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Cancer Causes & Control
Published in: Cancer Causes & Control 12/2011

Open Access 01-12-2011 | Original paper

Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia

Authors: Anand P. Chokkalingam, Karen Bartley, Joseph L. Wiemels, Catherine Metayer, Lisa F. Barcellos, Helen M. Hansen, Melinda C. Aldrich, Neela Guha, Kevin Y. Urayama, Ghislaine Scélo, Jeffrey S. Chang, Stacy R. Month, John K. Wiencke, Patricia A. Buffler

Published in: Cancer Causes & Control | Issue 12/2011

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Abstract

Background

Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes.

Methods

We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995–2002.

Results

We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL.

Conclusions

These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis.
Appendix
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Metadata
Title
Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia
Authors
Anand P. Chokkalingam
Karen Bartley
Joseph L. Wiemels
Catherine Metayer
Lisa F. Barcellos
Helen M. Hansen
Melinda C. Aldrich
Neela Guha
Kevin Y. Urayama
Ghislaine Scélo
Jeffrey S. Chang
Stacy R. Month
John K. Wiencke
Patricia A. Buffler
Publication date
01-12-2011
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 12/2011
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-011-9848-y

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