Glutathione S-transferase and cytochrome-P-450 polymorphism as risk factors for squamous cell carcinoma of the larynx

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Purpose

While cigarette smoking and alcohol consumption are recognized covariates for laryngeal carcinoma, the role of genetic factors in determining individual susceptibility is unknown. We describe the influence of polymorphism in carcinogen-metabolizing enzymes on susceptibility to squamous cell carcinoma of the larynx.

Material and methods

We investigated 269 patients with T1-T4 laryngeal carcinoma and 216 controls. Enzyme genotypes at the glutathione-Stransferase GSTM1 (A, B, A/B, null), GSTM3 (A, B), GSTT1 (null and expressors), and cytochrome P-450, CYP2D6 (intron 3/exon 4 boundary mutation and exon 5 deletion), CYP1A1 (3′-mutation and exon 7 mutation), and CYP2E1 (mutation at the 5′ flanking region) loci were determined using polymerase chain reaction and restriction-based approaches.

Results

While the frequencies of the heterozygote GSTM1 A/B and homocygote GSTM3 B/ B were statistically significantly lower in cases than controls, the frequency of the GSTT1 null genotype was higher in the cases than controls. Genotype frequencies of 123 patients suffering squamous cell carcinomas located at different sites within the upper aerodigestive tract showed no differences between cases and controls.

Conclusions

The data provide evidence that susceptibility to laryngeal carcinoma, but not pharyngeal carcinoma, is mediated by allelism at a number of loci encoding enzymes involved in the detoxification of electrophils derived from environmental pollution including cigarette smoke.

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    With the step of screening the title or abstract, 20 eligible studies were selected. Of the 20 articles selected, 6 studies were excluded because of the lack of data about GSTT1 status of laryngeal cancer (Boccia et al., 2008; Cabelguenne et al., 2001; Gronau et al., 2003; Li et al., 2009; Olshan et al., 2000; Peters et al., 2006), the study by Jahnke et al, (1996) was excluded because the subjects had been included by the study of Jahnke et al. (1997), the study by Hanna et al. (2001) was excluded because polymorphism was determined in fresh frozen tissue specimens. Finally, 12 studies (Acar et al., 2006; Chatzimichalis et al., 2010; Gajecka et al., 2005; Hong et al., 2000; Jahnke et al., 1995, 1997; Jourenkova et al., 1998; Matthias et al., 1998; Risch et al., 2003; Tian et al., 2011; To-Figueras et al., 2002; Unal et al., 2004) including 2124 laryngeal SCC cases and 2059 controls were included in this meta-analysis based on inclusion and exclusion criteria (Table 1).

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