Protection against laryngeal and pharyngeal carcinoma: Heterozygous vs. homozygous deletions of GSTM1 and GSTT1

Abstract

Deletions in GSTM1 and GSTT1 genes are considered to be a risk factor for cancer development but the exact location of these deletions in the genome was unknown. Three main objectives of the current study were to: (a) identify the boundaries of these deletions in the human genome, (b) screen homozygous (-/-) and heterozygous (+/-) deleted, as well as homozygous present (+/+) individuals using PCR assays, (c) detect associations of pharyngeal (PC) and laryngeal cancer (LC) with the respective genotypes. In total, 102 PC and 92 LC patients were screened and compared with 150 controls. PCR mapping and sequencing revealed a 6 kbp deletion for GSTM1 and a 9 kbp deletion for the GSTT1 gene. The mean age of PC cases was 48.1 (±16.7) years; for LC cases it was 48.5 (±17.4) years and for controls 46 (±17.7) years. The OR (odds ratio) for the GSTM1 null genotype in PC and LC cases was 10.2 and 1.0 (95% CI 5.04-20.7 and 1.1-1.7) respectively. Similarly, for GSTT1 the OR was 4.02 with a 95% CI of 2.3-7.1 in PC cases. For LC cases the OR was 0.8 with 95% CI of 0.4-1.7. A non-significant number of LC and PC patients had heterozygous deletions of GSTM1 compared to controls (OD 0.5, 95% CI 0.2- 1.6 and OR 0.5, 95% CI 0.2- 1.5 respectively). The GSTT1 gene also showed a non-significant association in PC (OD 0.9, 95% CI 0.4-1.9), as well as in LC patients (OD 0.7, 95% CI 0.3-1.7). The homozygous genotype was significantly associated with PC and LC, whereas the heterozygous was not so. The GSTM1 (-/-) and GSTT1 (-/-) genotypes are a risk factor for LC and PC, whereas the (+/-) genotypes are not.

Keywords: GSTM1; GSTT1 heterozygous; cancer; deletions; homozygous.

Figure 1

Bioedit graph representing GSTM1 and GSTT1 gene deletions of approximately 6 kbp (a) and 9 kbp (b). The upstream and downstream intronic portions were present, but the complete gene-containing sequence was lacking.

Figure 2

Agarose gel electrophoresis results showing exonic and deletion-specific bands corresponding to homozygous present (+/+), heterozygous (+/−) and homozygous deleted gene (−/−) samples.