Dataset Information

Detection of EGFR gene polymorphisms in non-small cell lung cancer Egyptian patients: a case-control study.

ABSTRACT:

Background

Non-Small Cell Lung Cancer displays several genetic mutations including epidermal growth factor receptor. This study's objective was to determine if the EGFR exon19 rs121913438 and exon21 rs121434568 variations play a role in NSCLC susceptibility.

Methods

Case-control research was done at the Mansoura university oncology center including 124 NSCLC patients, and 124 healthy volunteers. blood was used to obtain genomic DNA. ARMS-PCR was used to genotype single-nucleotide polymorphisms.

Results

Molecular study for EGFR exon 19 del. showed NSCLC cases were significantly associated with a higher proportion of heterozygous WD, WD + DD dominant genotypes, and mutant D allele, (p < 0.05 for each), with a risk to develop NSCLC. also, NSCLC cases were significantly associated with a higher proportion of heterozygous TG, TG + GG dominant genotype, G mutant allele, (p < 0.05 for each), with a risk to develop LC (OR > 1 for each). regarding the two EGFR mutations, TTF1 staining was significantly associated with WD + DD genotypes for EGFR exon 19 del But not EGFR exon 21. No substantial differences were found among all studied cases with CK7 or napsin A Tumor cytochemistry.

Conclusions

The WD heterozygous genotype and D allele in exon 19 del. mutation as well as the TG heterozygous and G allele in exon 21 substitution mutation in EGFR gene are strongly associated with the development of advanced-NSCLC in the Egyptians.

SUBMITTER: El-Khawaga OY

PROVIDER: S-EPMC10680232 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Detection of EGFR gene polymorphisms in non-small cell lung cancer Egyptian patients: a case-control study.

El-Khawaga Omali Y OY Al-Azzawy Mohammed F MF ElSaid Afaf M AM Refaat Sherif S El-Dawa Aliaa N AN

Genes and environment : the official journal of the Japanese Environmental Mutagen Society 20231127 1

<h4>Background</h4>Non-Small Cell Lung Cancer displays several genetic mutations including epidermal growth factor receptor. This study's objective was to determine if the EGFR exon19 rs121913438 and exon21 rs121434568 variations play a role in NSCLC susceptibility.<h4>Methods</h4>Case-control research was done at the Mansoura university oncology center including 124 NSCLC patients, and 124 healthy volunteers. blood was used to obtain genomic DNA. ARMS-PCR was used to genotype single-nucleotide ...[more]

PMID: 38008767

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Project description:BackgroundThe epidermal growth factor receptor (EGFR) gene is the prototype member of the type I receptor tyrosine kinase (TK) family and plays a pivotal role in cell proliferation and differentiation. There are three well described polymorphisms that are associated with increased protein production in experimental systems: a polymorphic dinucleotide repeat (CA simple sequence repeat 1 [CA-SSR1]) in intron one (lower number of repeats) and two single nucleotide polymorphisms (SNPs) in the promoter region, -216 (G/T or T/T) and -191 (C/A or A/A). The objective of this study was to examine distributions of these three polymorphisms and their relationships to each other and to EGFR gene mutations and allelic imbalance (AI) in non-small cell lung cancers.Methods and findingsWe examined the frequencies of the three polymorphisms of EGFR in 556 resected lung cancers and corresponding non-malignant lung tissues from 336 East Asians, 213 individuals of Northern European descent, and seven of other ethnicities. We also studied the EGFR gene in 93 corresponding non-malignant lung tissue samples from European-descent patients from Italy and in peripheral blood mononuclear cells from 250 normal healthy US individuals enrolled in epidemiological studies including individuals of European descent, African-Americans, and Mexican-Americans. We sequenced the four exons (18-21) of the TK domain known to harbor activating mutations in tumors and examined the status of the CA-SSR1 alleles (presence of heterozygosity, repeat number of the alleles, and relative amplification of one allele) and allele-specific amplification of mutant tumors as determined by a standardized semiautomated method of microsatellite analysis. Variant forms of SNP -216 (G/T or T/T) and SNP -191 (C/A or A/A) (associated with higher protein production in experimental systems) were less frequent in East Asians than in individuals of other ethnicities (p < 0.001). Both alleles of CA-SSR1 were significantly longer in East Asians than in individuals of other ethnicities (p < 0.001). Expression studies using bronchial epithelial cultures demonstrated a trend towards increased mRNA expression in cultures having the variant SNP -216 G/T or T/T genotypes. Monoallelic amplification of the CA-SSR1 locus was present in 30.6% of the informative cases and occurred more often in individuals of East Asian ethnicity. AI was present in 44.4% (95% confidence interval: 34.1%-54.7%) of mutant tumors compared with 25.9% (20.6%-31.2%) of wild-type tumors (p = 0.002). The shorter allele in tumors with AI in East Asian individuals was selectively amplified (shorter allele dominant) more often in mutant tumors (75.0%, 61.6%-88.4%) than in wild-type tumors (43.5%, 31.8%-55.2%, p = 0.003). In addition, there was a strong positive association between AI ratios of CA-SSR1 alleles and AI of mutant alleles.ConclusionsThe three polymorphisms associated with increased EGFR protein production (shorter CA-SSR1 length and variant forms of SNPs -216 and -191) were found to be rare in East Asians as compared to other ethnicities, suggesting that the cells of East Asians may make relatively less intrinsic EGFR protein. Interestingly, especially in tumors from patients of East Asian ethnicity, EGFR mutations were found to favor the shorter allele of CA-SSR1, and selective amplification of the shorter allele of CA-SSR1 occurred frequently in tumors harboring a mutation. These distinct molecular events targeting the same allele would both be predicted to result in greater EGFR protein production and/or activity. Our findings may help explain to some of the ethnic differences observed in mutational frequencies and responses to TK inhibitors.

Dataset Information

Detection of EGFR gene polymorphisms in non-small cell lung cancer Egyptian patients: a case-control study.

Background

Methods

Results

Conclusions

Publications

Detection of EGFR gene polymorphisms in non-small cell lung cancer Egyptian patients: a case-control study.

Similar Datasets

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