Epidermal Growth Factor Polymorphism Research Articles

Association between the risk of hepatitis virus-related hepatocellular carcinoma and EGF polymorphism: A PRISMA-compliant updated meta-analysis.

Background:The study aims to provide a comprehensive account of the association between the epidermal growth factor (EGF) + 61A/G polymorphism (rs4444903) and susceptibility to virus-related hepatocellular carcinoma (HCC).Methods:Electronic searching of the Chinese National Knowledge Infrastructure, Wanfang, Chinese Scientific Journal Database (VIP), PubMed, Web of Science, and Embase was conducted to select eligible studies. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to assess the strength of the association.Results:In this study, a total of 18 articles were included with 2692 cases and 5835 controls for assessing the association between rs4444903 and HCC risk. The pooled results showed that the EGF + 61A/G polymorphism was significantly associated with the risk of virus-related HCC in all genetic models. Stratified analyses were conducted based on ethnicity, study quality, source of controls, type of controls, number of cases and genotyping method. The results showed that EGF + 61A/G polymorphisms significantly affect HCC susceptibility in different stratified populations. High heterogeneity was observed across included studies, and meta-regression analysis demonstrated that race, type of controls, and study quality contribute to the observed heterogeneity.Conclusion:This pooled analysis found that EGF + 61A/G polymorphism was significantly associated with the risk of HCC.

Lack of Association between Epidermal Growth Factor or Its Receptor and Reflux Esophagitis, Barrett's Esophagus, and Esophageal Adenocarcinoma: A Case-Control Study.

The epidermal growth factor (EGF) and its receptor (EGFR) gene-gene interactions were shown to increase the susceptibility to esophageal cancer. However, the role of the EGF/EGFR pathway in the development of gastroesophageal reflux disease (GERD) and its complications (reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC)) remains unclear. This association study is aimed at investigating functional EGF and EGFR gene polymorphisms, their mRNA expression in esophageal tissues, and EGF plasma levels in relation to RE, BE, and EAC development in the Central European population. 301 patients with RE/BE/EAC (cases) as well as 98 patients with nonerosive reflux disease (NERD) and 8 healthy individuals (controls) were genotyped for +61 A>G EGF (rs4444903) and +142285 G>A EGFR (rs2227983) polymorphisms using the TaqMan quantitative polymerase chain reaction (qPCR). In random subgroups, the EGF and EGFR mRNA expressions were analyzed by reverse transcription qPCR in esophageal tissue with and without endoscopically visible pathological changes; and the EGF plasma levels were determined by enzyme-linked immunosorbent assay. None of the genotyped SNPs nor EGF-EGFR genotype interactions were associated with RE, BE, or EAC development (p > 0.05). Moreover, mRNA expression of neither EGF nor EGFR differed between samples of the esophageal tissue with and without endoscopically visible pathology (p > 0.05) nor between samples from patients with different diagnoses, i.e., RE, BE, or EAC (p > 0.05). Nevertheless, the lower EGF mRNA expression in carriers of combined genotypes AA +61 EGF (rs4444903) and GG +142285 EGFR (rs2227983; p < 0.05) suggests a possible direct/indirect effect of EGF-EGFR gene interactions on EGF gene expression. In conclusion, EGF and EGFR gene variants and their mRNA/protein expression were not associated with RE, BE or EAC development in the Central European population.

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

Background: Epidermal growth factor (EGF) is a stimulating protein for cell proliferation and differentiation. An amplification of its signaling pathway has been frequently reported in numerous malignant tumors. Specific polymorphisms of the genes encoding proteins involved in this cellular pathway may constitute risk factors for carcinogenesis. The aim of this study was to identify the most relevant polymorphisms of EGF and their signaling pathways and their relation to carcinogenesis.&#x0D; Methods: The study included 40 full-text articles published between January 2010 and May 2020, extracted from PubMed, Scopus, Web of Science, and Science Direct databases in May 2020, using the following keywords: EGF OR epidermal growth factor AND polymorphism AND cancer OR neoplasia OR tumor.&#x0D; Results: We identified relevant polymorphisms of the EGF signaling pathway that were involved in the development and progression of hepatocellular carcinoma, esophageal cancer, gastric cancer, colorectal cancer, glioma, lung cancer, breast cancer, cervical cancer, and head and neck cancer. Rs4444903 variants have been widely studied and the association with numerous tumors has been confirmed by multiple studies. Other frequently investigated polymorphisms are –191C/A and –216G&gt;T.&#x0D; Conclusion: The polymorphisms of EGF signaling pathway have been widely studied in connection to various malignancies. Some predisposing variants are common in different forms of cancer. These polymorphisms might be general risk factors for carcinogenesis.

Association between polymorphisms of epidermal growth factor 61 and susceptibility of lung cancer: A meta-analysis.

To explore the association between epidermal growth factor (EGF) 61A/G polymorphism and lung cancer.All eligible case-control studies published up to August, 2019 were identified by searching PubMed, The excerpta medica database, China Academic Journals Full-text Database, China Biology Medicine, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang databases. Two researchers independently identified the literature, extracted data, and evaluated quality according to inclusion and exclusion criteria. Meta-analysis was performed by Stata 15.0.A total of 6 studies is included, including 1487 cases and 2044 control subjects. Compared with allele A, allele G was considered to have no association with the risk of lung cancer, odds ratio = 1.07 (95% confidence interval: 0.98–1.15). GG recessive genotype, GG + GA dominant genotype, GG homozygote genotype and GA heterozygote genotype were found out that all of them are not associated with the risk of lung cancer. No association between EGF 61A/G polymorphism and lung cancer was found out by ethnical subgroup analysis. However, in view of the limitations of this study, such as the results of quantitative and sensitivity analysis may be lack of accuracy, so the conclusions of allele model and recessive gene model should be made carefully.It suggested that there was no association between polymorphism of EGF 61A/G and susceptibility of lung cancer.

Epidermal Growth Factor Gene Polymorphism in Egyptian Patients with Hepatocellular carcinoma related to Hepatitis C

AIM: Hepatocellular carcinoma (HCC) ranks fifth among the most prevalent cancers worldwide. In Egypt, its incidence has been doubling due to hepatitis C viral (HCV) infection. Epidermal growth factor (EGF) plays an important role in hepatocyte regeneration and had a role in malignant transformation. Single nucleotide polymorphism (SNP) G/G genotype was associated with higher risk for HCC development. This study was done to evaluate the correlation between EGF polymorphism and HCC in patients with HCV. METHODS: Routine investigations for liver cirrhosis and HCC, also EGF genotyping were done on 2 groups; patients with HCV related cirrhosis and patients with newly diagnosed HCC on top of cirrhosis, while the control group performed EGF genotyping only. RESULTS: EGF gene polymorphism 61*G was dominant in HCC patients. The G/G owns the highest concentration when compared with A/A and A/G genotypes, with high statistical significance between the studied groups regarding number and percentage (P < 0.0001). CONCLUSIONS: EGF gene polymorphism 61*G was associated with HCC risk. Moreover, the increased concentration of EGF was associated with G/G genotype.

Association of EGF, IGFBP-3 and TP53 Gene Polymorphisms with Major Depressive Disorder in Slovak Population.

Major depressive disorder (MDD) is a main public health concern worldwide. Despite extensive investigations, the exact mechanisms responsible for MDD have not been identified. Epidermal growth factor (EGF) and insulin growth factor binding protein-3 (IGFBP-3) are involved in brain function. Tumour suppressor protein p53 is widely involved in neuronal death in response to different forms of acute insults and neurological disorders. The present study focuses on the possible associations of the single-nucleotide polymorphisms (SNP) of EGF A61G (rs4444903), IGFBP-3 C32G (rs2854746) and TP53 G72C (rs1042522) genes with MDD risk in the Slovak population. The present case-control association study was carried out in 111 confirmed MDD patients and 207 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. Logistic regression analysis showed no association between SNPs of selected genes and MDD risk in the Slovak population. However, the stratification of individuals by gender revealed that males carrying IGFBP-3 G alleles (G32G or GG) had marginally increased risk for developing MDD as compared to CC homozygous males (p=0.09). In women, inverse association was observed between SNP rs1042522 and MDD risk (p=0.04 for recessive model). Our results suggest the protective effect of minor allele 72C of TP53 gene towards MDD. The disruption of mechanisms involved in cell survival and death regulation may be involved in pathophysiology of MDD.

A Unique Case of Alpha-Fetoprotein-Producing Esophageal Adenocarcinoma

Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but has also been reported in patients with other malignancies, most notably of gastrointestinal origin. However, the organs of origin typically include gastric, pancreatic, and biliary, but rarely esophageal. Here, we report a case of an AFP-producing EAC. A 51 year-old previously healthy man presented with new onset severe acid reflux and a weight loss of 35 pounds over a 2 week duration. He also endorsed 2 days of non-bloody emesis, but denied dysphagia or regurgitation of undigested food. Physical exam was only remarkable for right upper quadrant tenderness. The patient was slightly anemic with a hemoglobin of 12.8 g/dL. Elevated labs included: AST 66 U/L, ALT 81 U/L, CEA 6.4 ug/L, CA 19-9 317443 U/mL, and AFP 2524 ng/mL. Hepatitis B surface antigen and hepatitis C antibody were non-reactive. Computed tomography (CT) scan of the abdomen revealed abnormal thickening of the esophagus and multiple masses throughout the liver consistent with metastatic disease. CT-guided biopsy of one of the masses revealed CDX-2 positive adenocarcinoma, suggesting gastrointestinal origin. Subsequent upper endoscopy revealed a large, partially-obstructing mass in the lower third of the esophagus, the assumed primary source. Biopsy of the mass revealed ulcerated glandular mucosa with high grade dysplasia, with likely underlying malignancy. One month later, the patient underwent palliative esophageal stent placement. He was scheduled to begin FOLFOX/Herceptin therapy, but expired a week later. EAC is typically found in the lower third of the esophagus, and is associated with Barrett's esophagus, smoking, obesity, and epidermal growth factor polymorphisms. A previous study attempting to determine possible tumor markers in patients with esophagus cancer reported serum AFP levels >5 ng/mL in up to 18% of EACs, with the highest reported AFP level being 320ng/mL. However, to the best of our knowledge, our case is only the 14th AFP-producing EAC to be thoroughly described in the English literature. Patients with EAC and cirrhosis often share common risk factors that make the differential diagnosis of liver masses and elevated AFP challenging. Some AFP-producing EACs contain cells resembling hepatic cells and are termed hepatoid EAC. Although not possible in our case, serial measurement of serum AFP level may be useful for monitoring clinical status and response to treatment. Most cases are treated with surgery and adjuvant chemotherapy but with disappointing results given the advanced presenting stage, high liver metastatic potential, and poor prognosis of AFP-producing EAC.Figure 1Figure 2Figure 3

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

BackgroundEpidermal growth factor (EGF) and its receptor (EGFR) are part of an important signaling pathway that is involved in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that EGF/EGFR genetic polymorphisms might have a prognostic impact on disease-free survival and overall survival (OS) in locally advanced SCCHN.Materials and methodsThe patient group included a consecutive cohort of 180 patients with locally advanced SCCHN who underwent postoperative concurrent chemoradiotherapy between 2002 and 2010. DNA from formalin-fixed, paraffin-embedded tumor tissues was genotyped for the single nucleotide polymorphism (SNP) of EGF A61G A>G, EGFR R521K G>A and G-216T. The log-rank test was applied to evaluate the impact of SNPs on the outcomes. Survival was estimated using the Kaplan–Meier statistical method.ResultsWe demonstrated that EGF/EGFR SNPs might predict prognosis in patients with primary pharyngolaryngeal tumors, but not in those with oral cavity tumors. In pharyngolaryngeal tumor subgroup, EGF61 G/G genotype led to worse 5 year OS rate when compared to G/A or A/A genotypes (13.3% versus 34.3% versus 50.0%, P=0.017). The 5 year OS of patients with EGFR R521K G/G (11.1%) and G/A (15.9%) were lower than the A/A (62.5%) genotype (P=0.054). Patients carrying one or two unfavorable alleles had worse 5 year OS than those without unfavorable allele (not available versus 20% versus 71.4%, P=0.002). Multivariate analysis revealed that the highest risk of death was associated with the coexistence of two unfavorable genotypes (hazard ratio 25.7, 95% confidence interval =3.4–193.4; P=0.002).ConclusionIn this study, we were able to demonstrate that the EGF A61G and EGFR R521K genetic polymorphisms might be important prognostic factors in patients with locally advanced primary pharyngolaryngeal squamous cell carcinoma who underwent postoperative concurrent chemoradiotherapy.

P04.11 * GENETIC POLYMORPHISMS OF EGF 5'-UTR IN PATIENTS WITH GLIOMA: A POSSIBLE PREDICTIVE MARKER OF OUTCOME

BACKGROUND: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer outcome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. METHODS: The significant SNP rs4444903, EGF 61A/G, was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. RESULTS: We investigated EGF +61G/A polymorphism in 28 glioma patients. EGF +61G allele has been found in 68% of glioma patients (22% G/G genotype and 46% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 73% and 54%. In WHO IV gliomas, the EGF +61G allele represents a 72% frequency, (27% G/G and 45% A/G ), in WHO III gliomas a 81% frequency (54% G/G and 27% A/G ) and in WHO II gliomas a 33% frequency (80% A/G ). Median PFS of glioblastoma patients was 9 months. 79% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. CONCLUSIONS: Our data confirm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.

EGF rs11568835 G/A polymorphism is associated with increased risk of rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune rheumatological disease thought to have substantial genetic contributions. Epidermal growth factor (EGF) can activate DNA synthesis and cellular proliferation. Early RA synovial fluid was characterized by significantly elevated levels stromal cell and macrophage-related cytokines including EGF. We therefore hypothesized that EGF polymorphisms may contribute to RA susceptibility in the Chinese population. We studied EGF rs11568835 G/A and EGF rs3756261 T/C polymorphisms in 520 patients with RA and 520 controls in a Chinese population. When the EGF rs11568835 GG homozygote genotype was used as the reference group, the AA genotype was associated with an increased risk for RA (AA versus GG, odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.19–11.17, p = 0.024), the GA or GA/AA genotype was not associated with the risk for RA (GA versus GG, OR = 0.99, 95% CI = 0.75–1.31, p = 0.931; GA + AA versus GG, OR = 1.06, 95% CI = 0.81–1.40, p = 0.659). EGF rs3756261 T/C was not associated with susceptibility to RA. These results provide the first positive evidence for an association between EGF rs11568835 G/A polymorphism and RA.

Association between EGF and VEGF functional polymorphisms and sporadic colorectal cancer in the Malaysian population.

Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allele-specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made.

Different frequency of epidermal growth factor rs76189946 polymorphism genotype in Iranian colorectal cancer patients

Aim : This study aimed to determinant association between rs76189946 polymorphism of EGF gene and risk of colorectal cancer in an Iranian population. Background : Colorectal cancer (CRC) is the third most prevalent cancer in both genders worldwide. The determination of genetic variation becomes a new way to etiology of colorectal cancer. Epidermal growth factor (EGF) is a mitogen that plays an important role in cell growth and tumourigenesis, this protein acts by binding its receptor, EGFR. Patients and methods : DNA samples taken from totally 125 CRC patients and healthy controls were amplified by polymerase chain reaction (PCR) for the rs76189946 polymorphism. Genotypes were analyzed using restriction fragment length polymorphism (RFLP). Finally to confirm the RFLP procedure, 20 of the PCR products were sequenced using the ABI PRISM 3130xl Genetic Analyzer and chain termination method (Applied Biosystems, Carlsbad, CA). Results : Genotype distribution and allele frequency was similar in CRC patients and controls individuals. We expect observe C and G allele in both groups but only was found C allele. Conclusion : In this study for first time we identified genetic distribution of exonic rs76189946 polymorphism in EGF gene both CRC patients and healthy controls. These results suggest there wasn’t association between EGF polymorphism rs76189946 and risk of colorectal cancer in an Iranian population.

Genetic polymorphisms of EGF 5'-UTR in patients with glioma: A possible predictive marker of outcome.

e13009 Background: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer otucome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. Methods: EGF 61A/G polymorphism (rs4444903) was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method (GenBank reference sequence-accession no. AC005509) from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. Results: We investigated EGF +61G/A polymorphism in 24 glioma patients . EGF +61G allele has been found in 67% of glioma patients (25% G/G genotype and 42% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 71% and 50%. In WHO IV gliomas, the EGF +61G allele represents a 63% frequency, (27% G/G and 36% A/G ), in WHO III gliomas a 77% frequency (33% G/G and 44% A/G ) and in WHO II gliomas a 50% frequency (100% A/G ). Median PFS of glioblastoma patients was 9 months. 83% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. Conclusions: Our data conferm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.

Genetic polymorphisms of epidermal growth factor in relation to risk of hepatocellular carcinoma: two case-control studies.

BackgroundEarlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A > G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk.MethodsThe EGF 61A > G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China.ResultsFollowing adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR) = 3.44, 95% confidence interval (CI) = 0.93–12.76, P = 0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR = 3.34, 95% CI = 1.24-9.03, P = 0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China.ConclusionGenetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.

The effect of 5'untranslated region polymorphism in EGF gene, rs4444903, on colorectal cancer.

The purpose of this study was to determine the relationship of rs4444903 (EGF+61A/G) SNP genotype with colorectal cancer and tumor stage in an Iranian population. Epidermal growth factor (EGF) is one of the important proteins that determine survival of cells. EGF binds to its receptor on the cell surface and then activates some of the cell signaling pathway networks within cells that lead to activation or deactivation of factors which are responsible for growth and apoptosis of cells. In this study we assessed the association in EGF polymorphism rs4444903 with colorectal cancer (CRC) in Iranian population. We conducted case-control study to investigate the association of polymorphism rs4444903 in EGF, with colorectal cancer risk in Iranian population. Analyzed Polymorphism of EGF rs4444903 with restriction fragment length polymorphisms (RFLP) among two groups of subjects consisting of including 220 cases with colorectal cancer and 220 healthy individuals as controls. Mutations were confirmed in 10% of the samples by direct sequencing. The frequencies of AA, AG and GG genotypes among cases with colorectal cancer were 28.2, 46.8, and 25.0 % respectively and in controls genotype frequencies were 23.2, 56.4, and 20.5 %, respectively. Frequency of A allele among case group was 51.6% and for control group was 51.4%. The frequency of G allele in case and control was, respectively 48.4% and 48.6% (OR= 1.009, 95% CI= 0.775-1.315; P= 0.946). The percentage of Stage 0, I, II, III, IV were 5%, 9.35%, 38.84%, 30.21% and 16.54%, respectively, among the cases. However, no significant association between this polymorphism and CRC stage was observed (p=0.626). Our data suggest a SNP rs4444903 may not represent a risk factor in the development and progression of CRC among Iranian population.

Clarification of Data for a Recent Meta-Analysis—Epidermal Growth Factor Polymorphisms and Cancer Risk: Involving 9,779 Cases and 15,932 Controls

Clarification of Data for a Recent Meta-Analysis—Epidermal Growth Factor Polymorphisms and Cancer Risk: Involving 9,779 Cases and 15,932 Controls

Genetic polymorphisms of EGF 5'-UTR and NAT2 857G/A associated with glioma in a case control study of Malaysian patients

Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma.

Meta-Analysis of Epidermal Growth Factor Polymorphisms and Cancer Risk: Involving 9,779 Cases and 15,932 Controls

The epidermal growth factor (EGF) pathway stimulates proliferation and differentiation of epidermal and epithelial tissues, and plays an important role in tumorigenesis. The association between EGF polymorphisms and cancer risk is controversial; thus, we performed this meta-analysis. Overall, 41 case-control studies with 9,779 cases and 15,932 controls were retrieved. We found that EGF +61A/G polymorphism increased overall cancer risk (G allele vs. A allele: OR=1.181, 95% CI=1.077-1.295, P(heterogeneity) < 0.001; GG vs. AA: OR=1.370, 95% CI=1.143-1.641, P(heterogeneity) < 0.001; GG+GA vs. AA: OR=1.175, 95% CI=1.047-1.318, P(heterogeneity) < 0.001). In the stratified analysis by cancer type, the +61 G allele was a risk factor for colorectal cancer, esophageal carcinoma, gastric cancer, and hepatocellular carcinoma. Individuals who carried +61G allele had higher cancer susceptibility in mixed and European racial subgroups. An increased association was detected in the hospital-based subgroup. No significant association was found among EGF -1380A/G, -1744G/A, rs6983267T/G polymorphisms and cancer risk.

Genetic Variations in Angiogenesis Pathway Genes Predict Tumor Recurrence in Localized Adenocarcinoma of the Esophagus

The aim of this study was to determine whether the risk of systemic disease after esophagectomy could be predicted by angiogenesis-related gene polymorphisms. Systemic tumor recurrence after curative resection continues to impose a significant problem in the management of patients with localized esophageal adenocarcinoma (EA). The identification of molecular markers of prognosis will help to better define tumor stage, indicate disease progression, identify novel therapeutic targets, and monitor response to therapy. Proteinase-activated-receptor 1 (PAR-1) and epidermal growth factor (EGF) have been shown to mediate the regulation of local and early-onset angiogenesis, and in turn may impact the process of tumor growth and disease progression. We investigated tissue samples from 239 patients with localized EA treated with surgery alone. DNA was isolated from formalin-fixed paraffin-embedded normal esophageal tissue samples and polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism and 5'-end [gamma-P] ATP-labeled polymerase chain reaction methods. PAR-1 -506 ins/del (adjusted P value=0.011) and EGF +61 A>G (adjusted P value=0.035) showed to be adverse prognostic markers, in both univariate and multivariable analyses. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of PAR-1 -506 ins/del (any insertion allele) and EGF +61 A>G (A/A) were associated with a higher likelihood of developing tumor recurrence (adjusted P value<0.001). This study supports the role of functional PAR-1 and EGF polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence.

Genetic variations in EGF and EGFR and glioblastoma outcome

Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete tagging of the epidermal growth factor (EGF) and EGF receptor (EGFR) gene polymorphisms as potential prognostic factors. Thirty tagging single-nucleotide polymorphisms (SNPs) in EGF and 89 tagging SNPs in EGFR were analyzed for association with survival in 176 glioblastoma cases. Validation analyses were performed for 4 SNPs in a set of 638 glioblastoma patients recruited at The University of Texas M. D. Anderson Cancer Center (MDACC). Three hundred and seventy-four glioblastoma patients aged 50 years or older at diagnosis were subanalyzed to enrich for de novo arising glioblastoma. We found 7 SNPs in haplotype 4 in EGF that were associated with prognosis in glioblastoma patients. In EGFR, 4 of 89 SNPs were significantly associated with prognosis but judged as false positives. Four of the significantly associated EGF polymorphisms in haplotype block 4 were validated in a set from MDACC; however, none of the associations were clearly replicated. rs379644 had a hazard ratio (HR) of 1.19 (0.94–1.51) in the whole population with 18.6 months survival in the risk genotype compared with 24.5 in the reference category. As the median age differed slightly between the 2 study sets, the MDACC cases aged 50 or older at diagnosis were analyzed separately (rs379644, HR 1.32 [0.99–1.78]), which is marginally significant and partially validates our findings. This study is, to our knowledge, the first to perform a comprehensive tagging of the EGF and EGFR genes, and the data give some support that EGF polymorphisms might be associated with poor prognosis. Further confirmation in independent data sets of prospective studies is necessary to establish EGF as prognostic risk factor.