Do GST polymorphisms modulate the frequency of chromosomal aberrations in healthy subjects?
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 [+ or -] 1.73 (mean [+ or -] 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 [+ or -] SD) for chromatid-type abberations (CTA) and chromosome-type aberrations (CSA) were 1.22 [+ or -] 1.21 and 1.15 [+ or -] 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 Vall05Val 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 Genotype No. Mean [+ or -] SD [[chi].sup.2] p-Value GSTT1 deletion Plus 356 2.26 [+ or -] 1.71 1.59 0.21 Null 74 2.59 [+ or -] 1.84 GSTM1 deletion Plus 223 2.28 [+ or -] 1.77 0.43 0.51 Null 208 2.36 [+ or -] 1.70 GS7P1 lle 105Val lle/lle 176 2.42 [+ or -] 1.91 2.25 0.33 lle/Val 219 2.19 [+ or -] 1.60 Val/Val 36 2.58 [+ or -] 1.61 CTA Genotype No. Mean [+ or -] SD [[chi].sup.2] p-Value GSTT1 deletion Plus 356 1.20 [+ or -] 1.21 0.88 0.35 Null 74 1.34 [+ or -] 1.29 GSTM1 deletion Plus 223 1.25 [+ or -] 1.28 0.01 0.90 Null 208 1.20 [+ or -] 1.17 GS7P1 lle 105Val lle/lle 176 1.31 [+ or -] 1.38 0.36 0.84 lle/Val 219 1.14 [+ or -] 1.08 Val/Val 36 1.31 [+ or -] 1.31 CSA Genotype No. Mean [+ or -] SD [[chi].sup.2] p-Value GSTT1 deletion Plus 356 1.11 [+ or -] 1.28 1.01 0.31 Null 74 1.29 [+ or -] 1.47 GSTM1 deletion Plus 223 1.04 [+ or -] 1.32 1.11 0.29 Null 208 1.18 [+ or -] 1.38 GS7P1 lle 105Val lle/lle 176 1.12 [+ or -] 1.34 1.27 0.53 lle/Val 219 1.07 [+ or -] 1.36 Val/Val 36 1.28 [+ or -] 1.37 Data, 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 colorectal 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 interscorer 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.
The authors declare they have no competing financial interests.
Institute of Experimental Medicine
Academy of Sciences of the Czech Republic
Prague, Czech Republic
Slovak Medical University
Bratislava, Slovak Republic
Jessenius Faculty of Medicine
Martin, Slovak Republic
National Institute of Public Health
Prague, Czech Republic
German Cancer Research Center
Boffetta P, van der Hel O, Norppa H, Fabianova E, Fucic A, Gundy S, et al. 2007. Chromosomal aberrations and cancer risk: results of a cohort study from Central Europe, Am J Epidemiol 165:36-43.
Hagmar L, Stromberg U, Bonassi S, Hansteen IL, Knudsen LE, Lindholm C, et al. 2004. Impact of types of lymphocyte chromosomal aberrations on human cancer risk: results from Nordic and Italian cohorts. Cancer Res 64:2258-2263.
Halasova E, Matakova T, Musak L, Valachova J, Vodickova L, Buchancova J, et al. 2007. Chromosomal aberrations and chromium blood levels in relation to polymorphisms of GSTM1, GSTTl and GSTP1 genes in welders. Chemicke Listy 101:97-99.
Musak L, Soucek P, Vodickova L, Naccarati A, Halasova E, Polakova V, et al. 2008. Chromosomal aberrations and polymorphisms in biotransformation and DNA repair genes among tire plant workers and controls. Mutat Res 641:36-42.
Naccarati A, Soucek P, Stetina R, Haufroid V, Kumar R, Vodickova L, et al. 2006. Genetic polymorphisms and possible gene-gene interactions in metabolic and DNA repair genes: effects on DNA damage. Mutat Res 593:22-31.
Norppa H, Bonassi S, Hansteen IL, Hagmar L, Stromberg U, Rossner P, et al. 2006. Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res 600:37-45.
Rossi AM, Hansteen IL, Skjelbred CF, Ballardin M, Maggini V, Murgia E, et al. 2009. Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1. Environ Health Perspect 117:203-208.
Slyskova J, Dusinska M, Kuricova M, Soucek P, Vodickova L, Susova S, et al. 2007. Relationship between the capacity to repair 8-oxoguanine, biomarkers of genotoxicity and individual susceptibility in styrene-exposed workers. Mutat Res 634:101-111.
Vodicka P, Kumar R, Stetina R, Musak L, Soucek P, Haufroid V, et al. 2004a. Markers of individual susceptibility and DNA repair rate in workers exposed to xenobiotics in a tire plant. Environ Mol Mutagen 44:283-292.
Vodicka P, Kumar R, Stetina R, Sanyal S, Soucek P, Haufroid V, et al. 2004b. Genetic polymorphisms in DNA repair genes and possible links with DNA-repair rates, chromosomal aberrations and single-strand breaks. Carcinogenesis 25:757-763.
Vodicka P, Soucek P, Tates AD, Dusinska M, Sarmanova J, Zamecnikova M, et al. 2001. Association between genetic polymorphisms and biomarkers in styrene-exposed workers. Mutat Res 482:89-103.
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|Title Annotation:||Correspondence; glutathione S-transferase|
|Author:||Vodicka, Pavel; Naccarati, Alessio; Vodickova, Ludmila; Polakova, Veronika; Dusinska, Maria; Musak,|
|Publication:||Environmental Health Perspectives|
|Date:||Sep 1, 2009|
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|Next Article:||GST polymorphisms: Bonassi et al. Respond.|