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Research

CLIC’s accomplishments include over 40 completed and ongoing pooling projects to investigate the role of environmental and genetic factors in acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), brain tumors, and embryonal tumors. In addition, CLIC researchers are continually thinking of new research ideas and proposing new pooled analyses to investigate childhood leukemias and solid tumors. CLIC’s current publications are listed below along with summaries of the major findings.

Published Articles as of November 2024

Folate metabolism and risk of childhood acute lymphoblastic leukemia: a genetic pathway analysis from the Childhood Cancer and Leukemia International Consortium.

Authors: Metayer C, Spector LG, Scheurer ME, Jeon S, Scott RJ, Takagi M, Clavel J, Manabe A, Ma X, Hailu EM, Lupo PJ, Urayama KY, Bonaventure A, Kato M, Meirhaeghe A, Chiang CWK, Morimoto LM, Wiemels JL.

Published In: Cancer Epidemiol Biomarkers Prev. 2024 Jun 21. doi: 10.1158/1055-9965.EPI-24-0189. Epub ahead of print. PMID: 38904462.

Summary: In previous pooled analyses, CLIC investigators showed that self-reported prenatal folate and vitamin supplementation reduces the risk of childhood leukemia. However, this follow-up CLIC metanalysis of ~ 2,900 genes variants involved in the folate metabolism pathway did not reveal associations with childhood leukemia risk. Other mechanisms such as gene-folate interaction, DNA methylation or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium (CLIC)

Authors: Lupo PJ, Chambers TM, Mueller BA, Clavel J, Dockerty JD, Doody DR, Erdmann F, Ezzat S, Filippini T, Hansen J, Heck JE, Infante-Rivard C, Kang AY, Magnani C, Malagoli C, Metayer C, Bailey HD, Mora AM, Ntzani E, Petridou ET, Pombo-de-Oliveira MS, Rashed WM, Roman E, Schüz J, Wesseling C, Spector LG, Scheurer ME.

Published In: Int J Cancer. 2024 Feb 1;154(3):434-447. doi: 10.1002/ijc.34720. Epub 2023 Sep 11. PMID: 37694915.

Summary: Little is known about childhood leukemia risk in children born with birth defects; therefore, we sought to identify new birth defect-leukemia patterns using data in the Childhood Cancer and Leukemia International Consortium. Certain birth defects, including those that affect the heart, were strongly associated with increased leukemia risk. Overall, our results point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

Authors: Schraw JM, Petridou ET, Bonaventure A, Dockerty JD, Karalexi M, Ntzani E, Infante-Rivard C, Clavel J, Bracci PM, McKean-Cowdin R, Roman E, Kane E, Erdmann F, Schüz J, Mueller BA, Scheurer ME.

Published In: Cancer Causes Control. 2023 Jul 8. doi: 10.1007/s10552-023-01746-3. Epub 2023 Jul 8. PMID: 37421504.

Summary: Following up on its previous work, which demonstrated reduced risk of leukemia for breastfed compared to formula-fed children, CLIC investigated whether infant feeding practices were associated with childhood brain tumors. This study found no evidence that breastfeeding reduced risk of all childhood brain tumors collectively, or the most common subtypes (astrocytoma, ependymoma, medulloblastoma and PNET) specifically

Parental occupational exposure to combustion products, metals, silica and asbestos and risk of childhood leukaemia: Findings from the Childhood Cancer and Leukaemia International Consortium (CLIC)

Authors: Onyije FM, Olsson A, Erdmann F, Magnani C, Petridou E, Clavel J, Miligi L, Bonaventure A, Ferrante D, Piro S, Peters S, Vermeulen R, Kromhout H, Schüz J; NARECHEM-ST Group.

Published In: Environ Int. 2022 Sep;167:107409. doi: 10.1016/j.envint.2022.107409. Epub 2022 Jul 20. PMID: 35908390.

Summary: CLIC’s analysis suggested that children of fathers who were exposed to high levels of crystalline silica around the time of conception had increased risk of ALL and AML.

Infant feeding practices and childhood acute leukemia: findings from the Childhood Cancer & Leukemia International Consortium.

Authors: Schraw JM, Bailey HD, Bonaventure A, Mora AM, Roman E, Mueller BA, Clavel J, Petridou ET, Karalexi M, Ntzani E, Ezzat S, Rashed WM, Marcotte EL, Spector LG, Metayer C, Kang AY, Magnani C, Miligi L, Dockerty JD, Mejίa-Aranguré JM, Nuñez Enriquez JC, Infante-Rivard C, Milne E, Scheurer ME.

Published In: Int J Cancer. 2022 Oct. 1;151(7):1013-1023. doi: 10.1002/ijc.34062. Epub 2022 Jun 24. PMID: 35532209.

Summary: CLIC found that children who were breastfed for at least four months had a lower risk of ALL and AML. This association may be stronger for children who are exclusively breastfed.

Age-, sex- and disease subtype-related foetal growth differentials in childhood acute myeloid leukaemia risk: A Childhood Leukemia International Consortium analysis.

Authors: Karalexi MA, Dessypris N, Ma X, Spector LG, Marcotte E, Clavel J, Pombo-de-Oliveira MS, Heck JE, Roman E, Mueller BA, Hansen J, Auvinen A, Lee PC, Schüz J, Magnani C, Mora AM, Dockerty JD, Scheurer ME, Wang R, Bonaventure A, Kane E, Doody DR; NARECHEM-ST Group; FRECCLE Group, Erdmann F, Kang AY, Metayer C, Milne E, Petridou ET.

Published In: Eur J Cancer. 2020 May;130:1-11. doi: 10.1016/j.ejca.2020.01.018. Epub 2020 Mar 9. PMID: 32163883.

Summary: CLIC found that bigger babies or those with faster growth before birth had a higher risk of AML in childhood. The risk was greatest in infant boys and for certain subtypes of the disease.

Coffee and tea consumption during pregnancy and risk of childhood acute myeloid leukemia: A Childhood Leukemia International Consortium (CLIC) study.

Authors: Karalexi MA, Dessypris N, Clavel J, Metayer C, Erdmann F, Orsi L, Kang AY, Schüz J, Bonaventure A, Greenop KR, Milne E, Petridou ET; NARECHEM-ST Group.

Published In: Cancer Epidemiol. 2019 Oct;62:101581. doi: 10.1016/j.canep.2019.101581. Epub 2019 Aug 12. PMID: 31416015.

Summary: CLIC’s analysis suggested an increased risk of AML among children of mothers who drank more than one cup of coffee per day during pregnancy.

Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring: findings from the Childhood Leukaemia International Consortium (CLIC)

Authors: Talibov M, Olsson A, Bailey H, Erdmann F, Metayer C, Magnani C, Petridou E, Auvinen A, Spector L, Clavel J, Roman E, Dockerty J, Nikkilä A, Lohi O, Kang A, Psaltopoulou T, Miligi L, Vila J, Cardis E, Schüz J.

Published In: Occup Environ Med. 2019 Oct;76(10):746-753. doi: 10.1136/oemed-2019-105706. Epub 2019 Jul 29. PMID: 31358566; PMCID: PMC6817988.

Summary: CLIC found no association between parents’ exposures to extremely low-frequency magnetic fields in their jobs and an increased risk of ALL or AML.

Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome.

Authors: Brown AL, de Smith AJ, Gant VU, Yang W, Scheurer ME, Walsh KM, Chernus JM, Kallsen NA, Peyton SA, Davies GE, Ehli EA, Winick N, Heerema NA, Carroll AJ, Borowitz MJ, Wood BL, Carroll WL, Raetz EA, Feingold E, Devidas M, Barcellos LF, Hansen HM, Morimoto L, Kang AY, Smirnov I, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson P, Spector LG, Pombo-de-Oliveira MS, DeWan AT, Mullighan CG, Hunger SP, Pui CH, Loh ML, Zwick ME, Metayer C, Ma X, Mueller BA, Sherman SL, Wiemels JL, Relling MV, Yang JJ, Lupo PJ, Rabin KR.

Published In: Blood. 2019 Oct 10;134(15):1227-1237. doi: 10.1182/blood.2018890764. Epub 2019 Jul 26. PMID: 31350265; PMCID: PMC6788009 [Available on 2020-10-10].

Summary: CLIC found that the same genetic variants associated with ALL in children without Down syndrome operate more strongly in children with ALL and Down syndrome.

Heritable variation at the chromosome 21 gene ERG is associated with acute lymphoblastic leukemia risk in children with and without Down syndrome.

Authors: de Smith AJ, Walsh KM, Morimoto LM, Francis SS, Hansen HM, Jeon S, Gonseth S, Chen M, Sun H, Luna-Fineman S, Antillón F, Girón V, Kang AY, Smirnov I, Shao X, Whitehead TP, Barcellos LF, Jolly KW, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson PD, Pombo-de-Oliveira MS, Spector LG, DeWan AT, Mueller BA, Chiang C, Metayer C, Ma X, Wiemels JL.

Published In: Leukemia. 2019 Nov;33(11):2746-2751. doi: 10.1038/s41375-019-0514-9. Epub 2019 Jul 11. PMID: 31296947; PMCID: PMC6858994 [Available on 2020-11-01].

Summary: CLIC ‘s analysis showed that variants in the ERG gene are associated with ALL in Latino children both with and without Down syndrome.

Parental age and the risk of childhood acute myeloid leukemia: results from the Childhood Leukemia International Consortium

Authors: Panagopoulou P, Skalkidou A, Marcotte E, Erdmann F, Ma X, Heck JE, Auvinen A, Mueller BA, Spector LG, Roman E, Metayer C, Magnani C, Pombo-de-Oliveira MS, Scheurer ME, Mora AM, Dockerty JD, Hansen J, Kang AY, Wang R, Doody DR, Kane E, Schüz J, Christodoulakis C, Ntzani E, Petridou ET; FRECCLE Group; NARECHEM-ST Group.

Published In: Cancer Epidemiol. 2019 Apr;59:158-165. doi: 10.1016/j.canep.2019.01.022. Epub 2019 Feb 15. PMID: 30776582; PMCID: PMC7098424.

Summary: CLIC found a substantial increase in risk of AML in infants whose mothers were 40 years of age or older when their child was born.

Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium

Authors: Petridou ET, Georgakis MK, Erdmann F, Ma X, Heck JE, Auvinen A, Mueller BA, Spector LG, Roman E, Metayer C, Magnani C, Pombo-de-Oliveira MS, Ezzat S, Scheurer ME, Mora AM, Dockerty JD, Hansen J, Kang AY, Wang R, Doody DR, Kane E, Rashed WM, Dessypris N, Schüz J, Infante-Rivard C, Skalkidou A.

Published In: Eur J Epidemiol. 2018 Oct; 33(10):965-976. doi: 10.1007/s10654-018-0402-z. Epub 2018 May 14. PMID: 29761423; PMCID: PMC6384148.

Summary: CLIC observed that the risk of childhood ALL increased slightly when both parents were 35 years or older at the time of birth of their child.

Living on a farm, contact with farm animals and pets, and childhood acute lymphoblastic leukemia: pooled and meta-analyses from the Childhood Leukemia International Consortium

Authors: Orsi L, Magnani C, Petridou ET, Dockerty JD, Metayer C, Milne E, Bailey HD, Dessypris N, Kang AY, Wesseling C, Infante-Rivard C, Wünsch-Filho V, Mora AM, Spector LG, Clavel J.

Published In: Cancer Med. 2018 Jun;7(6):2665-2681. doi: 10.1002/cam4.1466. Epub 2018 Apr 16. PMID: 29663688; PMCID: PMC6010788.

Summary: CLIC’s analysis revealed that regular contact with livestock (cattle, pigs, and sheep) or pets (cats and dogs) in the first year of life decreased the risk of later childhood ALL.

Maternal consumption of coffee and tea during pregnancy and risk of childhood ALL: a pooled analysis from the childhood Leukemia International Consortium

Authors: Milne E, Greenop KR, Petridou E, Bailey HD, Orsi L, Kang AY, Baka M, Bonaventure A, Kourti M, Metayer C, Clavel J.

Published In: Cancer Causes Control. 2018 Jun;29(6):539-550. doi: 10.1007/s10552-018-1024-1. Epub 2018 Mar 29. PMID: 29600472.

Summary: CLIC determined that children of mothers who drank more than 2 cups of coffee per day while pregnant had a slightly increased risk of ALL.

Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium

Authors: Metayer C, Petridou E, Aranguré JM, Roman E, Schüz J, Magnani C, Mora AM, Mueller BA, de Oliveira MS, Dockerty JD, McCauley K, Lightfoot T, Hatzipantelis E, Rudant J, Flores-Lujano J, Kaatsch P, Miligi L, Wesseling C, Doody DR, Moschovi M; MIGICCL Group, Orsi L, Mattioli S, Selvin S, Kang AY, Clavel J.

Published In: Am J Epidemiol. 2016 Aug 15;184(4):261-73. doi: 10.1093/aje/kww018. Epub 2016 Aug 3. PMID: 27492895; PMCID: PMC4983653.

Summary: CLIC found that children with fathers who smoke had an increased risk of AML, with the highest risks associated with heavy smokers.

Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

Authors: Marcotte EL, Thomopoulos TP, Infante-Rivard C, Clavel J, Petridou ET, Schüz J, Ezzat S, Dockerty JD, Metayer C, Magnani C, Scheurer ME, Mueller BA, Mora AM, Wesseling C, Skalkidou A, Rashed WM, Francis SS, Ajrouche R, Erdmann F, Orsi L, Spector LG.

Published In: Lancet Haematol. 2016 Apr;3(4):e176-85. doi: 10.1016/S2352-3026(16)00002-8. Epub 2016 Feb 27. Erratum in: Lancet Haematol. 2016 Apr;3(4):e162. PMID: 27063976; PMCID: PMC5283076.

Summary: CLIC observed a slightly increased risk of ALL among children delivered by Caesarean section before labor had begun.

Home paint exposures and risk of childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium

Authors: Bailey HD, Metayer C, Milne E, Petridou ET, Infante-Rivard C, Spector LG, Clavel J, Dockerty JD, Zhang L, Armstrong BK, Rudant J, Fritschi L, Amigou A, Hatzipantelis E, Kang AY, Stiakaki E, Schüz J.

Published In: Cancer Causes Control. 2015 Sep;26(9):1257-70. doi: 10.1007/s10552-015-0618-0. Epub 2015 Jul 2. PMID: 26134047; PMCID: PMC5257283.

Summary: CLIC’s analysis showed that home paint exposure shortly before conception, during pregnancy, and after birth slightly increased the risk of childhood ALL.

Home pesticide exposures and risk of childhood leukemia: Findings from the childhood leukemia international consortium

Authors: Bailey HD, Infante-Rivard C, Metayer C, Clavel J, Lightfoot T, Kaatsch P, Roman E, Magnani C, Spector LG, Th Petridou E, Milne E, Dockerty JD, Miligi L, Armstrong BK, Rudant J, Fritschi L, Simpson J, Zhang L, Rondelli R, Baka M, Orsi L, Moschovi M, Kang AY, Schüz J.

Published In: Int J Cancer. 2015 Dec 1;137(11):2644-63. doi: 10.1002/ijc.29631. Epub 2015 Jun 26. PMID: 26061779; PMCID: PMC4572913.

Summary: CLIC found that home pesticide exposure before birth was associated with a moderately elevated risk for childhood ALL and AML.

Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a Childhood Leukemia International Consortium study

Authors: Rudant J, Lightfoot T, Urayama KY, Petridou E, Dockerty JD, Magnani C, Milne E, Spector LG, Ashton LJ, Dessypris N, Kang AY, Miller M, Rondelli R, Simpson J, Stiakaki E, Orsi L, Roman E, Metayer C, Infante-Rivard C, Clavel J.

Published In: Am J Epidemiol. 2015 Apr 15;181(8):549-62. doi: 10.1093/aje/kwu298. Epub 2015 Mar 1. PMID: 25731888; PMCID: PMC4850899.

Summary: CLIC determined that early day care attendance as well as breastfeeding for over 6 months reduced the risk of childhood ALL.

Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood Leukemia International Consortium study

Authors: Metayer C, Milne E, Dockerty JD, Clavel J, Pombo-de-Oliveira MS, Wesseling C, Spector LG, Schüz J, Petridou E, Ezzat S, Armstrong BK, Rudant J, Koifman S, Kaatsch P, Moschovi M, Rashed WM, Selvin S, McCauley K, Hung RJ, Kang AY, Infante-Rivard C.

Published In: Epidemiology. 2014 Nov;25(6):811-22. doi: 10.1097/EDE.0000000000000141. PMID: 25207954; PMCID: PMC5903563.

Summary: CLIC’s analysis revealed that children of mothers who took folic acid and other vitamins before birth had a decreased risk of ALL and AML.

Parental occupational paint exposure and risk of childhood leukemia in the offspring: findings from the Childhood Leukemia International Consortium

Authors: Bailey HD, Fritschi L, Metayer C, Infante-Rivard C, Magnani C, Petridou E, Roman E, Spector LG, Kaatsch P, Clavel J, Milne E, Dockerty JD, Glass DC, Lightfoot T, Miligi L, Rudant J, Baka M, Rondelli R, Amigou A, Simpson J, Kang AY, Moschovi M, Schüz J.

Published In: Cancer Causes Control. 2014 Oct;25(10):1351-67. doi: 10.1007/s10552-014-0441-z. Epub 2014 Aug 5. PMID: 25088805; PMCID: PMC4845093.

Summary: CLIC did not find any evidence that mothers’ or fathers’ exposures to paints at work increased the risk of ALL or AML among their children.

Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: findings from the childhood leukemia international consortium

Authors: Bailey HD, Fritschi L, Infante-Rivard C, Glass DC, Miligi L, Dockerty JD, Lightfoot T, Clavel J, Roman E, Spector LG, Kaatsch P, Metayer C, Magnani C, Milne E, Polychronopoulou S, Simpson J, Rudant J, Sidi V, Rondelli R, Orsi L, Kang AY, Petridou E, Schüz J.

Published In: Int J Cancer. 2014 Nov 1;135(9):2157-72. doi: 10.1002/ijc.28854. Epub 2014 Apr 4. PMID: 24700406; PMCID: PMC4845098.

Summary: CLIC found that children of fathers who worked with pesticides around the time of conception had a slightly increased risk of ALL, while children of mothers who worked with pesticides during pregnancy had a markedly increased risk of AML.

Fetal growth and childhood acute lymphoblastic leukemia: findings from the childhood leukemia international consortium

Authors: Milne E, Greenop KR, Metayer C, Schüz J, Petridou E, Pombo-de-Oliveira MS, Infante-Rivard C, Roman E, Dockerty JD, Spector LG, Koifman S, Orsi L, Rudant J, Dessypris N, Simpson J, Lightfoot T, Kaatsch P, Baka M, Faro A, Armstrong BK, Clavel J, Buffler PA.

Published In: Int J Cancer. 2013 Dec 15;133(12):2968-79. doi: 10.1002/ijc.28314. Epub 2013 Aug 1. PMID: 23754574; PMCID: PMC3797193.

Summary: CLIC observed that children who had higher than expected birth weights, after taking into account length of pregnancy, had a modestly increased risk of ALL.

The Childhood Leukemia International Consortium

Authors: Metayer C, Milne E, Clavel J, Infante-Rivard C, Petridou E, Taylor M, Schüz J, Spector LG, Dockerty JD, Magnani C, Pombo-de-Oliveira MS, Sinnett D, Murphy M, Roman E, Monge P, Ezzat S, Mueller BA, Scheurer ME, Armstrong BK, Birch J, Kaatsch P, Koifman S, Lightfoot T, Bhatti P, Bondy ML, Rudant J, O’Neill K, Miligi L, Dessypris N, Kang AY, Buffler PA

Published In: Cancer Epidemiol. 2013 Jun;37(3):336-47. doi: 10.1016/j.canep.2012.12.011. Epub 2013 Feb 9. PMID: 23403126; PMCID: PMC3652629.

Summary: This manuscript described CLIC, including its purpose, methods, and membership at the time.