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Genetic polymorphism of lysyl oxidase, glutathione S-transferase M1, glutathione-S-transferase T1, and glutathione S-transferase P1 genes as risk factors for lung cancer in Egyptian patients

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Abstract

Lung cancer is a lethal malignancy and is affected by genetic polymorphisms that contribute to an individual’s susceptibility to developing the disease. Several studies on lung cancer showed conflicting results. The aim of this study is to investigate whether individual or combined modifying effects of LOX G/A, GSTM1 active/null, GSTT1 active/null and GSTP1 Ile/Val polymorphisms are related to the risk of lung cancer in relation to smoking in the Egyptian population. This study is a hospital-based case control study that included 200 patients and 200 control subjects. Genotyping of the 4 studied genes was determined by Multiplex PCR for GSTM1 and GSTT1 and Taq man SNP assay for GSTP1 and LOX genes. The LOX G/A and GSTP1 Ile/Val in both homozygous and heterozygous variants, and the GSTM1 and GSTT1 null genotype showed significant association with lung cancer. Combination between gene polymorphism and smoking increased the risk of developing cancer by 2.7 fold in the LOX GA+AA variant, 1.9 fold in the GSTM1 null variant, 4.8 fold in the GSTT1 null variant and 4.3 fold in the GSTP1 Ile/Val+Val/Val variant. The genetic combination (LOX GA+AA/GSTT1 active, LOX GG/GSTT1 null, LOX GA+AA/GSTT1 null, LOX GA+AA/GSTP1 Ile/Ile, LOX GG/GSTP1 Ile/Val+Val/Val and LOX GA+AA/GSTP1 Ile/Val+Val/Val) led to a higher lung cancer risk, compared to the reference group. The LOX GA/AA, GSTM1 null, GSTT1 null and GSTP1 Ile/Val, Val/Val genotypes contributed to increased lung cancer susceptibility. To the best of our knowledge, this is the first study of LOX genotyping in the Egyptian population. The combination of genotypes increased the risk of cancer, indicating the importance of gene–gene interaction and giving a targeted preventive approach.

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Abbreviations

LOX :

Lysyl oxidase

LOX1-4:

Four LOX-like proteins

GSTs:

Glutathione S-transferases

GSTM1 :

Glutathione-S-transferase M1

GSTT1 :

Glutathione-S-transferase T1

GSTP1 :

Glutathione-S-transferase P1

NS:

Non-smoker

S:

Smoker

LC:

Lung cancer

SCC:

Squamous cell carcinoma

AC:

Adenocarcinoma

Small CC:

Small cell carcinoma

Large CC:

Large cell carcinoma

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Funding

Science and Technology Development Fund (STDF), Ministry of State for Scientific Research, Egypt. Project ID: 5424.

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Authors and Affiliations

  1. Medical Biochemistry Department, Faculty of Medicine, Assiut University, Assiut, Egypt

    Sahar E. M. El-Deek, Soad M. Abdel-Ghany, Randa S. Hana, Naglaa T. El-Melegy & Ayat A. Sayed

  2. Chest Department, Faculty of Medicine, Assiut University, Assiut, Egypt

    Aliaa A. R. Mohamed

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  1. Sahar E. M. El-Deek
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  2. Soad M. Abdel-Ghany
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  3. Randa S. Hana
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  4. Aliaa A. R. Mohamed
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Contributions

SEMED, SMAG and AAS researched literature and conceived the study, collection of data and related papers, obtaining ethical approval, performing and monitoring clinical lab work, data entry and analysis, wrote the manuscript. RSH, and AARM collected the samples. NTEM revised the paper. All authors reviewed and approved the final version of manuscript.

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Correspondence to Sahar E. M. El-Deek.

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El-Deek, S.E.M., Abdel-Ghany, S.M., Hana, R.S. et al. Genetic polymorphism of lysyl oxidase, glutathione S-transferase M1, glutathione-S-transferase T1, and glutathione S-transferase P1 genes as risk factors for lung cancer in Egyptian patients. Mol Biol Rep 48, 4221–4232 (2021). https://doi.org/10.1007/s11033-021-06436-4

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