agence Nationale de Recherches sur le Sida et les Hepatites Virales/International GR - Agence Nationale de Securite du Medicament et des Produits de Sante/International GR - Societe Francaise des cancers de l'enfant et de l'adolescent/International PT - Journal Article PT - Multicenter Study DEP - 20171205 PL - United States TA - Environ Mol Mutagen JT - Environmental and molecular mutagenesis JID - 8800109 RN - 0 (Anti-HIV Agents) RN - 0 (Nucleosides) RN - 0 (Reverse Transcriptase Inhibitors) RN - 4B9XT59T7S (Zidovudine) RN - K3GDH6OH08 (Didanosine) SB - IM MH - Adolescent MH - Anti-HIV Agents/therapeutic use/*toxicity MH - Child MH - Child, Preschool MH - Didanosine/therapeutic use/toxicity MH - Female MH - HIV Infections/drug therapy MH - Humans MH - Incidence MH - Infant MH - Infant, Newborn MH - Male MH - *Maternal Exposure MH - Maternal-Fetal Exchange/*physiology MH - Neoplasms/*epidemiology/genetics MH - Nucleosides/therapeutic use/*toxicity MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*pathology MH - Prospective Studies MH - Reverse Transcriptase Inhibitors/therapeutic use/toxicity MH - Risk MH - Surveys and Questionnaires MH - Zidovudine/therapeutic use/toxicity OTO - NOTNLM OT - HIV OT - antiretroviral OT - cancer OT - didanosine OT - foetus OT - pregnancy EDAT- 2017/12/06 06:00 MHDA- 2019/12/18 06:00 CRDT- 2017/12/06 06:00 PHST- 2017/09/04 00:00 [received] PHST- 2017/11/03 00:00 [revised] PHST- 2017/11/15 00:00 [accepted] PHST- 2017/12/06 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2017/12/06 06:00 [entrez] AID - 10.1002/em.22162 [doi] PST - ppublish SO - Environ Mol Mutagen. 2019 Jun;60(5):404-409. doi: 10.1002/em.22162. Epub 2017 Dec 5.