Limits...
Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of non-small cell lung cancer in Andhra Pradesh region of South India.

Peddireddy V, Badabagni SP, Gundimeda SD, Mamidipudi V, Penagaluru PR, Mundluru HP - Eur. J. Med. Res. (2016)

Bottom Line: Assessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes.Results showed that CYP1A1 m1 'CC' genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 'AG' gene polymorphisms with 8.8-fold risk and GSTT1 (-/-) genotype demonstrated a twofold risk of disease susceptibility.A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500016, Telangana, India. vidyullatha.p@gmail.com.

ABSTRACT

Background: Lung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes. Reports on assessment of xenobiotic metabolizing genes like Cytochrome P 450 1A1 (CYP1A1), Glutathione -S -transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms from India are meagre, and reports from Andhra Pradesh are lacking.

Methods and results: Assessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes. Results showed that CYP1A1 m1 'CC' genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 'AG' gene polymorphisms with 8.8-fold risk and GSTT1 (-/-) genotype demonstrated a twofold risk of disease susceptibility.

Conclusions: A combined role of genetic polymorphisms and smoking status can be attributed for the cause of lung cancer. Further, the association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; CYP1A1 m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and GSTM1 with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2'-deoxyguanosine. A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.

No MeSH data available.


Related in: MedlinePlus

Amplifications of CYP1A1 m1 and the RFLP products of the polymorphic forms: a PCR for CYP1A1 m1 (340 bp) in multiple samples. bCYP1A1 m1 polymorphisms were detected by RFLP. The 340-bp PCR product was digested with Msp1 enzyme. Lanes4 and 9 represent homozygous major type (TT; 340 bp); Lanes3 and 12 represent homozygous minor (CC; 200 and 140 bp); Lanes1, 2, 5, 6, 7, 8, 10, 11, 13, 14 and 15 represent heterozygous type (TC; 340 bp, 200 and 140 bp)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4836067&req=5

Fig1: Amplifications of CYP1A1 m1 and the RFLP products of the polymorphic forms: a PCR for CYP1A1 m1 (340 bp) in multiple samples. bCYP1A1 m1 polymorphisms were detected by RFLP. The 340-bp PCR product was digested with Msp1 enzyme. Lanes4 and 9 represent homozygous major type (TT; 340 bp); Lanes3 and 12 represent homozygous minor (CC; 200 and 140 bp); Lanes1, 2, 5, 6, 7, 8, 10, 11, 13, 14 and 15 represent heterozygous type (TC; 340 bp, 200 and 140 bp)

Mentions: CYP1A1m1 and m2 polymorphisms were detected by RFLP. PCR amplification for CYP1A1 m1 produces 340-bp amplicons. A gain of Msp1 restriction site in the polymorphic allele resulted in 340-bp products for homozygous major type (TT), 200 and 140 bp for homozygous minor (CC), respectively (Fig. 1). BsrD1 restriction enzyme-based digestion was used to detect the CYP1A1m2 polymorphisms. In the case of ‘GG’ (homozygous minor), due to loss of the restriction sites, a single amplicon of 204 bp was obtained, whereas in the ‘AA’ (homozygous major) allele will generate two amplicons of sizes, 149 and 55 bp (Fig. 2). Multiplex PCR-based approach was employed to determine the genetic polymorphisms of GSTM1 and GSTT1 genes. Amplicons of 215 bp and 480 bp indicated the presence of GSTM1 and GSTT1 genes (Fig. 3).Fig. 1


Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of non-small cell lung cancer in Andhra Pradesh region of South India.

Peddireddy V, Badabagni SP, Gundimeda SD, Mamidipudi V, Penagaluru PR, Mundluru HP - Eur. J. Med. Res. (2016)

Amplifications of CYP1A1 m1 and the RFLP products of the polymorphic forms: a PCR for CYP1A1 m1 (340 bp) in multiple samples. bCYP1A1 m1 polymorphisms were detected by RFLP. The 340-bp PCR product was digested with Msp1 enzyme. Lanes4 and 9 represent homozygous major type (TT; 340 bp); Lanes3 and 12 represent homozygous minor (CC; 200 and 140 bp); Lanes1, 2, 5, 6, 7, 8, 10, 11, 13, 14 and 15 represent heterozygous type (TC; 340 bp, 200 and 140 bp)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836067&req=5

Fig1: Amplifications of CYP1A1 m1 and the RFLP products of the polymorphic forms: a PCR for CYP1A1 m1 (340 bp) in multiple samples. bCYP1A1 m1 polymorphisms were detected by RFLP. The 340-bp PCR product was digested with Msp1 enzyme. Lanes4 and 9 represent homozygous major type (TT; 340 bp); Lanes3 and 12 represent homozygous minor (CC; 200 and 140 bp); Lanes1, 2, 5, 6, 7, 8, 10, 11, 13, 14 and 15 represent heterozygous type (TC; 340 bp, 200 and 140 bp)
Mentions: CYP1A1m1 and m2 polymorphisms were detected by RFLP. PCR amplification for CYP1A1 m1 produces 340-bp amplicons. A gain of Msp1 restriction site in the polymorphic allele resulted in 340-bp products for homozygous major type (TT), 200 and 140 bp for homozygous minor (CC), respectively (Fig. 1). BsrD1 restriction enzyme-based digestion was used to detect the CYP1A1m2 polymorphisms. In the case of ‘GG’ (homozygous minor), due to loss of the restriction sites, a single amplicon of 204 bp was obtained, whereas in the ‘AA’ (homozygous major) allele will generate two amplicons of sizes, 149 and 55 bp (Fig. 2). Multiplex PCR-based approach was employed to determine the genetic polymorphisms of GSTM1 and GSTT1 genes. Amplicons of 215 bp and 480 bp indicated the presence of GSTM1 and GSTT1 genes (Fig. 3).Fig. 1

Bottom Line: Assessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes.Results showed that CYP1A1 m1 'CC' genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 'AG' gene polymorphisms with 8.8-fold risk and GSTT1 (-/-) genotype demonstrated a twofold risk of disease susceptibility.A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500016, Telangana, India. vidyullatha.p@gmail.com.

ABSTRACT

Background: Lung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes. Reports on assessment of xenobiotic metabolizing genes like Cytochrome P 450 1A1 (CYP1A1), Glutathione -S -transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms from India are meagre, and reports from Andhra Pradesh are lacking.

Methods and results: Assessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes. Results showed that CYP1A1 m1 'CC' genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 'AG' gene polymorphisms with 8.8-fold risk and GSTT1 (-/-) genotype demonstrated a twofold risk of disease susceptibility.

Conclusions: A combined role of genetic polymorphisms and smoking status can be attributed for the cause of lung cancer. Further, the association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; CYP1A1 m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and GSTM1 with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2'-deoxyguanosine. A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.

No MeSH data available.


Related in: MedlinePlus