Abstract
Background
Lung carcinoma is a foremost cause of cancer-related mortality worldwide. Variable genetic factors are associated with the development of lung cancer. This study was performed to evaluate the possible association of epidermal growth factor receptor (EGFR) gene polymorphisms with non small cell lung carcinoma (NSCLC) in Iraqi population.
Methods
DNA samples were extracted from 100 patients and 100 controls. Four PCR fragments were designed to amplify four high-frequency variants within EGFR, namely rs1050171, rs2072454, rs2227984, and rs2227983. The PCR fragments were genotyped by single-strand conformation polymorphism (SSCP) method, and each genotype was subjected to direct sequencing.
Results
Genotyping experiments confirmed the variability of three targeted variants, and logistic regression analysis showed that two of these variants (rs1050171 and rs2227983) tend to exhibit a significant association with NSCLC. Individuals with rs1050171:GA genotype showed a possible association with the increased risk of NSCLC (P = 0.0110; OD 5.2636; Cl95% 1.4630 to 18.9371). Individuals with rs2227983:GG genotype exhibited a potential association with NSCLC (P = 0.0037; OD 5.2683; Cl95% 1.7141 to 16.1919). Linkage disequilibrium analysis showed that the effects of the investigated variants seem to take independent actions, and no haplotype was found to be associated with the high prevalence of NSCLC.
Conclusions
Our collective data indicated that EGFR-rs1050171G/A and EGFR-rs2227983G/G SNPs tend to exert significant and separate associations with the increased risk of NSCLC. However, this study recommends using a broader spectrum of the investigated samples to get further details of both SNPs in terms of their association with the susceptibility to NSCLC.
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Data availability
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available privacy and ethical restrictions, as stipulated by the University of Kufa Institutional Review Board.
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Acknowledgements
The authors would like to acknowledge the Middle-Euphrates Cancer Center (MECC), Najaf province, and Merjan Cancer Center (MCC), Babil province for granting the samples and providing informative scientific help to accompany the preliminary data preparations.
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ZKL developed the work, and conducted genotyping experiments. MBSA contributed to the supervision of the work, analyzed the data, and wrote the manuscript. TMA supervised the research. AHA participated in the genotyping experiments. All authors approved the final version of the work.
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The experiments performed in the study were conducted following the Helsinki Declaration for experiments involving people and the biochemical research involving human subjects was approved by the Institutional Review Board (IRB) in the University of Kufa (IECIH/UOK 088/2020; CAAE 08802212). Signed written informed consents were obtained from all participants before being involved in the study.
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Lawi, Z.K., Al-Shuhaib, M.B.S., Amara, I.B. et al. Two missense variants of the epidermal growth factor receptor gene are associated with non small cell lung carcinoma in the subjects from Iraq. Mol Biol Rep 49, 11653–11661 (2022). https://doi.org/10.1007/s11033-022-07933-w
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DOI: https://doi.org/10.1007/s11033-022-07933-w