Association between epidermal growth factor gene +61A/G polymorphism and the risk of hepatocellular carcinoma: a meta-analysis based on 16 studies

Abstract

BackgroundThe association between epidermal growth factor (EGF) gene +61A/G polymorphism (rs4444903) and hepatocellular carcinoma (HCC) susceptibility has been widely reported, but the results were inconsistent. To clarify the effect of this polymorphism on HCC risk, a meta-analysis was performed.MethodsThe PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature (CBM), Wanfang and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies published up to December 2013. Data were extracted independently by two authors. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of association.ResultsA total of 16 studies including 2475 HCC cases and 5381 controls were included in this meta-analysis. Overall, a significantly increased HCC risk was observed under all genetic models (G vs. A: OR = 1.383, P < 0.001, 95% CI: 1.174-1.629; GG vs. GA + AA: OR = 1.484, P < 0.001, 95% CI: 1.198-1.838; GG + GA vs. AA: OR = 1.530, P < 0.001, 95% CI: 1.217-1.924; GG vs. AA: OR = 1.958, P < 0.001, 95% CI: 1.433-2.675; GA vs. AA: OR = 1.215, P = 0.013, 95% CI: 1.041-1.418). In the subgroup analyses by ethnicity, a significant association with HCC risk was found in Asian populations (G vs. A: OR = 1.151, P = 0.001, 95% CI: 1.056-1.255), European populations (G vs. A: OR = 1.594, P = 0.027, 95% CI: 1.053-2.413, and African populations (G vs. A: OR = 3.599, P < 0.001, 95% CI: 2.550-5.080), respectively.ConclusionsOur study shows that EGF +61A/G polymorphism is significantly associated with the increased HCC risk, especially in Asian populations. Further large-scale and well-designed studies are required to confirm this conclusion.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1318-6) contains supplementary material, which is available to authorized users.

The Relationships between Polymorphisms in Genes Encoding the Growth Factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A and the Restenosis Process in Patients with Stable Coronary Artery Disease Treated with Bare Metal Stent

“…EGF may influence restenosis primarily through SMC migration to the vessel lumen because an EGF receptor antagonist inhibited SMC migration but not proliferation [ 51 ]. A relationship between rs4444903 and a risk of development and malignancy of numerous neoplastic diseases was demonstrated [ 20 , 52 , 53 ], thus confirming its “functionality”. Our study is the first to examine the relationship between this polymorphism and restenosis, but no relationship between rs4444903 and the intensity of this process was identified.…”

“…The rs308395 polymorphism within the bFGF gene promoter may influence transcription factors binding, and thus bFGF expression [ 18 , 19 ]. The rs4444903 polymorphism (A61G) within the EGF gene promoter region is associated with EGF levels and various neoplastic diseases [ 20 , 21 ]. The rs699947 polymorphism of the VEGF-A gene is associated with a higher risk of developing certain neoplastic diseases [ 22 ] and, in cardiology, with the development of collateral circulation [ 23 ] or a response to anti-hypertensive therapy [ 24 ].…”

Impact of clinically significant portal hypertension on outcomes after partial hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis

“…In addition, as HCC developed from different areas might have different clinicopathological characteristics and different racial descent, 41 different geographical area was also used as an additional factor in the stratified meta-analysis. [42][43][44] Our meta-analysis showed that presence of CSPH significantly decreased the short-and long-term outcomes when compared with patients without CSPH. According to the BCLC staging system, 6 surgical resection is contraindicated in HCC patients with CSPH and elevated bilirubin level, which has also been adopted by the AASLD and the EASL guidelines and consistent with the current international guidelines.…”

The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease

“…Studies on primates have shown that a high-cholesterol diet leads to activation of signal pathways associated with EGF [26]. Similarly, as is the case for rs308395 in the FGF2 gene, rs444903 is associated with the course of many cancers, including lung cancer [27–29]. Despite the role of EGF in atherosclerosis, our paper is the first to assess the association of the known functional polymorphism rs444903 with the severity of coronary atherosclerosis.…”