EGFR gene polymorphisms -216G>T and -191C>A are risk markers for gastric cancer in Mexican population

Abstract

ABSTRACT. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with tyrosine-kinase activity that plays an important role in multiple cellular functions. EGFR overexpression has been observed in several types of tumors and it is significantly associated with disease stage, survival, prognosis, and progression of cancer. The polymorphisms -216G>T, -191C>A, and (CA) n first intervening sequence 1803 EGFR polymorphisms and gastric cancer risk ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (1): 1802-1807 (2015) (IVS1) have been related to EGFR overexpression and have been studied in several types of cancer, but not in gastric cancer (GC). The aim of this study was to determine the association of these 3 polymorphisms and GC. Genomic DNA from 68 GC patients and 102 healthy blood donors were analyzed. Polymorphisms were identified by DNA-sequencing (-216G>T and -191C>A) and GeneScan (CA) n IVS1. The results showed that the distribution of the -216G>T and -191C>A genotypes differed between groups (P < 0.05). The odds ratio for the -216TT genotype was 4.59 (95% confidence interval = 1.55-13.54, P < 0.05) and 10.71 (95% confidence interval = 2.31-49.59, P < 0.05) for the -191AA genotype, both in a recessive model. The genotype and allele distributions of the (CA) n IVS1 repeat was similar in both groups. In conclusion, the -216TT and -191AA genotypes and GA haplotype of the EGFR gene were found to be associated with an increased risk of gastric cancer in a Mexican population.

Mutational landscape of gastric adenocarcinoma in Latin America: A genetic approach for precision medicine

“… 40 Moreover, MAPK1 (c.857–3854A > C and c.119 + 21641G > A), RAF1 (c.1669-36C > T) and HRAS (c.-1115T > C) intronic variants increased GA susceptibility on the Chilean population, 45 even when they were initially reported as variables of uncertain significance in ClinVar. Similar disparities between studies were found in Mexican population, where an increased GA susceptibility was associated with the EGFR promotor region variants c.-216G > T, c.-191C > A 49 (related to augmented expression of EGFR protein), the ERBB2 intronic variants c.-18 + 1614C > T, c.-18 + 3073G > T and the missense variant c.3418C > G, 50 classified as variables of uncertain significance in ClinVar. Also, a decreased susceptibility was associated with the TGF-β promoter variant c.-509C > T which is associated with higher TGF-β plasmatic concentration.…”

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

“…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).…”

The Polymorphisms of Epidermal Growth Factor-driven Signaling and Cancer Pathogenesis

“…Both -216G>T and 191 C>A were associated with the risk of developing gastric cancer [20]. -191C/A (rs712830) was also associated with lung cancer [39,40].…”

“…AG/GG rs2237051 (non-synonymous exon region) and AG/GG rs3733625 (3' untranslated region) variants of EGF gene were identified as susceptibility factors in a study conducted on Chinese population [19]. A study based on Mexican population suggested the association of -216G>T, 191C>A polymorphisms of EGFR and the risk of developing gastric cancer [20].…”