Fujiao Duan

Genetic Polymorphisms in Long Noncoding RNA H19 Are Associated With Susceptibility to Breast Cancer in Chinese Population.

AbstractH19, a maternally expressed imprinted gene transcribing a long noncoding RNA, has previously been reported to be involved in tumorigenesis and cancer progression. However, the association between the H19 polymorphisms and breast cancer (BC) susceptibility has remained elusive. The aim of this study was to evaluate the associations between 2 H19 haplotype tagging SNPs (rs3741219 T>C, rs217727 C>T) and the risk of breast cancer.Our study comprised 464 BC patients and 467 cancer-free controls in China. rs3741219 and rs217727 were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created restriction site PCR (CRS-RFLP) assays, respectively. False-positive report probability (FPRP) was calculated to test the false-positive association.On performing univariate analysis, no significant association between H19 polymorphisms (rs3741219 and rs217727) and BC was observed. However, in further stratified analyses, CT+TT genotypes of rs217727 had a significantly lower risk of breast cancer among women with number of pregnancy >2 (OR = 0.79; 95% CI = 0.55–0.97). CT genotype of rs217727 was associated with ER positivity (OR = 2.19; 95 % CI = 1.07–4.45) and HER-2 positivity (OR = 1.34; 95 % CI = 1.05–2.12). It was proved that our results were less likely to be false positives according to false-positive report probability calculation.Our findings extend available data on the association of H19 polymorphisms and BC susceptibility. Further validation in large population or cohort studies is needed.

Systematic evaluation of cancer risk associated with rs2292832 in miR‑149 and rs895819 in miR‑27a: a comprehensive and updated meta‑analysis.

The aim of this study is to provide a precise quantification for the association between miR-149 T > C (rs2292832) and miR-27a A > G (rs895819) and the risk of cancer. We conducted a systematic literature review and evaluated the quality of included studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations. We identified 40 studies for pooled analyses. Overall, the results demonstrated that the rs2292832 polymorphism was subtly decrease the risk of breast cancer (CT + CC vs TT: OR = 0.83, 95% CI: 0.70–0.98, P = 0.03; CC vs CT + TT: OR = 0.80, 95% CI: 0.68–0.93, P = 0.00), and the rs895819 polymorphism wasassociated with significantly increased cancer risk in the Asian population (AG + GG vs AA: OR = 1.24, 95% CI: 1.03–1.50, P = 0.02) and in colorectal cancer subgroup (GG vs AA: OR = 1.45, 95% CI: 1.10–1.92, P = 0.00; AG + GG vs AA: OR = 1.35, 95% CI: 1.15–1.58, P = 0.00; GG vs AG + AA: OR = 1.36, 95% CI: 1.04–1.77, P = 0.02). In addition, a subtly decreased risk was observed in the Caucasian population and in breast cancer subgroup. In conclusion, the rs2292832 polymorphism was significantly associated with increased breast cancer risk, and the rs895819 polymorphism contributes to the susceptibility of colorectal and breast cancer.

Prognostic significance of low microRNA-218 expression in patients with different types of cancer: Evidence from published studies.

Background: Mounting evidence showed that microRNAs may be useful as prognostic biomarkers of cancer. Therefore, we summarize the predictive role of microRNA-218 (miR-218) for survival in patients with various cancers. Methods: We performed a systematic literature review and assessed the quality of included studies based on Meta-analysis of Observational Studies in Epidemiology group (MOOSE). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to assess the correlation between miR-218 expression and prognosis of different cancers. Results: We identified 10 studies for pooled analyses. For overall survival, a lower expression levels of miR-218 significantly predicted poorer survival, with the pooled HR of 2.61 (95% CI: 2.11–3.22, P < 0.001). For disease-free survival/progressive-free survival/recurrence-free survival (DFS/PFS/RFS), a lower expression level of miR-218 significantly predicted worse DFS/PFS/RFS in various carcinomas, with the pooled HR of 2.73 (95% CI: 2.08–3.58, P < 0.001). Similarly, subgroup analysis by detection method, ethnicity and cancer subtype analysis suggested that lower expression of miR-218 correlated with. Conclusion: Our data demonstrated that lower miR-218 expression is significantly associated with poorer overall survival (OS) and DFS/PFS/RFS and may be a novel prognostic biomarker in some cancer types.

Functional long non-coding RNAs associated with gastric cancer susceptibility and evaluation of the epidemiological efficacy in a central Chinese population

AIM To screen and validate the gastric cancer-associated long non-coding RNAs (lncRNAs) and their functional single nucleotide polymorphisms (SNPs). METHODS Based on case-control design, we select the differentially expressed lncRNAs by bioinformation tools and validate SNPs in lncRNAs genes in population. Attributable risk percentage (ARP) and population attributable risk percentage (PARP) were used to assess the effect of epidemiology. RESULTS Four lncRNAs with SNPs (lnc-EVX1-3:3 (rs1859168), lnc-MACC1-1:7 (rs3815254), lnc-AMFR-1:1 (rs4784659) and lnc-ZNF33B-2:1 (rs579501)) were selected to be validated in population. The unconditional multiple logistic regression based on the dominant (odds ratio, OR=0.64, 95%confidence interval, 95%CI: 0.47-0.86) and recessive genetic model (OR=1.77, 95%CI: 1.34-2.35) showed rs1859168 was significantly associated with lower risk of gastric cancer. The dominant (OR=0.42, 95%CI:0.31-0.57) and additive (OR=0.52, 95%CI:0.40-0.67) genetic model revealed that rs4784659 decreased the risk of gastric cancer. Similarly, the dominant (OR=0.72, 95%CI: 0.52-0.98) and additive (OR=0.73, 95%CI: 0.56-0.97) genetic model showed the individuals with rs579501 had reduced risk of gastric cancer. Whereas no statistical association between rs3815254 and gastric cancer. ARP and PARP for gastric cancer associated with rs1859168 in dominant model (56.25%, 33.05%), and in recessive model (43.50% and 29.37%). For rs4784659, ARP and PARP were 138.09% and 10.39% in dominant model, 92.31% and 8.76% in additive model. For rs579501, ARP and PARP were 38.89% and 4.03% in dominant model, 36.99% and 3.88% in additive model. CONCLUSION Our findings showed rs4784659, rs579501 and rs1859168 reduced the susceptibility of gastric cancer. From epidemiological perspective, the lncRNAs with SNPs attenuate the development of gastric cancer.

Esophageal Squamous Cell Carcinoma and Gastric Cardia Adenocarcinoma Shared Susceptibility Locus in C20orf54: Evidence from Published Studies

This study aimed to determine whether C20orf54 rs13042395 polymorphism modify the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA) in common population. We conducted a systematic literature review and evaluated the quality of included studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated to estimate the strengths of the associations. 9 articles (10 studies) were identified for synthesis analyses. Overall, the results indicated that the C20orf54 rs13042395 genotype was subtly decrease the risk of ESCC (T vs. C: OR = 0.95; 95%CI = 0.90–0.99; P = 0.02) and the rs13042395 polymorphism was associated with a decreased risk of GCA (T vs. C: OR = 0.95; 95%CI = 0.91–0.98; P < 0.01). The subsets were divided by smoking and drinking status, but none of the genetic comparisons reached statistical significance. Subgroup analysis was also stratified by body mass index (BMI), rs13042395 polymorphism was significantly associated with a subtly decreased cancer risk in under-weight group and normal group, but no association was observed in over-weight group. In conclusion, C20orf54 rs13042395 polymorphism was significantly associated with decreased ESCC and GCA risk especially for the subjects with under-weight or normal.

The significance of Exo1 K589E polymorphism on cancer susceptibility: evidence based on a meta-analysis.

The exonuclease1 (Exo1) gene is a key component of mismatch repair (MMR) by resecting the damaged strand, which is the only exonuclease involved in the human MMR system. The gene product is a member of the RAD2 nuclease family and functions in DNA replication, repair and recombination. However, whether Exo1 is required to activate MMR-dependent DNA damage response (DDR) remains unknown, the conclusions of the Exo1 polymorphisms on cancer susceptibility studies were not consistent. We carried out a meta-analysis of 7 case-control studies to clarify the association between the Exo1 K589E polymorphism and cancer risk. Overall,a significant association of the Exo1 K589E polymorphism with cancer risk in all genetic models (Lys vs Glu: OR = 1.51, 95%CI:1.39–1.99, P<0.01; Glu/Lys vs Glu/Glu: OR = 1.43, 95%CI:1.28–1.60, P<0.01; Lys/Lys vs Glu/Glu: OR = 2.45, 95%CI:1.90–3.17, P<0.01; Lys/Lys+Glu/Lys vs Glu/Glu: OR = 1.53, 95%CI:1.38–1.71, P<0.01; Glu/Glu vs Glu/Lys+Lys/Lys: OR =  2.27, 95%CI:1.79–2.89, P<0.01). In the stratified analysis by ethnicity, significantly increased risk was observed in Asian population (Lys vs Glu: OR = 1.53, 95%CI:1.39–1.69, P<0.01; Glu/Lys vs Glu/Glu: OR = 1.50, 95%CI:1.34–1.69, P<0.01; Lys/Lys vs Glu/Glu: OR = 2.48, 95%CI:1.84–3.34, P<0.01; Lys/Lys+Glu/Lys vs Glu/Glu: OR = 1.58, 95%CI:1.41–1.78, P<0.01; Glu/Glu vs Glu/Lys+Lys/Lys: OR = 2.18, 95%CI:1.62–2.93, P<0.01). Subgroup analysis based on smoking suggested Exo1 K589E polymorphism conferred significant risk among smokers (Lys/Lys+Glu/Lys vs Glu/Glu: OR = 2.16, 95%CI:1.77–2.63, P<0.01), but not in non-smokers (Lys/Lys+Glu/Lys vs Glu/Glu: OR = 0.89, 95%CI:0.64–1.24, P = 0.50). In conclusion, Exo1 K589E Lys allele may be used as a novel biomarker for cancer susceptibility, particularly in smokers.

The Effect of MUC1 rs4072037 Functional Polymorphism on Cancer Susceptibility: Evidence from Published Studies

Genome-wide association studies have identified a susceptibility variation MUC1 rs4072037 for gastric cancer in Chinese population. Subsequent case-control studies have reported this association in other populations. However, the results remain controversial and ambiguous. The aim of this study is to provide a precise quantification for the association between MUC1 rs4072037 variation and the risk of cancer. We performed pooled analysis of 10 case-control designed studies including 4,220 cases and 6,384 controls. Odds ratios (OR) and 95% confidence interval (95%CI) were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity and cancer types. All statistical analyses were performed by Manager 5.0 and Stata 12.0 software. Overall, the MUC1 rs4072037 polymorphism was associated with risk of cancer in all genetic models (G vs A: OR = 0.71, 95%CI: 0.63–0.80, p<0.01; GA vs AA: OR = 0.61, 95%CI:0.55–0.67, p<0.01; GG vs AA: OR = 0.58, 95%CI: 0.47–0.71, p<0.01; AG+AA vs GG: OR = 0.60, 95%CI: 0.55–0.60, p<0.01; GG vs AG+AA: OR = 0.70, 95%CI: 0.58–0.85, p<0.01). Further, subgroup analysis based on ethnicity suggested MUC1 rs4072037 polymorphism had a subtly reduced cancer risk among Asian population, and stratified analysis by cancer types showed significantly decreased risk of gastric cancer in all genetic models. In conclusion, MUC1 rs4072037 polymorphism may be used as potential biomarker for cancer susceptibility particularly for gastric cancer and for Asian population.

Evaluating the prognostic value of miR-148/152 family in cancers: based on a systemic review of observational studies

Background The prognostic significance of MicroRNA-148/152 (miR-148/152) family expression in various cancers has been investigated by many studies with inconsistent results. To address this issue, we performed a meta-analysis to clarify this relationship. Materials and Methods Eligible studies were recruited by a systematic literature search and assessed the quality of included studies based on Quality In Prognosis Studies (QUIPS) and Newcastle-Ottawa Scale (NOS). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and disease free survival/progressive free survival/recurrence free survival (DFS/PFS/RFS) were calculated to estimate the effects of miR-148/152 family expression on prognosis. Results A final total of 23 articles (26 studies) were considered in evidence synthesis. A significant association was observed between low miR-148a level and poor OS in patients (HR = 1.59, 95% CI: 1.14 – 2.20, P = 0.00), especially with digestive tract cancer (DTC) (HR = 1.29, 95% CI: 1.03–1.63, P = 0.03), and another significant association was observed between low miR-148b level and poor OS in patients (HR=2.09, 95% CI: 1.70–2.56, P = 0.00), especially with (hepatocellular carcinoma) HCC (HR = 1.97, 95% Cl: 1.52–2.56, P = 0.00) and non-small cell lung cancer (NSCLC) (HR = 2.29, 95% Cl: 1.64–3.18, P = 0.00). The significant correlation between miR-152 and DFS/RFS was found in our research (HR = 3.49, 95% Cl: 1.13–10.08, P = 0.03). Conclusions Our findings suggest that low miR-148/152 family expression is significantly associated with poor prognosis and may be a feasible prognostic biomarker in some cancers, especially in HCC and NSCLC.

Novel functional variants locus in PLCE1 and susceptibility to digestive tract cancer in the Chinese population: a meta-analysis.

Three large-scale genome-wide association studies (GWAS) have identified a shared susceptibility variation phospholipase C epsilon 1 (PLCE1) rs2274223 for esophageal squamous cell carcinoma (ESCC) and/or gastric cardia adenocarcinomas (GCA) in the Chinese population. However, the association between PLCE1 rs2274223 A>G and the risk of digestive tract cancer (DTC) has been inconsistent. We therefore carried out a meta-analysis of published case-control studies to derive a more precise estimation of the association between PLCE1 rs2274223 A>G and DTC risk. A comprehensive search was conducted to identify all eligible studies of PLCE1 rs2274223 polymorphism and DTC risk. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the strength of associations in fixed or random effect models. Heterogeneity and publication bias were also assessed. A total of 15 case-control studies were identified, including 29,805 cases and 32,225 controls. Overall, we found a statistically significant association between the PLCE1 rs2274223 polymorphism and DTC risk (G vs A: OR=1.29, 95% CI: 1.17-1.43; GA vs AA: OR=1.33, 95% CI: 1.18-1.51; GG vs AA: OR=1.71, 95% CI: 1.26-2.32; GG/GA vs AA: OR=1.33, 95% CI: 1.17-1.51), but the recessive model did not reach statistical significance (GG vs GA/AA: OR=0.94, 95% CI: 0.63-1.42). In the subgroup analysis by cancer types, we observed a significant risk for DTC in the ESCC and GCA subgroups. When stratified for source of controls, the results of the population-based subgroup analysis showed that the variant G allele might generally induce a significantly increased risk of DTC, except in hospital-based subgroups. In conclusion, PLCE1 rs2274223 polymorphism may be used as a potential biomarker for DTC susceptibility particularly for ESCC and GCA in the Chinese population.

Comprehensive Assessment of the Relationship Between MicroRNA-124 and the Prognostic Significance of Cancer

Background Numerous studies have demonstrated the presence of microRNA-124 abnormalities involving gene expression, methylation, and single nucleotide polymorphism (SNP) in multiple and diverse cancers, but the prognostic value of these abnormalities in cancer remains inconclusive. Objective The aim of this study is to determine the prognostic value of miR-124 in cancer. Methods We scrutinized the electronic databases and estimate the association between miR-124 expression, methylation and single nucleotide polymorphisms (SNPs), and prognosis in cancers. The pooled hazard ratios with 95% confidence intervals (CIs) for overall survival (OS), and disease-free survival/recurrence-free survival (RFS)/progression-free survival (PFS) were calculated to estimate the effects of miR-124 expression, methylation, and SNPs on cancer prognosis. The Quality in Prognosis Studies and Newcastle-Ottawa Scale were utilized to assess the quality of included studies. Results A total of 20 studies involving 3,574 participants were analyzed in evidence synthesis. Our findings showed that the low expression of miR-124 was significantly associated with poor OS (HR = 2.37, 95% CI: 1.91–2.94, P = 0.00; HR = 3.10, 95% CI: 2.04–4.70, P = 0.00) and PFS/RFS (HR = 2.21, 95% CI: 1.50–3.26, P = 0.00; HR = 2.12, 95% CI: 1.20–3.74, P = 0.00). The hyper-methylation of miR-124 was associated with poor OS (HR = 2.09, 95% CI: 1.48–2.95, P = 0.00) and PFS (HR = 3.70, 95% CI: 1.72–7.97, P = 0.00) (Table 3). The patients carrying with Allele C of miR-124 rs5315649 had a worse OS (HR = 1.50, 95% CI: 1.09–2.07, P = 0.00) and PFS (HR = 1.67, 95% CI: 1.20–2.33, P = 0.00) than the carriers with Allele G. Conclusion The low expression and hyper-methylation of miR-124 was strongly associated with poor prognosis, and genetic variations of miR-124 rs531564 affected prognosis in cancer patients.