Impact of types of lymphocyte chromosomal aberrations on human cancer risk: results from Nordic and Italian cohorts.
The frequency of cells with structural chromosomal aberrations (CAs) in peripheral blood lymphocytes is the first genotoxicity biomarker that has shown an association with cancer risk. CAs are usually divided into chromosome-type (CSAs) and chromatid-type aberrations (CTAs), with different mechanisms of formation. From a mechanistic point of view, it is of interest to clarify whether the cancer predictivity of CAs is different with respect to CSAs and CTAs. We report here cancer risk for cytogenetically tested, healthy subjects with respect to frequency of CAs, CSAs, and CTAs in peripheral blood lymphocytes, using Nordic (1981 subjects with CA data, 1871 subjects with CSA/CTA data) and Italian (1573 subjects with CA data, 877 subjects with CTA/CSA data) cohorts, with a median follow-up of 17 years. High levels of CAs at test were clearly associated with increased total cancer incidence in the Nordic cohorts and increased total cancer mortality in the Italian cohort. In the Nordic cohorts, significantly elevated cancer risks were observed for subjects with both high CSAs and high CTAs at test, and these variables showed equally strong cancer predictivity. The results of the Italian cohort did not indicate any clear-cut difference in cancer predictivity between the CSA and CTA biomarkers. There was no significant effect modification by age at test, gender, country, or time since test. The results suggest that both DNA double-strand breaks and other initial DNA lesions responsible for CSAs and CTAs are associated with cancer risk.
Hagmar
Lars
L
Department of Occupational and Environmental Medicine, Lund University Hospital, SE-221 85 Lund, Sweden. lars.hagmar@ymed.lu.se
Strömberg
Ulf
U
Bonassi
Stefano
S
Hansteen
Inger-Lise
IL
Knudsen
Lisbeth Ehlert
LE
Lindholm
Carita
C
Norppa
Hannu
H
D002842:Chromatids; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D015331:Cohort Studies; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008214:Lymphocytes; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D009664:Norway / Q000453:epidemiology; D012307:Risk Factors; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D012854:Sister Chromatid Exchange; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology
D005819:Genetic Markers