Impact of types of lymphocyte chromosomal aberrations on human cancer risk: results from Nordic and Italian cohorts

TY - JOUR

T1 - Impact of types of lymphocyte chromosomal aberrations on human cancer risk

T2 - results from Nordic and Italian cohorts

AU - Hagmar, Lars

AU - Strömberg, Ulf

AU - Bonassi, Stefano

AU - Hansteen, Inger-Lise

AU - Knudsen, Lisbeth E.

AU - Lindholm, Carita

AU - Norppa, Hannu

PY - 2004/3/15

Y1 - 2004/3/15

N2 - 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.

AB - 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.

KW - Chromatids

KW - Chromosome Aberrations

KW - Chromosomes, Human

KW - Cohort Studies

KW - Finland

KW - Follow-Up Studies

KW - Genetic Markers

KW - Humans

KW - Italy

KW - Lymphocytes

KW - Neoplasms

KW - Norway

KW - Risk Factors

KW - Scandinavian and Nordic Countries

KW - Sister Chromatid Exchange

KW - Survival Rate

KW - Sweden

M3 - Journal article

C2 - 15026371

SN - 0008-5472

VL - 64

SP - 2258

EP - 2263

JO - Cancer Research

JF - Cancer Research

IS - 6

ER -