Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer.

Ovarian cancer (OC) is the deadliest gynecological cancer in women. Immune cell infiltration has a critical role in regulating carcinogenesis and prognosis in OC. To identify prognostic genes relevant to the tumor microenvironment in OC, we investigated the association between OC and gene expression profiles. Results obtained with the ESTIMATE R tool showed that immune score and stromal score were correlated with lymphatic invasion, and high immune score predicted a favorable prognosis. A total of 342 common differentially expressed genes were identified according to the two scores; these genes were mainly involved in immune response, extracellular region, and serine-type endopeptidase activity. Three immune-related prognostic genes were selected by univariate and multivariate Cox regression analysis. We further established a prognostic model and validated the prognostic value of three hub genes in different databases; our results showed that this model could accurately predict survival and evaluate prognosis independent of clinical characteristics. Three hub genes have prognostic value in OC. TIMER analysis revealed that the three genes were correlated with different immune cells. Low levels of macrophage infiltration and high levels of CD4+ T cell infiltration were associated with favorable survival outcomes. Arm-level gain of GYPC was correlated with neutrophils and dendritic cells. These findings indicate that CXCR4, GYPC, and MMP12 modulate prognosis via effects on the infiltration of immune cells. Thus, these genes represent potential targets for immune therapy in OC.

Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature.

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected via calculating Pearson's correlation coefficient. Three prognosis-related autophagy lncRNAs were identified via univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed via analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients.

Saikosaponin-d Increases the Radiosensitivity of Hepatoma Cells by Adjusting Cell Autophagy.

Radiotherapy for liver cancer can affect the level of autophagy in cells, and effective autophagy regulation can increase the radiosensitivity of liver cancer cells.Saikosaponin-d (SSd) is an effective active ingredient extracted from traditional Chinese medicine Bupleurum. We have confirmed previously in vitro and in vitro experiments that SSd can significantly induce apoptosis of liver cancer cells, increase the radiosensitivity of liver cancer cells.This study explored the role of autophagy in SSd-mediated radiosensitivity of liver cancer cells. MTT and clone formation experiments showed that radiation can inhibit the proliferation of hepatoma cells and reduce the colony formation of hepatoma cells. After the addition of SSd, the inhibitory effect of radiation on the proliferation and clonal formation of hepatoma cells was further enhanced. However, the addition of the autophagy inhibitor chloroquine or mTOR agonist can partially reverse the inhibitory effect of the combined treatment of SSd with radiation on the proliferation of hepatoma cells. Similarly, transmission electron microscopy and laser confocal microscopy showed that after the addition of SSd, the number of radiation-induced autophagosomes increased significantly in hepatoma cells and the intervention of mTOR agonist can reduce the formation of autophagosomes in hepatoma cells.In addition,Western blot analysis presented that radiation significantly increased LC3-II levels. Especially when SSd is added, LC3-II levels is further increased. Our data indicate that SSd can inhibit the growth of liver cancer cells and enhance cell radiosensitivity by inducing autophagy formation.

Predictive Value of UGT1A1*28 Polymorphism In Irinotecan-based Chemotherapy.

The UGT1A1*28 polymorphism was suggested to be significantly connected with irinotecan-induced toxicity and response to chemotherapy. However, the results of previous studies are controversial. Hence we carried out a meta-analysis to investigate the effect of UGT1A1*28 polymorphism on severe diarrhea, neutropenia, and response of patients who had undergone irinotecan-based chemotherapy. The PubMed, Web of Science, Wanfang, and CNKI databases were searched for clinical trials assessing the association of UGT1A1*28 polymorphism with severe diarrhea, neutropenia, and response to irinotecan-based chemotherapy. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship under a fixed- or random-effects model. Fifty-eight studies including 6087 patients with cancer were included. Our results showed that patients carrying the TA6/7 and TA7/7 genotypes had a greater prevalence of diarrhea and neutropenia than those with the TA6/6 genotype (TA6/7+TA7/7 vs. TA6/6: diarrhea, OR = 2.18, 95%CI = 1.68-2.83; neutropenia, OR = 2.15, 95%CI = 1.71-2.70), particularly patients with metastatic colorectal cancer. Stratified analysis showed that Asians with the TA6/7 and TA7/7 genotypes were more likely to have diarrhea and neutropenia, and Caucasians with the TA6/7 and TA7/7 genotypes were more likely to have neutropenia than other groups. However, patients with the TA6/7+TA7/7 genotypes showed a higher response than patients with TA6/6 genotype (OR = 1.20, 95%CI = 1.07-1.34), particularly Caucasians (OR = 1.23, 95%CI = 1.06-1.42) and patients with metastatic colorectal cancer (OR = 1.24, 95%CI = 1.05-1.48). Our data showed that the UGT1A1*28 polymorphism had a significant relationship with toxicity and response to irinotecan-based chemotherapy. This polymorphism may be useful as a monitoring index for cancer patients receiving irinotecan-based chemotherapy.

Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population.

Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.

MiR-146a and miR-196a-2 polymorphisms are associated with hepatitis virus-related hepatocellular cancer risk: a meta-analysis.

Previous studies have investigated the role of miR-146a rs2910164 and miR-196a-2 rs11614913 polymorphisms in hepatocellular carcinoma (HCC) susceptibility, but the results are contradictory and few specifically studied hepatitis virus-related HCC. Therefore, we conducted a meta-analysis to evaluate the association between these two polymorphisms and hepatitis virus-related HCC risk. We performed a systematical search in EMBASE, PubMed, Web of Science, CNKI and Wanfang databases as of 25th November, 2016. Finally, we assessed 14 studies involving 3852 cases and 5275 controls. Our results suggest that rs2910164 has a significant association with increased hepatitis virus-related HCC risk in allelic, homozygous, heterozygous, and dominant models (CG+GG vs. CC: OR=1.22, 95% CI=1.06-1.39, P=0.004), particularly in Chinese and HBV-related HCC subgroups. Conversely, rs11614913 was associated with lower hepatitis virus-related HCC risk in the overall analysis under allelic (T vs. C: OR=0.85, 95% CI=0.74-0.98, P=0.02), homozygous, dominant and recessive models. Subgroup analyses showed decreased risk in Chinese, HBV- and HCV-related HCC. In conclusion, miR-146a C>G (rs2910164) can increase HBV-related HCC risk while miR-196a-2 C>T (rs11614913) may decrease the risk of HBV- and HCV-related HCC, especially in the Chinese population. Further, large-scale studies including other races are required to confirm these findings.

Lack of Association Between Polymorphisms in AGT and ATR1 and IgA Nephropathy in a Chinese Population.

OBJECTIVE: The mechanism of immunoglobulin A nephropathy (IgAN) remains unclear. Genetic factors may be associated with the risk of IgAN. This study aims to identify the possible association of M268T (rs699) in the Angiotensinogen (AGT) gene and A1166C (rs5186) in the Angiotensin II receptor type 1 (ATR1) gene with IgAN risk. METHODS: Study subjects included 351 patients with IgAN and 310 controls from the Chinese population. The tag SNPs (tSNPs) were genotyped by Sequenom MassARRAY RS1000. Statistical analysis of the association between tSNPs and IgAN was performed using the χ(2) test and SNPStats software. RESULTS: The AGT (M268T) genotypes were distributed in IgAN as CC 61.9%, CT 34.8%, and TT 3.2%, while in controls CC 64.1%, CT 31.3%, and TT 4.6%. Distribution of ATR1 (A1166C) was AA 87.7%, CA 12.3%, and CC 0%, while in controls AA 87.2%, CA 12%, and CC 0.8%. We further analyzed tSNPs under different inheritance models and found that there were no significant differences in the genotypes and allele frequencies of rs699 and rs5186 between two groups (p > 0.05). We also analyzed tSNPs based on the rate of pressure, proteinuria and Lee's classification, and no significant differences were found in the models (p > 0.05). CONCLUSION: rs699 in the AGT gene and rs5186 in the ATR1 gene were not associated with the risk and clinical outcomes of IgAN.

Current evidence on the relationship between two common polymorphisms in NPAS2 gene and cancer risk.

The relationship between neuronal PAS domain protein 2 (NPAS2) gene polymorphisms and cancer risk has been widely investigated. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation on the relationship. We searched Pubmed, and Web of Knowledge databases until Dec, 2014 to identify eligible studies. Case-control studies containing available genotype frequencies of the NPAS2 polymorphisms were chosen. The odds ratios (ORs) with 95% confidence interval (CI) were used to assess the strength of association. Eight independent case-control studies with 3,857 cancer patients and 4,525 cancer-free controls were selected for this meta-analysis. Two NPAS2 gene polymorphisms were identified (rs2305160 and rs17024926). The results showed statistically significant associations of rs2305160 with cancer risk (AA+GA vs. GG: OR = 0.84, 95% CI = 0.72-0.98, P = 0.02; AG vs. GG: OR = 0.81, 95% CI = 0.68-0.96, P = 0.02). Stratified analysis by cancer type indicated that rs2305160 may decrease the risk of breast cancer (A vs. G: OR = 0.87, 95% CI = 0.76-0.96, P = 0.006; AA+GA vs. GG: OR = 0.77, 95% CI = 0.67-0.88, P<0.001; AG vs. GG: OR = 0.74, 95% CI = 0.64-0.86, P<0.001), whereas negative results were obtained for prostate cancer. For rs17024926 polymorphism, there was no significant association in any genetic model. This meta-analysis suggests that NPAS2 rs2305160 polymorphism may reduce cancer susceptibility, especially in breast cancer.

Quantitative Assessment of the Association between Genetic Variants in MicroRNAs and Colorectal Cancer Risk.

BACKGROUND: The associations between polymorphisms in microRNAs and the susceptibility of colorectal cancer (CRC) were inconsistent in previous studies. This study aims to quantify the strength of the correlation between the four common polymorphisms among microRNAs (hsa-mir-146a rs2910164, hsa-mir-149 rs2292832, hsa-mir-196a2 rs11614913, and hsa-mir-499 rs3746444) and CRC risk. METHODS: We searched PubMed, Web of Knowledge, and CNKI to find relevant studies. The combined odds ratio (OR) with 95% confidence interval (95% CI) was used to estimate the strength of the association in a fixed or random effect model. RESULTS: 15 studies involving 5,486 CRC patients and 7,184 controls were included. Meta-analyses showed that rs3746444 had association with CRC risk in Caucasians (OR = 0.57, 95% CI = 0.34-0.95). In the subgroup analysis, we found significant associations between rs2910164 and CRC in hospital based studies (OR = 1.24, 95% CI = 1.03-1.49). rs2292832 may be a high risk factor of CRC in population based studied (OR = 1.18, 95% CI = 1.08-1.38). CONCLUSION: This meta-analysis showed that rs2910164 and rs2292832 may increase the risk of CRC. However, rs11614913 polymorphism may reduce the risk of CRC. rs3746444 may have a decreased risk to CRC in Caucasians.

Relationship between apurinic endonuclease 1 Asp148Glu polymorphism and gastrointestinal cancer risk: An updated meta-analysis.

AIM: To evaluate the relationship between apurinic endonuclease 1 (APE1) Asp148Glu polymorphism and the susceptibility to gastrointestinal (GI) cancers. METHODS: We searched PubMed, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure (CNKI) databases updated on July 15, 2014 for relevant studies. Only case-control studies comparing APE1 Asp148Glu polymorphism and GI cancer risk were included. We excluded studies reporting only standardized incidence ratios without control groups and those without detailed genotyping data. Meta-analysis was performed on 17 studies involving 4856 cancer patients and 6136 cancer-free controls. Review Manager version 5.1 was used to perform the meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated under the allele contrast, homozygous, heterozygous, dominant and recessive genetic models. We also conducted subgroup analyses stratified by ethnicity and cancer type. Publication bias was evaluated using Begg's test. RESULTS: The meta-analysis showed a significant association between APE1 Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall population (G vs T: OR = 1.18; 95%CI: 1.05-1.32; TG vs TT: OR = 1.28; 95%CI: 1.08-1.52; TG + GG vs TT: OR = 1.32; 95%CI: 1.10-1.57). Stratified analysis by ethnicity revealed a statistically increased GI cancer risk in Asians (G vs T: OR = 1.27; 95%CI: 1.07-1.51; GG vs TT: OR = 1.58; 95%CI: 1.05-2.38; TG vs TT: OR = 1.30; 95%CI, 1.01- 1.67; and TG + GG vs TT: OR = 1.38; 95%CI: 1.07-1.78), but not in Caucasians. Further subgroup analysis by cancer type indicated that APE1 Asp148Glu polymorphism may contribute to gastric cancer risk. However, Asp148Glu has no significant association with colorectal or esophageal cancer risk in any genetic model. CONCLUSION: This meta-analysis suggests that the APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk, especially in gastric cancer.

Effects of PSCA rs2294008 (C/T) and c-MYC rs9642880 (G/T) polymorphisms on bladder cancer: evidence from a meta-analysis.

Previous studies have investigated the associations between the two polymorphisms (prostate stem cell antigen (PSCA) rs2294008 C/T and c-MYC rs9642880 G/T) and bladder cancer (BC) risk. However, the results are inconsistent. We therefore carried out a meta-analysis to estimate the relationship between PSCA/c-MYC polymorphisms and BC risk. We searched PubMed up to November 2014 to identify potentially eligible literatures. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations, the data were further stratified by ethnicity. Heterogeneity was evaluated by Q test and I(2) statistics. Begg's funnel plot and Egger's test were used to assess the publication bias. 11 studies from 9 articles were identified, including a total of 16,814 cancer cases and 52,868 case-free controls. We found a significant association between PSCA rs2294008 polymorphism and BC risk (the allele contrast model: OR = 1.14, 95% CI = 1.11-1.18; homozygote comparison: OR = 1.28, 95% CI = 1.20-1.37; heterozygote comparison: OR = 1.23, 95% CI = 1.17-1.30; dominant model: OR = 1.25, 95% CI = 1.19-1.31 and recessive model: OR = 1.13, 95% CI = 1.07-1.20). Moreover, a significant increased risk of BC was confirmed both in Caucasian and in Asians. For c-MYC rs9642880 polymorphism, significant increased BC risk was detected under the following genetic models (the allele contrast model: OR = 1.20, 95% CI = 1.13-1.27; homozygote comparison: OR = 1.37, 95% CI = 1.21-1.55; heterozygote comparison: OR = 1.20, 95% CI = 1.09-1.32; dominant model: OR = 1.25, 95% CI = 1.14-1.37 and recessive model: OR = 1.26, 95% CI = 1.13-1.40). Further stratified analysis by ethnicity also observed the same results. This meta-analysis suggested that PSCA rs2294008 and c-MYC rs9642880 polymorphisms may increase the BC risk. Further studies are needed to clarify the effects.

PSCA rs2294008 C > T polymorphism contributes to gastric and bladder cancer risk.

BACKGROUND: Previous studies suggested genetic variations in PSCA (prostate stem cell antigen) may confer the susceptibility of cancer. Many case-control studies have reported the relationship between PSCA rs2294008 C > T polymorphism and cancer, especially gastric cancer and bladder cancer. However, the results are inconsistent. This meta-analysis is aimed at evaluating the association of rs2294008 polymorphism with cancer risk. METHODS: The databases of PubMed, ISI Web of Knowledge, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for related publications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Fixed models were used when heterogeneity among studies was not detected, otherwise the random model was used. RESULTS: Twenty-six studies from 24 articles with 30,050 multiple cancer cases and 51,670 controls were pooled into this meta-analysis. The results showed that the rs2294008 polymorphism was associated with increased cancer risk in any genetic model (T vs C, OR: 1.18, 95% CI: 1.08-1.28; TT vs CC, OR: 1.36, 95% CI: 1.14-1.62; TC vs CC, OR: 1.29, 95% CI: 1.17-1.44; TT + TC vs CC, OR: 1.32, 95% CI: 1.18-1.49; TT vs TC + CC, OR: 1.15, 95% CI: 1.02-1.30). In stratified analysis by cancer type, we found that the T allele had a significant high risk of gastric and bladder cancer, but not in other cancers. In subgroup analysis by ethnicity, increased cancer risk was found in both Asians and Caucasians. CONCLUSION: Our study suggested that the PSCA rs2294008 C > T polymorphism is a risk factor for cancer, especially in gastric and bladder cancer.

Association between MDM2 rs 2279744 polymorphism and breast cancer susceptibility: a meta-analysis based on 9,788 cases and 11,195 controls.

PURPOSE: Previous studies have suggested associations between MDM2 (mouse double minute 2 homolog) polymorphisms and cancer risk. The aim of this study was to evaluate the relationship between the MDM2 rs 2279744 polymorphism and the susceptibility of breast cancer. METHODS: We searched PubMed, Web of Knowledge, Embase, and the Chinese National Knowledge Infrastructure (CNKI) database for case-control studies published up to October 2013 that investigated MDM2 rs 2279744 polymorphism and breast cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of these associations. RESULTS: A total of 19 studies were identified for the meta-analysis, including 9,788 cases and 11,195 controls. The variant heterozygote (TG) was associated with breast cancer risk in the overall population (TG vs TT: OR =1.10, 95% CI =1.04-1.17, P=0.001, P=0.23 for heterogeneity test). In the subgroup analyses by ethnicity, a significantly increased risk was observed among Asians (G vs T: OR =1.12, 95% CI =1.02-1.23, P=0.02, P het=0.04; GG vs TT: OR =1.29, 95% CI =1.06-1.56, P=0.01, P het=0.04; TG vs TT: OR =1.36, 95% CI =1.15-1.60, P=0.0004, P het=0.45; dominant model TG+GG vs TT: OR =1.21, 95% CI =1.03-1.41, P=0.02, P het=0.07). However, among Caucasians, rs 2279744 was associated with breast cancer risk in only one genotype (TG vs TT: OR =1.09, 95% CI =1.00-1.18, P=0.04, P het=0.37). No publication bias was found in the present study. CONCLUSION: This meta-analysis provides evidence for the association between the MDM2 rs 2279744 polymorphism and breast cancer susceptibility. The results suggest that the MDM2 rs 2279744 polymorphism plays an important role in breast cancer, especially in Asians.

Effects of interleukin-10 polymorphisms (rs1800896, rs1800871, and rs1800872) on breast cancer risk: evidence from an updated meta-analysis.

BACKGROUND: The associations between Interleukin-10 (IL-10) polymorphisms and breast cancer (BC) risk are inconsistent. This study was aimed to evaluate the relationship between IL-10 polymorphisms (rs1800896, rs1800871, and rs1800872) and BC risk. METHODS: Databases, including PubMed, Web of Knowledge, Embase, and Chinese National Knowledge Infrastructure, were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of associations. RESULTS: A total of 12 studies (4743 cancer cases and 5120 case-free controls) were eligible for meta-analysis. There were nine studies with 1851 cases and 1910 controls for rs1800896, six studies with 1034 cases and 1173 controls for rs1800871, and seven studies with 3637 cases and 3391 controls for rs1800872. Meta-analysis showed that rs1800896 and rs1800871 polymorphisms had no association with BC risk (for rs1800896: OR=1.060, 95% CI=0.785-1.432 in the dominant model, and OR=1.152, 95% CI=0.958-1.386 in the recessive model; for rs1800871: OR=0.952, 95% CI=0.859-1.056 in the dominant model, and OR=0.892, 95% CI=0.741-1.072 in the recessive model). However, rs1800872 polymorphism has association with BC risk based on the recessive model (OR=0.80, 95% CI=0.73-0.88). In the stratified analysis, when analyzed by the recessive model (CC vs. AA+AC), the ORs were 0.75 (95% CI=0.68-0.83) (p<0.00001) among Caucasians and 1.17 (95% CI=0.88-1.55) (p=0.27) among Asians. These results suggested that the CC homozygote has a 25% decreased risk of BC compared with those individuals with AA and AC genotypes in Caucasians. CONCLUSIONS: This meta-analysis showed that IL-10 rs1800896 and rs1800871 polymorphisms had no association with BC risk, while rs1800872 polymorphism had a decreased risk of BC in Caucasians.

Association between APE1 Single Nucleotide Polymorphism (rs1760944) and Cancer Risk: a Meta-Analysis Based on 6,419 Cancer Cases and 6,781 Case-free Controls.

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway. Epidemiological studies have suggested associations between APE1 rs1760944 polymorphism and cancer risk. This study was aimed to evaluate the relationship between APE1 rs1760944 polymorphism and cancer risk. We searched Pubmed, ISI Web of Knowledge, Embase, Chinese National Knowledge Infrastructure (CNKI) databases until September 2013 to identify eligible studies. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to estimate the strength of the associations. 12 studies from 11 articles on APE1 rs1760944 genotypes and cancer risk were identified, including a total of 6,419 cancer cases and 6,781 case-free controls. Overall, APE1 rs1760944 polymorphism was significantly associated with the decreased risk of cancer in any genetic models (G vs. T: OR = 0.86, 95% CI = 0.82-0.90; homozygote comparison: OR = 0.74, 95% CI = 0.67-0.82; heterozygote comparison: OR =0.88, 95%CI = 0.81-0.95; dominant model TG+GG vs. TT: OR = 0.82, 95% CI = 0.76-0.89; recessive model GG vs. TT+TG: OR = 0.81, 95%CI = 0.75-0.88). In the stratified analysis by populations, the effect was remain in studies of Asian population (homozygote comparison: OR = 0.71, 95%CI = 0.63-0.79; heterozygote comparison: OR = 0.86, 95 %CI = 0.79- 0.94; dominant model: OR = 0.80, 95% CI = 0.74 -0.87 and recessive model: OR = 0.78, 95%CI = 0.71-0.86). Moreover, a significantly decreased risk was found in lung cancer studies (homozygote comparison: OR = 0.68, 95% CI = 0.59-0.79; heterozygote comparison: OR = 0.86, 95%CI = 0.77- 0.98; dominant model: OR = 0.80, 95%CI = 0.72-0.90 and recessive model: OR= 0.77, 95% CI= 0.68-0.87). These findings support that APE1 rs1760944 polymorphism has a possible protective effect on cancer susceptibility particularly among Asians. Further studies based on different ethnicity and various cancer types are warranted to verify our findings.