title: International study of factors affecting human chromosome translocations.
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.
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sigurdson
authors.forename: Mina
authors.initials: M
authors.lastname: Ha
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
authors.forename: Parveen
authors.initials: P
authors.lastname: Bhatti
authors.forename: Radim J
authors.initials: RJ
authors.lastname: Sram
authors.forename: Olena
authors.initials: O
authors.lastname: Beskid
authors.forename: E Janet
authors.initials: EJ
authors.lastname: Tawn
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Whitehouse
authors.forename: Carita
authors.initials: C
authors.lastname: Lindholm
authors.forename: Mimako
authors.initials: M
authors.lastname: Nakano
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kodama
authors.forename: Nori
authors.initials: N
authors.lastname: Nakamura
authors.forename: Irena
authors.initials: I
authors.lastname: Vorobtsova
authors.forename: Ursula
authors.initials: U
authors.lastname: Oestreicher
authors.forename: Günther
authors.initials: G
authors.lastname: Stephan
authors.forename: Lee C
authors.initials: LC
authors.lastname: Yong
authors.forename: Manfred
authors.initials: M
authors.lastname: Bauchinger
authors.forename: Ernst
authors.initials: E
authors.lastname: Schmid
authors.forename: Hai Won
authors.initials: HW
authors.lastname: Chung
authors.forename: Firouz
authors.initials: F
authors.lastname: Darroudi
authors.forename: Laurence
authors.initials: L
authors.lastname: Roy
authors.forename: Phillipe
authors.initials: P
authors.lastname: Voisin
authors.forename: Joan F
authors.initials: JF
authors.lastname: Barquinero
authors.forename: Gordon
authors.initials: G
authors.lastname: Livingston
authors.forename: David
authors.initials: D
authors.lastname: Blakey
authors.forename: Isamu
authors.initials: I
authors.lastname: Hayata
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.forename: L Michelle
authors.initials: LM
authors.lastname: Bennett
authors.forename: L Gayle
authors.initials: LG
authors.lastname: Littlefield
authors.forename: Alan A
authors.initials: AA
authors.lastname: Edwards
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Kleinerman
authors.forename: James D
authors.initials: JD
authors.lastname: Tucker
mesh_terms: 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