International study of factors affecting human chromosome translocations

Alice J. Sigurdson, Mina Ha, Michael Hauptmann, Parveen Bhatti, Radim J. Sram, Olena Beskid, E. Janet Tawn, Caroline A. Whitehouse, Carita Lindholm, Mimako Nakano, Yoshiaki Kodama, Nori Nakamura, Irena Vorobtsova, Ursula Oestreicher, Günther Stephan, Lee C. Yong, Manfred Bauchinger, Ernst Schmid, Hai Won Chung, Firouz DarroudiLaurence Roy, Phillipe Voisin, Joan F. Barquinero, Gordon Livingston, David Blakey, Isamu Hayata, Wei Zhang, Chunyan Wang, L. Michelle Bennett, L. Gayle Littlefield, Alan Edwards, Ruth A. Kleinerman, James D. Tucker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)

Abstract

Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p < 0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p < 0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.

Original languageEnglish
Pages (from-to)112-121
Number of pages10
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume652
Issue number2
DOIs
Publication statusPublished - 30 Apr 2008

Bibliographical note

Funding Information:
This research was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, the National Cancer Institute (NCI), NIH, DHHS and by an Intra-agency agreement between the National Institute of Allergy and Infectious Diseases (NIAID) and the NCI, NIAID agreement #Y2-A1-5077 and #Y3-CO-5117; performed in part under the auspices of the US Department of Energy by the Lawrence Livermore National Laboratory from contract No. W-7405-ENG-48; CEC Concerted Action (FIGD-CT-200-20040; a grant from the Czech Ministry of Environment VaV/340/2/00, VaV/740/5/03 and VaV-SL/5/160/05; The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan, is a private, non-profit foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE), the latter through the National Academy of Sciences, the present publication was supported by RERF Research Protocol RP 8-93; The Spanish Nuclear Safety Council (ref 246/96); The European Union SOUL project (FIP6R-516478); a grant from the Russian Foundation for Basic Research, 01-0449118; British Nuclear Fuels plc, United Kingdom; an interagency agreement between the NCI and the National Institute for Occupational Safety and Health, Y1-CP-9012. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

Keywords

  • Background frequency
  • Chromosome translocations
  • Controls
  • Fluorescence in situ hybridization

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