International study of factors affecting human chromosome translocations
Résumé
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. © 2008 Elsevier B.V. All rights reserved.
Mots clés
confidence interval
controlled study
Europe
female
fluorescence in situ hybridization
gender
human
infant
linear regression analysis
major clinical study
male
mutation rate
newborn
North America
peripheral lymphocyte
Poisson distribution
priority journal
umbilical cord blood
Adolescent
Adult
Age Factors
Aged
80 and over
Child
Preschool
Chromosome Painting
Ethnic Groups
Female
Humans
In Situ Hybridization
Fluorescence
Infant
Newborn
International Cooperation
Male
Middle Aged
Risk Factors
Sex Factors
Smoking
Translocation
Genetic
adolescent
adult
aged
aging
article
Asia
child
chromosome damage
chromosome painting
chromosome translocation
cigarette smoking