Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

TY - JOUR

T1 - Chromosomal aberration frequency in lymphocytes predicts the risk of cancer

T2 - results from a pooled cohort study of 22 358 subjects in 11 countries

AU - Bonassi, Stefano

AU - Norppa, Hannu

AU - Ceppi, Marcello

AU - Strömberg, Ulf

AU - Vermeulen, Roel

AU - Znaor, Ariana

AU - Cebulska-Wasilewska, Antonina

AU - Fabianova, Eleonora

AU - Fucic, Alexandra

AU - Gundy, Sarolta

AU - Hansteen, Inger-Lise

AU - Knudsen, Lisbeth E.

AU - Lazutka, Juozas

AU - Rossner, Pavel

AU - Sram, Radim J

AU - Boffetta, Paolo

PY - 2008/6

Y1 - 2008/6

N2 - Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07-1.60] and in the high (RR = 1.41; 95% CI = 1.16-1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34-3.68). The strongest association was found for stomach cancer [RR(medium) = 1.17 (95% CI = 0.37-3.70), RR(high) = 3.13 (95% CI = 1.17-8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.

AB - Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07-1.60] and in the high (RR = 1.41; 95% CI = 1.16-1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34-3.68). The strongest association was found for stomach cancer [RR(medium) = 1.17 (95% CI = 0.37-3.70), RR(high) = 3.13 (95% CI = 1.17-8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Chromosome Aberrations

KW - Cohort Studies

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Incidence

KW - Lymphocytes

KW - Male

KW - Middle Aged

KW - Neoplasms

KW - Risk Assessment

KW - Risk Factors

U2 - 10.1093/carcin/bgn075

DO - 10.1093/carcin/bgn075

M3 - Journal article

C2 - 18356148

SN - 0143-3334

VL - 29

SP - 1178

EP - 1183

JO - Carcinogenesis

JF - Carcinogenesis

IS - 6

ER -