A genetic variation in APE1 is associated with gastric cancer survival in a Chinese population

Abstract

Altered DNA repair can be associated with aggressive tumor biology and impact on survival of cancer patients. We investigated whether genetic variation of human apurinic/apyrimidinic (AP) endonuclease, a key multifunctional gene involved in the base excision repair pathway, would play a role in gastric cancer survival outcomes. We genotyped APE1 rs1760944 by the TaqMan method in 925 gastric cancer patients. Analyses of association between the polymorphism and survival outcomes were carried out using the Kaplan-Meier method, Cox proportional hazards models, and the log-rank test. Survival analyses for all patients showed that the differences in median survival time between gastric cancer carriers with APE1 rs1760944 TT (55 months) and those with GT/GG (78 months), were statistically significant (P = 0.025, log-rank test). Kaplan-Meier survival estimates revealed that gastric cancer patients carrying the GT/GG genotypes had a higher survival than TT, and this protective effect was also more pro- A lthough the incidence of gastric cancer has clearly decreased during the past few decades, it still remains one of the most common cancers in the world, and the second most frequent cause of cancer-related death following lung cancer.(1) Many patients have advanced disease at the time of diagnosis, resulting in poor prognosis and worse survival.(2,3) Despite recent advances in early diagnosis and treatment, the 5-year survival rate of gastric cancer still ranges from only 5% to 20%. (4,5) Clinical staging is one available clinical measure of tumor aggression and prognosis, but there are still conspicuous differences even within the same tumor stage. Therefore, it would be useful to improve prognostic accuracy by identifying readily accessible molecular markers that predict some of the variation in clinical outcomes. In recent years, studies had focused on the detection of genetic variants that could play roles in the development and progression of gastric cancer. (6) Base excision repair (BER) for DNA damage, a highly conserved mechanism, has been identified as important for many cancers due to its crucial role in the repair of oxidative and alkylation damage. (7,8) AP endonuclease (APE1) is one of the key genes in short-patch BER. Repair of this DNA damage is initiated by the major AP endonuclease, which specifically recognizes and cleaves the phosphodiester bond on the 5¢-side of the resulting abasic AP site by a hydrolytic mechanism.(9) As the major AP endonuclease in human cells, APE1 (also called HAP1, APEX1, and REF-1), accounts for over 95% of total AP endonuclease activity in most cultured human cell lines. (10,11) As well as its DNA repair activity, APE1 also modulates redox function (11) and transcription. (12,13)

AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

“…The univariate and multivariate analyses showed that 50 cases with APE1 positive expression correlated with short overall survival in patients during follow-up in 24 months ( P = 0.026 and 0.035) (Tables 1 and 2, Figure 1A and 1C). Additionally, we also found that Her-2 overexpression cases has poor prognosis consistent with results from previous study ( P = 0.041 and 0.048) (Tables 1 and 2, Figure 1B and 1C) [16]. To some extent, APE1 and Her-2 overexpression associated with poor outcome of patients with gastric cancer, indicating potential markers for target therapy in clinical settings.…”

DNA Base Excision Repair: Evolving Biomarkers for Personalized Therapies in Cancer

“…Survival analyses showed a statistically significant (P 0.025, log-rank test) differences in median survival time between gastric cancer patients with APE1 rs1760944 TT (55 months) versus those with GT/GG (78 months). These studies suggest that APE1 polymorphism is a potential biomarker in patients with Gastric cancer [56]. In another study, significant differences in the distribution of APE1 genotype were found between colon cancer patients and healthy individuals.…”

A Genetic Polymorphism in TOX3 Is Associated with Survival of Gastric Cancer in a Chinese Population

“…It has been found genetic variant may be a useful marker for predicting the prognosis of patients with gastric cancer. Previous studies reported PSCA rs2294008 and APE1 rs1760944 are associated with gastric cancer survival [5], [6].…”