The Relation between Polymorphisms in Exon 5 and Exon 6 of GSTP1 Gene and the Risk of Lung Cancer in Iranian People

Document Type : Research Articles

Authors

1 Department of Biochemistry and Genetics, Lorestan University of Medical Sciences, Khorramabad, Iran.

2 Department of Pulmonary, Lorestan University of Medical Science, Khorramabad, Iran.

3 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

5 Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.

Abstract

Objective: The GSTP1 gene, which is located on chromosome 11q13, consists of 7 exons and 6 introns. There
are two polymorphisms in GSTP1 that have been exposed to a transposition for codon 105 (Ile/Val) and 114 (Ala/Val)
in exons 5 and 6, which have been studied previously in relation to lung cancer. Since the level of GSTP1 expression
in lung tissues and other human epithelial tissues is high, GSTP1Val-105 polymorphism is recognized as a sensitive
factor for tobacco-related cancers, especially lung cancer. Methods: One hundred and twenty tissue block samples
of patients with lung cancers and 120 peripheral blood samples of the control group were obtained from two referral
cancer centers in Tehran, Iran, from 2011 to 2016. Genomic DNA was extracted from tissue blocks and buffy coat of
study cases to detect SNP of GSTP1 gene using Tetra-primer ARMS-PCR. Results: There was a notable correlation
between the incidence of lung cancer and variant Val105 (P-value=0.001; OR=2/6; 95% CI=1.49-4.53) and Ile105
(P-value=0.003; OR=0.41; 95% CI=0.23-0.73). The odds ratio for lung cancer in the homozygous Ile105/Ile105
genotype was 3.56 times higher than that of individual with heterozygous Ile105/Val105 (P-value<0.001; OR=3/56;
95% CI=1.826-6.934) genotype, that was statistically significant. Furthermore, the results showed that there was no
significant correlation between Ala114/Val114 genotypes and lung cancer. The BC (P-value=0.007; OR=0.16; 95%
CI=0.04-0.61) and AA (P=0.001) genotypes were statistically significant (P-value <0.05); and for those who had AA
genotype, the odds ratio was almost six times higher than those with BC genotype. Conclusions: The study of GSTP1
polymorphisms indicated that unlike the polymorphism in exon 5, the GSTP1 exon 6 polymorphism correlated with
the lung cancer risk in the select group of Iranian people. Likewise, the potential use of this genetic polymorphism as
a lung cancer predictor is confirmed.

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