Chromosomal aberrations and SCEs as biomarkers of cancer risk.
Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.
Norppa
H
H
New Technologies and Risks, Finnish Institute of Occupational Health, FI-00250 Helsinki, Finland. hannu.norppa@ttl.fi <hannu.norppa@ttl.fi>
Bonassi
S
S
Hansteen
I-L
IL
Hagmar
L
L
Strömberg
U
U
Rössner
P
P
Boffetta
P
P
Lindholm
C
C
Gundy
S
S
Lazutka
J
J
Cebulska-Wasilewska
A
A
Fabiánová
E
E
Srám
R J
RJ
Knudsen
L E
LE
Barale
R
R
Fucic
A
A
D002869:Chromosome Aberrations; D015331:Cohort Studies; D005060:Europe; D005819:Genetic Markers; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012854:Sister Chromatid Exchange; D015262:Xenobiotics / Q000378:metabolism
D005819:Genetic Markers; D015262:Xenobiotics