Background:
Glutathione S-transferases play an important role in detoxification of a wide range of human carcinogens. Functional polymorphisms have been identified in the GSTM1, GSTT1, GSTP1 genes, which may alter the risk of lung cancer among individuals exposed to coal, wood, and biomass smoke, and cooking oil fumes.
Methods:
We have evaluated the association between the GSTM1, GSTT1, GSTP1 Ile105Val and GSTP1 Ala114Val polymorphisms and lung cancer risk. All genotypes were detected by reverse hibridization method. Demographics datas, genotypes and allele frequencies are evaluated.
Results:
Prospectively 351 lung cancer and 103 control cases included to the study from 7 centers in Turkey. Mean age was 60 years and 76.4% of them were male. Subgroups of the cases are shown in table 1. All genotypes of four polymorphisms are found similar between the cancer and control group (table 2). Although we found no statisticaly significant correlation between the polymorphisms and occupational risk, smoke cessation, living area, biomass exposure and familial cancer history (p>0,05). GSTP1 *105 and *114 compaund heterozygote genotypes increase the lung cancer risk approximately 2,5 folds (OR=2,463;p=0,051). Moreover GST *105 and *114 compaund heterozygote genotypes increase squamous cell cancer risk 3 folds (OR=2,992;p=0,028) and undiferantial carcinoma risk 4 folds (OR=4.015;p=0.016). Table 1.Lung cancer subgroups
| n | % |
Squamous cell carcinoma | 133 | 37,9 |
Adenocarsinoma | 98 | 27,9 |
Undifferentiated carcinoma | 55 | 15,7 |
Small cell carcinoma | 47 | 13,4 |
Large cell carcinoma | 10 | 2,8 |
Adenosquamous carcinoma | 8 | 2,3 |
Table 2.GSTM1/T1/*105/*114 Genotype Distributions in Lung Cancer and Control Cases Genotypes | | Lung cancer | Lung cancer | Control | Control | p |
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| | n | % | n | % | |
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Ile105Val | AA | 169 | 48,1 | 56 | 54,4 | |
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Ile105Val | AG | 158 | 45,0 | 39 | 37,9 | 0,437 |
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Ile105Val | GG | 24 | 6,8 | 8 | 7,7 | |
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Ala114Val | CC | 289 | 82,3 | 88 | 85,4 | |
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Ala114Val | CT | 60 | 17,1 | 15 | 14,6 | 0,610 |
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Ala114Val | TT | 2 | 0,6 | 0 | 0,0 | |
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GSTM1 | (+) | 187 | 53,3 | 52 | 50,5 | 0,654 |
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| (-) | 164 | 46,7 | 51 | 49,5 | |
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GSTT1 | (+) | 253 | 72,1 | 75 | 72,8 | 1,00 |
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| (-) | 98 | 27,9 | 28 | 27,2 | |
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| | | | | | |
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Total | | 351 | 100,0 | 103 | 100,0 |
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Conclusion: In order to the most frequent lung cancer type is adenocarcinoma in world wide, our study indicate that epidermoid carcinoma was the most frequent type in our country. Recent studies showed that GST genes are expressed at human epitelial tissues including lungs. GST gene expressions are overexpressed expecially tumor tissues. Our results indicate that GST polymorphisims may play an important role at tumor pathogenesis. Therefore GSTP1 Ile105Val and Ala114Val functional polymorphisims’ mutant genotypes are more relevant for Squamous cell and Undifferentiated carcinoma pathogenesis.