The Association between Epidermal Growth Factor Receptor (EGFR) Gene Polymorphisms and Lung Cancer Risk

Bashir, Nabil; Ragab, Entesar S; Khabour, Omar F.; Khassawneh, Basheer; Alfaqih, Mahmoud A.; Momani, Jafar

doi:10.3390/biom8030053

Cited by 13 publications

(6 citation statements)

References 37 publications

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“…Autophosphorylation of EGFR tyrosine kinase domains leads to activation of downstream proteins that mediate cell proliferation and cell survival 6 and was reported to play an important role in tumorigenesis and progression of lung adenocarcinomas 7. The EGFR gene was reported to harbor mutations and/or polymorphisms that increase susceptibility to lung cancer 8. Most of these mutations/polymorphisms exist within the catalytic kinase domain, which increases EGFR activity.…”

Section: Introductionmentioning

confidence: 99%

Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients

Wu¹,

Chien²,

Chou³

et al. 2019

J. Cancer

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High-mobility group protein box 1 (HMGB1) is overexpressed and reported to be a prognostic factor in patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutants play an important role in NSCLC progression. The aim of this study was to explore potential associations between genetic polymorphisms of HMGB1 and EGFR mutations in a cohort that included 280 patients with NSCLC, some of whom were smokers and others who never smoked. Four tagged single-nucleotide polymorphisms (SNPs) of HMGB1 were detected by a TaqMan-based real-time polymerase chain reaction (PCR) in patients. We found that after adjusting for other covariates, NSCLC patients who smoked and who respectively had CG, CT, and TC heterozygotes of HMGB1 rs2249825, rs1045411, and rs1360485, were at lower risk of developing mutant EGFR , compared to those patients with wild-type homozygotes. Moreover, significant inverse associations between the CG and CG + GG genotypes of HMGB1 rs2249825 and the EGFR hotspot mutation, an exon 19 in-frame deletion, were also observed among NSCLC patients. Within patients harboring mutant EGFR , HMGB1 rs1360485 C (TC + CC) allele carriers were at higher risk of developing poorly differentiated cancer types (odds ratio=5.493, 95% confidence interval: 1.130~26.696, p =0.019), compared to patients with TT homozygotes. Furthermore, we found that HMGB1 rs1360485 polymorphisms seemed to be related to susceptibility to developing poorly differentiated cancer linked to tobacco consumption in EGFR mutant patients. In conclusion, our results suggested that HMGB1 variants are significantly inversely associated with EGFR mutations among NSCLC patients who smoked. HMGB1 variants and tobacco consumption might contribute to the pathological development of NSCLC.

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Section: Introductionmentioning

confidence: 99%

Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients

Wu¹,

Chien²,

Chou³

et al. 2019

J. Cancer

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“…Likewise, certain EGFR genetic variations have also been shown to change EGFR protein levels in the body, including lungs (Nie et al, 2015), and subsequently modulate cancer susceptibility. In accordance with this, the variations in EGFR gene have been shown to modulate risk of several types of cancers, including gastric (Torres-Jasso et al, 2015), bladder (Chu et al, 2013), breast (Sobti et al, 2012) and lung cancer (Bashir et al, 2018;Feng et al, 2014;X. Liu et al, 2017).…”

Section: Discussionmentioning

confidence: 57%

“…In Jordan, lung cancer is the third most common cancer, following breast and colorectal cancers (Ismail et al, 2013). A recent study has shown an association between EGFR rs712829 and rs2072454 SNPs with the risk of lung cancer among Jordanians (Bashir et al, 2018). In the current investigation, the relationship between two other SNPs in EGFR (rs2233947 and rs884225) and lung cancer risk was studied.…”

Section: Introductionmentioning

confidence: 89%

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The EGFR rs2233947 polymorphism is associated with lung cancer risk: a study from Jordan

et al. 2019

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The epidermal growth factor receptor (EGFR) is a tyrosine kinase cell surface protein that plays a role in the process of carcinogenesis. In this study, we investigated the association between EGFR rs2233947 and rs884225 SNPs and the risk of lung cancer. A total of 258 participants (129 lung cancer patients and 129 healthy controls) took part in the study. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique was used to genotype EGFR SNPs. A strong association was detected between rs2233947 and lung cancer (P<0.01). Compared with the rs2293347 GG genotype, the AA/AG genotypes were associated with a significantly decreased risk of lung cancer (adjusted OR = 0.28, 95% confidence interval [CI]=0.13–0.61, P<0.01). EGFR rs2233947 correlated with lung cancer in males, smokers, and in the squamous cell carcinoma lung cancer subtype (P<0.01). Haplotype analysis of rs2233947 and rs884225 showed that the AA haplotype was associated with a significantly decreased risk of lung cancer (P<0.01). The data presented in the current study support a protective role for the rs2233947 A allele against the development of lung cancer. This result, however, requires further validation in a larger population.

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“…EGFR activation by metals has been supposed to be involved in some neurodegenerative diseases [29,30]. To date, genetic studies have demonstrated that EGFR polymorphisms may modify the risk for head and neck squamous cell carcinoma (HNSCC), lung cancer, renal cancer, and so on [31][32][33]. Nevertheless, there were no studies about the relationship between metals, kidney function, and EGFR polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

The Association of Renal Function and Plasma Metals Modified by EGFR and TNF-α Gene Polymorphisms in Metal Industrial Workers and General Population

Chen

Huang

Lee

et al. 2021

IJERPH

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Exposure to metals may be associated with renal function impairment, but the effect modified by genetic polymorphisms was not considered in most studies. Epidermal growth factor receptor (EGFR) and tumor necrotic factor-α (TNF-α) play important roles in renal hemodynamics, and they have been reported to be associated with some renal diseases. The aim of our research is to explore whether genetic variations in EGFR and TNF-α have influence on renal function under exposure to various metals. This cross-sectional study consisted of 376 metal industrial workers, 396 participants of Taiwan Biobank, and 231 volunteers of health examinations. We identified 23 single nucleotide polymorphisms (SNPs) on the EGFR gene and 6 SNPs on the TNF-α gene, and we also measured their plasma concentration of cobalt, copper, zinc, selenium, arsenic, and lead. Multiple regression analysis was applied to investigate the association between various SNPs, metals, and renal function. Our results revealed some protective and susceptible genotypes under occupational or environmental exposure to metals. The individuals carrying EGFR rs2280653 GG might have declined renal function under excessive exposure to selenium, and those with EGFR rs3823585 CC, rs12671550 CC, and rs4947986 GG genotypes might be susceptible to lead nephrotoxicity. We suggest the high-risk population to prevent renal diseases.

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The Association between Epidermal Growth Factor Receptor (EGFR) Gene Polymorphisms and Lung Cancer Risk

Cited by 13 publications

References 37 publications

Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients

Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients

The EGFR rs2233947 polymorphism is associated with lung cancer risk: a study from Jordan

The Association of Renal Function and Plasma Metals Modified by EGFR and TNF-α Gene Polymorphisms in Metal Industrial Workers and General Population

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