Maternal diet and infant leukemia: The DNA topoisomerase II inhibitor hypothesis: A report from the Children's Oncology Group

Logan G. Spector, Yang Xie, Leslie L. Robison, Nyla A. Heerema, Joanne M. Hilden, Beverly Lange, Carolyn A. Felix, Stella M. Davies, Joanne Slavin, John D. Potter, Cindy K. Blair, Gregory H. Reaman, Julie A. Ross

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Background: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). Methods: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. Results: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). Conclusion: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.

Original languageEnglish (US)
Pages (from-to)651-655
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number3
DOIs
StatePublished - Mar 2005

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Topoisomerase II Inhibitors
Leukemia
Mothers
Acute Myeloid Leukemia
Diet
Vegetables
Fruit
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Food
Pregnancy
Case-Control Studies
Logistic Models
Odds Ratio
Confidence Intervals
Drug Therapy

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Maternal diet and infant leukemia : The DNA topoisomerase II inhibitor hypothesis: A report from the Children's Oncology Group. / Spector, Logan G.; Xie, Yang; Robison, Leslie L.; Heerema, Nyla A.; Hilden, Joanne M.; Lange, Beverly; Felix, Carolyn A.; Davies, Stella M.; Slavin, Joanne; Potter, John D.; Blair, Cindy K.; Reaman, Gregory H.; Ross, Julie A.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 14, No. 3, 03.2005, p. 651-655.

Research output: Contribution to journalArticle

Spector, LG, Xie, Y, Robison, LL, Heerema, NA, Hilden, JM, Lange, B, Felix, CA, Davies, SM, Slavin, J, Potter, JD, Blair, CK, Reaman, GH & Ross, JA 2005, 'Maternal diet and infant leukemia: The DNA topoisomerase II inhibitor hypothesis: A report from the Children's Oncology Group', Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 3, pp. 651-655. https://doi.org/10.1158/1055-9965.EPI-04-0602
Spector, Logan G. ; Xie, Yang ; Robison, Leslie L. ; Heerema, Nyla A. ; Hilden, Joanne M. ; Lange, Beverly ; Felix, Carolyn A. ; Davies, Stella M. ; Slavin, Joanne ; Potter, John D. ; Blair, Cindy K. ; Reaman, Gregory H. ; Ross, Julie A. / Maternal diet and infant leukemia : The DNA topoisomerase II inhibitor hypothesis: A report from the Children's Oncology Group. In: Cancer Epidemiology Biomarkers and Prevention. 2005 ; Vol. 14, No. 3. pp. 651-655.
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abstract = "Background: The MLL 11q23 translocation arises in utero and is present in 75{\%} of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). Methods: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. Results: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95{\%} confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). Conclusion: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.",
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T2 - The DNA topoisomerase II inhibitor hypothesis: A report from the Children's Oncology Group

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AU - Xie, Yang

AU - Robison, Leslie L.

AU - Heerema, Nyla A.

AU - Hilden, Joanne M.

AU - Lange, Beverly

AU - Felix, Carolyn A.

AU - Davies, Stella M.

AU - Slavin, Joanne

AU - Potter, John D.

AU - Blair, Cindy K.

AU - Reaman, Gregory H.

AU - Ross, Julie A.

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N2 - Background: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). Methods: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. Results: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). Conclusion: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.

AB - Background: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). Methods: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. Results: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). Conclusion: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.

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