The study of rare cancers has led to major findings in cancer etiology. Infants with leukemia may represent another such rare group. Infants with leukemia are clinically, epidemiologically, and biologically distinct from older children with leukemia. Approximately 60% of infants with acute myeloid leukemia (AML) and 75% of infants with acute lymphoblastic leukemia (ALL) present with an MLL gene rearrangement in their leukemia cells. Molecular studies demonstrate that infant leukemia's arise in utero. Our preliminary data indicate that maternal exposure to environmental agents, including DNA topoisomerase II inhibitors, are important in the etiology of infant leukemia. Further, others and we have evidence to suggest that the etiology of MLL positive infant leukemia is distinctly different from MLL negative infant leukemia. We are uniquely positioned to expand our current study to increase the statistical power to evaluate associations between MLL positive and MLL negative infant leukemia. Further, we can collect DNA retrospectively and prospectively from both mothers and infants to investigate the role of specific genetic polymorphisms in the etiology of infant leukemia.
Our specific aims are to: a) interview an additional 240 mothers of infant cases (bringing the case total to 484) to increase the statistical power and make this the largest study to ask whether specific chemicals are associated with MLL infant leukemia; b) obtain DNA from infant cases to investigate genetic polymorphisms (including NQ01, MTHFR, GSTM1, GSTT1, GSTPi, MPO, COMT, IGF1) associated with infant leukemia; c) obtain DNA from case mothers and investigate the genetic polymorphisms described above in association with infant leukemia; and d) explore gene-environment interactions in the etiology of MLL infant leukemia. We hypothesize that specific exposure, including those associated with DNA Topoisomerase II inhibition, are more often associated with MLL-positive infant leukemia. Further, we hypothesize that genetic differences in the ability to detoxify environmental toxins contributes to genetic susceptibility to MLL-positive leukemia. Finally, we hypothesize that unfavorable genotypes, in combination with exposure to specific agents, increases the risk of MLL infant leukemia. This study will utilize the unique resources available through the Children's Oncology Group, and include ascertainment of cases over a four-year period (Jan 1, 2003-Dec 31, 2006).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA079940-08
Application #
7217904
Study Section
Special Emphasis Panel (ZRG1-SNEM-5 (02))
Program Officer
Kasten-Sportes, Carol H
Project Start
1999-02-09
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2009-03-31
Support Year
8
Fiscal Year
2007
Total Cost
$304,027
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Marcotte, Erin L; Richardson, Michaela R; Roesler, Michelle A et al. (2018) Cesarean Delivery and Risk of Infant Leukemia: A Report from the Children's Oncology Group. Cancer Epidemiol Biomarkers Prev 27:473-478
Valentine, M C; Linabery, A M; Chasnoff, S et al. (2014) Excess congenital non-synonymous variation in leukemia-associated genes in MLL- infant leukemia: a Children's Oncology Group report. Leukemia 28:1235-41
Poynter, Jenny N; Ross, Julie A; Hooten, Anthony J et al. (2013) Predictors of mother and child DNA yields in buccal cell samples collected in pediatric cancer epidemiologic studies: a report from the Children's Oncology group. BMC Genet 14:69
Ross, Julie A; Linabery, Amy M; Blommer, Crystal N et al. (2013) Genetic variants modify susceptibility to leukemia in infants: a Children's Oncology Group report. Pediatr Blood Cancer 60:31-4
Sam, Thien N; Kersey, John H; Linabery, Amy M et al. (2012) MLL gene rearrangements in infant leukemia vary with age at diagnosis and selected demographic factors: a Children's Oncology Group (COG) study. Pediatr Blood Cancer 58:836-9
Ognjanovic, S; Blair, C; Spector, L G et al. (2011) Analgesic use during pregnancy and risk of infant leukaemia: a Children's Oncology Group study. Br J Cancer 104:532-6
Slater, Megan E; Linabery, Amy M; Blair, Cindy K et al. (2011) Maternal prenatal cigarette, alcohol and illicit drug use and risk of infant leukaemia: a report from the Children's Oncology Group. Paediatr Perinat Epidemiol 25:559-65
Slater, Megan E; Linabery, Amy M; Spector, Logan G et al. (2011) Maternal exposure to household chemicals and risk of infant leukemia: a report from the Children's Oncology Group. Cancer Causes Control 22:1197-204
Jurek, Anne M; Greenland, Sander; Spector, Logan G et al. (2011) Self-report versus medical record - perinatal factors in a study of infant leukaemia: a study from the Children's Oncology Group. Paediatr Perinat Epidemiol 25:540-8
Puumala, Susan E; Spector, Logan G; Wall, Melanie M et al. (2010) Infant leukemia and parental infertility or its treatment: a Children's Oncology Group report. Hum Reprod 25:1561-8

Showing the most recent 10 out of 25 publications