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Do GST Polymorphisms Modulate the Frequency of Chromosomal Aberrations in Healthy Subjects?

2009; National Institute of Environmental Health Sciences; Volume: 117; Issue: 9 Linguagem: Inglês

10.1289/ehp.0900838

1552-9924

Pavel Vodička, Alessio Naccarati, Ľudmila Vodičková, Veronika Poláková, Mária Dušinská, Ľudovít Mušák, Erika Halašová, Simona Šůsová, Pavel Souček, Kari Hemminki,

DNA Repair Mechanisms

Vol. 117, No. 9 PerspecitivesOpen AccessDo GST Polymorphisms Modulate the Frequency of Chromosomal Aberrations in Healthy Subjects? Pavel Vodicka, Alessio Naccarati, Ludmila Vodickova, and Veronika Polakova Maria Dusinska Ludovit Musak and Erika Halasova Simona Susova and Pavel Soucek Kari Hemminki Pavel Vodicka , Alessio Naccarati , Ludmila Vodickova , Veronika Polakova , Maria Dusinska , Ludovit Musak , Erika Halasova , Simona Susova , Pavel Soucek , and Kari Hemminki Published:1 September 2009https://doi.org/10.1289/ehp.0900838Cited by:7AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Rossi et al. (2009) described an association between chromosomal aberration (CA) frequency and cancer risk in a case–control study on 107 cancer cases and 291 controls, whereby they observed no modifying effect of polymorphisms in glutathione S-transferase M1 (GSTM1) and GSTT1.In our studies of 488 healthy individuals who shared the same environmental exposure in Slovakia and the Czech Republic, we observed a CA frequency of 2.35 ± 1.73 (mean ± SD) (Halasova et al. 2007; Musak et al. 2008; Naccarati et al. 2006; Slyskova et al. 2007; Vodicka et al. 2001, 2004a, 2004b). The frequencies (mean ± SD) for chromatid-type abberations (CTA) and chromosome-type aberrations (CSA) were 1.22 ± 1.21 and 1.15 ± 1.35, respectively. By analyzing modulating effects of genetic polymorphisms in GSTT1, GSTM1, and GSTP1 on CAs, CTAs, and CSAs (Table 1), we found no significant association between chromosomal damage and any of the studied polymorphisms. The results were further confirmed by logistic regression: for the GSTT1 null genotype, odds ratio (OR) = 1.35 [95% confidence interval (CI), 0.79–2.32; p = 0.27]; for the GSTM1 genotype, OR = 1.09 [95% CI, 0.74–1.62; p = 0.65]; and for a variant GSTP1 Val105Val genotype, OR = 0.83 [95% CI, 0.55–1.24; p = 0.36]. These data on a larger healthy population [previously published separately by Halasova et al. (2007), Musak et al. (2008), Naccarati et al. (2006), Slyskova et al. (2007), and Vodicka et al. (2001, 2004a, 2004b)] confirm the findings of Rossi et al. (2009) regarding GSTM1 and GSTT1 polymorphisms. Additionally, in our reanalysis, we did not observe any modulating effect of GSTP1 polymorphism on CA frequency. However, the modulating role of GST polymorphisms may not be excluded, particularly in interaction with heavy occupational exposure. In our study exploring chromosomal damage in tire-plant workers (Musak et al. 2008), CAs were significantly higher in subjects with GSTT1-null than in those with GSTT1-plus genotypes, particularly in association with smoking.Table 1 Distribution of analyzed genotypes and CA frequencies.CA CTA CSA GenotypeNo.Mean ± SDχ2p-ValueMean ± SDχ2p-ValueMean ± SDχ2p-ValueGSTT1 deletion Plus3562.26 ± 1.711.590.211.20 ± 1.210.880.351.11 ± 1.281.010.31Null742.59 ± 1.841.34 ± 1.291.29 ± 1.47GSTM1 deletion Plus2232.28 ± 1.770.430.511.25 ± 1.280.010.901.04 ± 1.321.110.29Null2082.36 ± 1.701.20 ± 1.171.18 ± 1.38GSTP1 Ile105Val Ile/Ile1762.42 ± 1.912.250.331.31 ± 1.380.360.841.12 ± 1.341.270.53Ile/Val2192.19 ± 1.601.14 ± 1.081.07 ± 1.36Val/Val362.58 ± 1.611.31 ± 1.311.28 ± 1.37Data, pooled and recalculated from previously published data (Halasova et al. 2007; Musak et al. 2008; Naccarati et al. 2006; Slyskova et al. 2007; Vodicka et al. 2001, 2004a, 2004b), were analyzed by the Kruskal-Wallis test.In the past decade, CAs have been accepted as a predictive marker of cancer (Hagmar et al. 2004), particularly for colo-rectal and lung cancers (Boffetta et al. 2007; Norppa et al. 2006). Nevertheless, these studies, as well as the study of Rossi et al. (2009) may have limitations: For example, cohorts were recruited in various regions with different lifestyle and environmental backgrounds, and different laboratories were involved in processing and scoring the samples over many years. In earlier studies, virtually no data on individual susceptibility were available because of the lack of DNA for molecular analysis.The data on CAs presented here were obtained on healthy subjects from a homogeneous region with fairly similar socioeconomic background. The analysis of CAs reported in these studies (Halasova et al. 2007; Musak et al. 2008; Naccarati et al. 2006; Slyskova et al. 2007; Vodicka et al. 2001, 2004a, 2004b) were performed in two laboratories, using the same protocol and the same scoring criteria with regular slide exchanges to minimize interlaboratory and inter scorer differences. Also, native DNA from whole-blood samples for molecular genetic studies was collected simultaneously with the samples for cytogenetic investigations.Future prospective studies regarding CAs and cancer should be designed by taking into account the lifestyle and occupational/environmental exposures, along with factors of individual susceptibility. Some GST polymorphisms may modulate CA frequency through interaction with environmental factors. The next logical step for a confirmation of predictive values of CA frequencies in relation to cancer will be their determination in lymphocytes of cancer patients in association with clinical– pathological characteristics.ReferencesBoffetta P, van der Hel O, Norppa H, Fabianova E, Fucic A, Gundy Set al.. 2007. Chromosomal aberrations and cancer risk: results of a cohort study from Central Europe. Am J Epidemiol 165:36-4317071846. Crossref, Medline, Google ScholarHagmar L, Strömberg U, Bonassi S, Hansteen IL, Knudsen LE, Lindholm Cet al.. 2004. 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Vol. 117, No. 9 September 2009Metrics About Article Metrics Publication History Originally published1 September 2009Published in print1 September 2009 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.