Association between Frequency of Chromosomal Aberrations and Cancer Risk Is Not Influenced by Genetic Polymorphisms in GSTM1 and GSTT1

Abstract

BackgroundThe frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes.ObjectivesTo evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk.MethodsA case–control study was performed pooling data from cytogenetic studies carried out in 1974–1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency.ResultsThe association between CA frequency and cancer risk was confirmed [ORmedium (odds ratio)medium = 1.5, 95% credibility interval (CrI), 0.9–2.5; ORhigh = 2.8, 95% CrI, 1.6–4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (ORhigh= 9.4, 95% CrI, 2.6–28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (ORhigh= 6.2, 95% CrI, 1.5–20.0), the genitourinary tract (ORhigh = 4.0, 95% CrI, 1.4–10.0), and the digestive tract (ORhigh = 2.8, 95% CrI, 1.2–5.8).ConclusionsDespite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.

Genotoxic effect of exposure to metal(loid)s. A molecular epidemiology survey of populations living and working in Panasqueira mine area, Portugal

“…In the present study we found a significant influence of GSTM1 on the effect of exposure to genotoxic agents. This polymorphic gene has been extensively studied, as individuals presenting the null genotype have a decreased ability to detoxify carcinogens, thus having a higher sensitivity to genetic damage and an increased cancer risk (Rossi et al, 2009). Accordingly, our results showed among the control group a higher CA-chromosome MR in the GSTM1 null individuals.…”

“…lower CA-total and CA-chromosome MRs . Two of the major studies which evaluated the influence of GSTM1 deletion on CA frequencies were performed by Rossi et al (2009) andSkjelbred et al (2011). None of these studies, that investigated cancer cases vs. control individuals and a population of healthy individuals, respectively, found any significant effect of these modifications.…”

Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects

“…Human cancers are often associated with chromosomal instability (both numerical and structural CAs) in the cells (11)(12)(13); these aberrations are also considered as causative events in malignant transformation (14). Frequencies of CA in PBL are predictive for cancer risk in prospective epidemiological studies (15)(16)(17), and patients with many types of cancer show elevated CAs at the time of diagnosis (10,18,19).…”

Novel Approaches in Genetic Toxicology of Pesticides by Applying Fluorescent in Situ Hybridization Technique

“…Over the last decade, chromosomal aberration analysis, micronucleus, and comet assay have emerged as most reliable in evaluation of genotoxic effect of human exposure to pesticides. Among them, chromosomal aberrations and micronuclei as biomarkers of the effect were also proved to be good predictors in cancer risk assessment (Fenech, 2007;Rossi et al, 2009). …”