caa a22 4500 445315202 CHVBK 20180317142644.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10552-011-9848-y doi (NATIONALLICENCE)springer-10.1007/s10552-011-9848-y Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia [Elektronische Daten] [Anand Chokkalingam, Karen Bartley, Joseph Wiemels, Catherine Metayer, Lisa Barcellos, Helen Hansen, Melinda Aldrich, Neela Guha, Kevin Urayama, Ghislaine Scélo, Jeffrey Chang, Stacy Month, John Wiencke, Patricia Buffler] 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. The Author(s), 2011 Leukemia nationallicence Childhood cancer nationallicence DNA repair nationallicence Genetic susceptibility nationallicence Chokkalingam Anand Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut Bartley Karen Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut Wiemels Joseph Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA aut Metayer Catherine Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut Barcellos Lisa Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut Hansen Helen Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA aut Aldrich Melinda Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA aut Guha Neela International Agency for Research on Cancer, Lyon, France aut Urayama Kevin International Agency for Research on Cancer, Lyon, France aut Scélo Ghislaine International Agency for Research on Cancer, Lyon, France aut Chang Jeffrey National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan aut Month Stacy Kaiser Permanente Medical Group, Oakland, CA, USA aut Wiencke John Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA aut Buffler Patricia Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut Cancer Causes & Control Springer Netherlands 22/12(2011-12-01), 1721-1730 0957-5243 22:12<1721 2011 22 10552 https://doi.org/10.1007/s10552-011-9848-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10552-011-9848-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chokkalingam Anand Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut NATIONALLICENCE 700 1- Bartley Karen Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut NATIONALLICENCE 700 1- Wiemels Joseph Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Metayer Catherine Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut NATIONALLICENCE 700 1- Barcellos Lisa Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut NATIONALLICENCE 700 1- Hansen Helen Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Aldrich Melinda Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA aut NATIONALLICENCE 700 1- Guha Neela International Agency for Research on Cancer, Lyon, France aut NATIONALLICENCE 700 1- Urayama Kevin International Agency for Research on Cancer, Lyon, France aut NATIONALLICENCE 700 1- Scélo Ghislaine International Agency for Research on Cancer, Lyon, France aut NATIONALLICENCE 700 1- Chang Jeffrey National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan aut NATIONALLICENCE 700 1- Month Stacy Kaiser Permanente Medical Group, Oakland, CA, USA aut NATIONALLICENCE 700 1- Wiencke John Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Buffler Patricia Division of Epidemiology, School of Public Health, University of California Berkeley, 1995 University Avenue, Suite 460, 94704, Berkeley, CA, USA aut NATIONALLICENCE 773 0- Cancer Causes & Control Springer Netherlands 22/12(2011-12-01), 1721-1730 0957-5243 22:12<1721 2011 22 10552 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer