International study of factors affecting human chromosome translocations.
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.
Sigurdson
Alice J
AJ
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Ha
Mina
M
Hauptmann
Michael
M
Bhatti
Parveen
P
Sram
Radim J
RJ
Beskid
Olena
O
Tawn
E Janet
EJ
Whitehouse
Caroline A
CA
Lindholm
Carita
C
Nakano
Mimako
M
Kodama
Yoshiaki
Y
Nakamura
Nori
N
Vorobtsova
Irena
I
Oestreicher
Ursula
U
Stephan
Günther
G
Yong
Lee C
LC
Bauchinger
Manfred
M
Schmid
Ernst
E
Chung
Hai Won
HW
Darroudi
Firouz
F
Roy
Laurence
L
Voisin
Phillipe
P
Barquinero
Joan F
JF
Livingston
Gordon
G
Blakey
David
D
Hayata
Isamu
I
Zhang
Wei
W
Wang
Chunyan
C
Bennett
L Michelle
LM
Littlefield
L Gayle
LG
Edwards
Alan A
AA
Kleinerman
Ruth A
RA
Tucker
James D
JD
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001208:Asia; D002648:Child; D002675:Child, Preschool; D020223:Chromosome Painting; D005006:Ethnicity; D005060:Europe; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D009656:North America; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D014178:Translocation, Genetic