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Background and Aim In our previous study, we demonstrated that four microRNAs (miRNAs) (miR-26a, miR-142-3p, miR-148a, and miR-195) that were downregulated in both plasma and tumor tissues were confirmed to be promising non-invasive diagnostic biomarkers for gastric cancer (GC). Methods We used the quantitative reverse transcription polymerase chain reaction to assess the expression levels of the four miRNAs from paraffin-embedded surgical specimens of GC patients. Kaplan–Meier curves and log-rank test were applied to predict the correlation between miRNAs and cumulative overall survival (OS) of patients with GC. Besides, we performed in vitro assays including cell proliferation, migration, invasion and colony formation, and apoptosis. Results The median of miRNA expression in paraffin-embedded tissues were used as the cutoff value to classify patients into high or low expression groups. Down-regulation of miR-26a and miR-148a was significantly associated with shorter OS of GC patients either in the test set (miR-26a: P = 0.009; miR-148a: P = 0.005) or the validation set (miR-26a: P = 0.011; miR-148a: P = 0.024). When two sets were combined, Cox regression analysis demonstrated that both of miR-26a and miR-148a were independent prognostic factors for predicting OS of patients with GC (miR-26a: HR = 0.76, 95% CI = 0.61–0.94; miR-148a: HR = 0.73, 95% CI = 0.58–0.91). Furthermore, elevated expression of miR-26 significantly suppressed cell proliferation, migration, invasion and colony formation, and induced apoptosis of MGC-803 cells compared with negative control groups (P

// Jiafei Lu 1, 2, * , Yongmei Yin 3, * , Mulong Du 1, 2, * , Gaoxiang Ma 1, 2 , Yuqiu Ge 1, 2 , Qiang Zhang 1, 2 , Haiyan Chu 1, 2 , Na Tong 1, 2 , Meilin Wang 1, 2 , Jinrong Qiu 3, 4 , Zhengdong Zhang 1, 2 1 Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China 2 Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China 3 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 4 Department of Biological-Therapy, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zhengdong Zhang, email: drzdzhang@gmail.com Jinrong Qiu, email: jrqiu@njmu.edu.cn Keywords: polymorphism, hOGG1 , gastric cancer, susceptibility Received: March 22, 2016 Accepted: August 24, 2016 Published: September 01, 2016 ABSTRACT Human 8-oxoguanine DNA glycosylase ( hOGG1 ) is known to play an important role in the prevention of carcinogenesis, including gastric cancer (GC). We performed a case-control study to investigate whether single nucleotide polymorphisms (SNPs) of hOGG1 are associated with GC risk in a Chinese population. Two potential functional tagSNPs (rs159153 and rs1052133) and a previously reported risk SNP (rs125701) were genotyped in 1,275 GC patients and 1,436 controls. We found that SNP rs125701 G > A was significantly associated with the increased GC risk [adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.05-1.79 in additive model]. Besides, the functional studies demonstrated that the minor A allele of rs125701 significantly reduced the transcriptional activity of hOGG1 promoter and enhanced the methylation level of CpG site of cg15357639. In conclusion, our results suggested that the SNP rs125701 in hOGG1 promoter was associated with the elevated GC risk, which could act as a new potential biomarker for GC susceptibility. Further functional verification of rs125701 in GC pathogenesis is warranted.

Genome-wide association studies (GWAS) of bladder cancer have identified a number of susceptibility loci in European populations but have yet to uncover the genetic determinants underlying bladder cancer incidence among other ethnicities. Therefore, we performed the first GWAS in a Chinese cohort comprising 3,406 cases of bladder cancer and 4,645 controls. We identified a new susceptibility locus for bladder cancer at 5q12.3, located in the intron of CWC27 (rs2042329), that was significantly associated with disease risk (OR = 1.40; P = 4.61 × 10−11). However, rs2042329 was not associated with bladder cancer risk in patients of European descent. The rs2042329 risk allele was also related to significantly increased expression levels of CWC27 mRNA and protein in bladder cancer tissues from Chinese patients. Additional functional analyses suggested that CWC27 played an oncogenic role in bladder cancer by inducing cell proliferation and suppressing apoptosis. In conclusion, the identification of a risk-associated locus at 5q12.3 provides new insights into the inherited susceptibility to bladder cancer in Chinese populations and may help to identify high-risk individuals. Cancer Res; 76(11); 3277–84. ©2016 AACR.

A polymorphism rs4938723 (T > C) within the promoter region of pri-miR-34b/c has been found to not only affect the expression of mature miR-34b/c but also contribute to the susceptibility to several cancer types. We designed a case-control study to evaluate the role of rs4938723 in childhood acute lymphoblastic leukemia (ALL). The rs4938723 CC genotype was significantly associated with reduced ALL risk (p = 0.003, ORadjusted = 0.51, 95% CI = 0.33-0.80 for CC vs. TT). Stratification analyses showed the differences were pronounced in older (> 6 years), male subjects, as well as in patients in low risk and T-ALL subtypes. The in vitro luciferase assays in Jurkat and K-562 cell lines showed that the transcription activity of miR-34b/c was increased when T allele transited to C allele (p

// Mulong Du 1, * , Weizhi Wang 2, * , Hua Jin 3, * , Qiaoyan Wang 1 , Yuqiu Ge 1 , Jiafei Lu 1 , Gaoxiang Ma 1 , Haiyan Chu 1, 4 , Na Tong 1, 4 , Haixia Zhu 3 , Meilin Wang 1, 4 , Fulin Qiang 3 , Zhengdong Zhang 1, 4 1 Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China 2 Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China 3 Core Laboratory, Nantong Tumor Hospital, Nantong, China 4 Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Zhengdong Zhang, e-mail: drzdzhang@gmail.com Keywords: long noncoding RNA, HOTAIR, genetic variants, gastric cancer Received: May 12, 2015 Accepted: August 24, 2015 Published: September 04, 2015 ABSTRACT The HOX transcript antisense intergenic RNA ( HOTAIR ), a well-known long noncoding RNA, is involved in pathogenesis and progress of multiple tumors. Its ectopic expression and biological functions have been observed in gastric cancer. In this study, we conducted a two-stage case-control study to evaluate whether genetic variations of HOTAIR were associated with gastric cancer risk. We identified that a single nucleotide polymorphism (SNP) rs4759314 was significantly associated with the increased gastric cancer risk with an odds ratio (OR) of 1.39 [95% confidence interval (CI) = 1.13–1.71, P = 0.002] in the combined sets. Further functional experiments revealed the allele-specific effects on HOTAIR and HOXC11 expressions in gastric cancer tissues, of which HOTAIR and HOXC11 expressions of individuals carrying with AG genotype were much higher than those with AA genotype; similarly, the effects occurred in intronic promoter activities, of which the promoter activity of G allele was more pronounced than that of A allele. Interestingly, we identified a novel potential oncogene HOXC11 in gastric cancer pathogenesis with differential expression in gastric cancer tissues by association analysis with candidate gene strategy. These results suggest that SNP rs4759314 of HOTAIR acts as a potential biomarker for predicting gastric cancer, and the role of HOXC11 in gastric cancer etiology is warranted to further investigation.

Background MicroRNAs (miRNAs) have been demonstrated playing important roles in the procession of prostate cancer cells transformation from androgen-dependence to androgen-independence. Methods We conducted the miRNA microarray and realtime PCR analyses in both androgen-dependent (ADPC) and androgen-independent prostate cancer (AIPC) tissues. We also explored the role of hsa-miR-146a-5p (miR-146a) in MSKCC prostate cancer clinical database. Moreover, the impact of miR-146a on prostate cancer cells apoptosis were detected by Hoechst staining and fluorescence-activated cell sorter (FACS). Its target is predicted by DIANA LAB online database and the result was assumed by western blotting and luciferase assay. Results We demonstrated that miR-146a was down-regulated in AIPC tissues and cell lines compared to that in the ADPC tissues. In MSKCC data re-analyses, we found that miR-146a was underexpressed in metastatic prostate cancer tissues and those with Gleason score >8, moreover, low level of miR-146a represented a high biochemical relapse rate after radical prostatectomy. In the functional analyses, we transfected miR-146a mimics into CPRC cell lines and found miR-146a induced cells apoptosis. In mechanic analyses, we found that miR-146a inhibited the basal level of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) expression by targeting its 3'UTR and an inverse correlation of expression between miR-146a and ROCK1 was observed. Moreover, caspase 3 activity was stimulated by miR-146a overexpression. Conclusion miR-146a has a critical role in the process of AIPC prostate cancer cells apoptosis through regulation of ROCK/Caspase 3 pathway. Targeting this pathway may be a promising therapeutic strategy for future personalized anti-cancer treatment. Prostate 75:1896–1903, 2015. © 2015 Wiley Periodicals, Inc.

Background and Aim Single nucleotide polymorphisms (SNPs) located in long noncoding RNA CASC8 gene may influence the process of splicing and stability of messenger RNA conformation, resulting in the modification of its interacting partners. Genome-wide association studies have identified the SNP rs10505477 and SNP rs1562430 in CASC8 were associated with risk of the colorectal cancer (CRC) and breast cancer, respectively. Methods In the present study, we genotyped the 940 surgically resected gastric cancer patients to explore the association between these two SNPs (e.g. rs10505477 and rs1562430) and survival of gastric cancer in a Chinese population. Results We found that the patients carrying rs10505477 GG genotype survived for a longer time than those with the GA and AA genotypes (log-rank P = 0.030). The similar result was also found in the dominant model (GA/AA vs GG, HR = 1.32, 95% CI = 1.08–1.63, log-rank P = 0.008). This risk effect was more pronounced among patients with tumor size ≤ 5 cm, diffuse-type gastric cancer, lymph node metastasis, no distant metastasis, and TNM stage III and IV. Furthermore, the area under the curve at five years was dramatically increased from 0.619 to 0.624 after adding the rs10505477 risk score to the traditional clinical risk score (TNM stage and lymph node metastasis). However, there was no association be found between the rs1562430 and the survival of gastric cancer. Conclusion These findings suggested the SNP rs10505477 may contribute to the survival of gastric cancer and be a potential prognostic biomarker of gastric cancer.

This study investigated the gene transcription and activities of iodothyronine deiodinases in the hepatic cell line of grass carp (Ctenopharyngodon idella) exposed in vitro to 1, 10, 100, and 1000 μg /L microcystin-LR (MC-LR) for either 24 or 48 h. The cell viabilities were not significantly affected by MC-LR exposure. The mRNA expressions of type I iodothyronine deiodinase (ID1) and type Ⅱ iodothyronine deiodinase (ID2) reduced after the exposure to MC-LR. However, MC-LR exposure led to the increase in the mRNA expression of type Ⅲ iodothyronine deiodinase (ID3). Moreover, significant ID1 and ID2 activities decline were also observed in the hepatic cell line of grass carp exposed to MC-LR, and the activity of ID3 increased significantly in the MC-LR treated groups. The results suggested that MC-LR could alter the gene transcription or activities of IDs in the hepatic cell line of grass carp.

Single nucleotide polymorphisms (SNPs) in the 3′-untranslated regions (UTRs) targeted by putative mircoRNAs (miRNAs) could influence the susceptibility of cancer. Recently, miR-29c has been reported to be down-regulated in gastric cancer (GC) and serve as a tumor suppressor that regulated tumor progression. The present study was aimed at investigating whether the miR-29c binding site SNPs within the 3′-UTRs of target genes affected the gastric cancer risk. Using bioinformatics tools, we chose three SNPs (IGHMBP2 rs3750980, LAMTOR3 rs11944405 and WWOX rs2288035) located in miR-29c binding sites. We genotyped these three SNPs to assess their associations with GC risk in a case-control study comprising 753 GC cases and 950 controls. Among these three SNPs, we found a significantly decreased risk of GC associated with the LAMTOR3 rs11944405 T > C polymorphism [TC vs. TT, adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63–0.99; TC/CC vs. TT, adjusted OR = 0.81, 95% CI = 0.65–1.00]. The significant association was also presented in the subgroup analysis by age (≤ 65), sex (female), depth of invasion (T3/T4), lymph node metastasis (N1-3), distant metastasis (M0) and TNM stage (III/IV). However, no significant association was detected for IGHMBP2 rs3750980 and WWOX rs2288035. Our results suggested that the LAMTOR3 rs11944405 polymorphism may be a potential biomarker for genetic susceptibility to GC.

Current procedures for diagnosis and biomarker examination of colorectal cancer (CRC) are invasive and unpleasant. There is a great need to identify sensitive and specific biomarkers for early diagnosis of CRC. Circulating microRNAs (miRNAs) are promising molecular markers for CRC prediction. We performed a comprehensive meta-analysis to integrate an evaluation index for diagnostic accuracy of circulating miRNAs in diagnosing CRC patients. Furthermore, we conducted an independent validation set of 49 CRC patients and 49 healthy controls. In our meta-analysis, we found that miR-21 yielded a pooled area under ROC curve (AUC) of 0.867 (sensitivity: 76%, specificity: 82%) in discriminating CRC from controls, and miR-92a yielded a summary AUC of 0.803 (sensitivity: 77%, specificity: 68%); miR-21 had a higher diagnostic efficiency than miR-92a. In the further validation, plasma miR-21 levels in CRC patients were significantly higher than levels observed in healthy subjects. A ROC curve analysis showed a consistent result. However, this phenotype was not present in miR-92a. Moreover, the expression trend of miR-21 in plasma samples was in line with that of tissue samples, along with the cellular level. Current evidences suggest that plasma miR-21 could be a reliable and non-invasive biomarker for CRC diagnosis. Studies with larger cohorts that include the diagnostic value of plasma miR-21 for CRC are warranted.

Background/Aims: FOXO3a is an essential tumor suppressor that regulates the mechanisms of tumorigenesis and leukemogenesis. FOXO3a polymorphisms have not been reported previously associated with an increased risk for childhood acute lymphoblastic leukemia (ALL). In this study, the rs4946936 polymorphism located in the 3'UTR of FOXO3a was selected to evaluate its relationship with a risk for ALL in Chinese children. Methods: Questionnaires, SNaPshot genotyping, real-time PCR, cell transfection and dual luciferase reporter assays were used in this study. Results: Parental alcohol consumption and whether the child’s house had been painted had significantly different distributions among the cases and controls. In addition, the C to T mutation was significantly associated with the risk for ALL. We determined that FOXO3a expression levels in patients with the CT or TT genotype were significantly higher than those of patients with the CC genotype. The T allele significantly increased the expression levels in luciferase assays and affected the binding affinity of miR-223 to the FOXO3a 3'UTR. Conclusion: Rs4946936 in FOXO3a was highly associated with an increased risk of childhood ALL in a Chinese population.

Acute lymphoblastic leukemia (ALL) is a major cause of mortality and morbidity in childhood, and the causes of ALL are not completely understood. microRNAs (miRNAs) regulate various biological processes including organ development, cell growth regulation, cell differentiation, apoptosis, and tumorigenesis. We performed a case–control study with 570 childhood ALL cases and 673 cancer-free controls to investigate the association between hsa-miR-196a2 rs11614913 T > C polymorphism and ALL risk. The bioinformatics was used to estimate the potential target of hsa-miR-196a2. In the present study, the hsa-miR-196a2 variant TC heterozygote, and CC/TC genotypes were found to be associated with a significantly increased childhood ALL risk, compared with the TT wild-type homozygote (adjusted OR = 1.50, 95% CI = 1.15–1.95 for TC and OR = 1.40, 95% CI = 1.09–1.79 for CC/TC). Further, the difference was pronounced in younger (≤6) subjects or parental non-drinker. The significance of the increased risk is more obvious than the higher treatment branch. Additionally, we found that the rs11614913 TC genotype can increase B-phenotype ALL risk (OR = 1.37, 95% CI = 1.07–1.76). Finally, combination of three bioinformatics approaches revealed that HOXC8 may be the target gene of hsa-miR-196a2. Taken together, our finding suggested that hsa-miR-196a2 rs11614913 T > C may increase the risk of childhood ALL. Large studies with the function of hsa-miR-196a2 are needed in the further study.

It is well known that the tea extracts, mainly polyphenols as chemo-preventive elements, could act as cancer progression blockers. Although the association between tea consumption and colorectal cancer risk has been widely investigated, the results still remain inconsistent. We conducted a dose-response meta-analysis to evaluate their relationships by enrolling qualified 29 literatures. The summary odds ratio (OR) of colorectal cancer for the highest vs. lowest tea consumption was 0.93 with 0.87-1.00 of 95% confidence intervals (CIs) among all studies with modest heterogeneity (P = 0.001, I2 = 43.4%). Stratified analysis revealed that tea, especially green tea, had a protective effect among female and rectal cancer patients. Particularly, the dose-response analysis showed that there was a significant inverse association between an increment of 1 cup/day of tea consumption and colorectal cancer risk in the subgroup of the green tea drinking (OR = 0.98, 95% CI = 0.96-1.01, Pnonlinear = 0.003) and female (OR = 0.68, 95% CI = 0.56-0.81, Pnonlinear < 0.001). Our findings indicate that tea consumption has an inverse impact on colorectal cancer risk, which may have significant public health implications in the prevention of colorectal cancer and further similar researches.

// Haiyan Chu 1, 2, 3 , Yaoyao Chen 1 , Qinbo Yuan 4, 5 , Qiuhan Hua 1 , Xu Zhang 1 , Meilin Wang 1, 2 , Na Tong 1 , Wei Zhang 5 , Jinfei Chen 3 and Zhengdong Zhang 1, 2 1 Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China 2 Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China 3 Department of Oncology, The Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing, China 4 Department of Urology, Huaiyin Hospital of Huai’an City, Huai’an, China 5 Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China Correspondence to: Zhengdong Zhang, email: drzdzhang@gmail.com Keywords: lncRNA, polymorphism, meta-analysis, cancer, epidemiology Received: August 29, 2016 Accepted: December 27, 2016 Published: January 31, 2017 ABSTRACT Long non-coding RNAs (LncRNAs) have been widely studied and aberrant expression of lncRNAs are involved in diverse cancers. Genetic variation in lncRNAs can influence the lncRNAs expression and function. At present, there are many studies to investigate the association between lncRNAs polymorphisms and cancer susceptibility. However, it has no systematic study to evaluate the association. We performed a meta-analysis to summarize the results of common lncRNAs ( HOTAIR , PRNCR1 , POLR2E and H19 ) polymorphisms on cancer risk, by using the random-effect model to obtain the odds ratio (ORs) and 95% confidence interval (95%CI). We also applied the meta-regression and publication bias analysis to seek the source of heterogeneity and evaluate the stability of results, respectively. The summary results indicated that HOTAIR rs920778 increased the cancer risk in recessive model (OR = 1.61, 95% CI = 1.08-2.41, P heterogeneity

Human oxoguanine glycosylase 1 (hOGG1) is a DNA repair enzyme, which plays important roles in the base excision repair (BER) pathway. Several studies reported a common polymorphism Ser326Cys (rs1052133) in hOGG1, which conferred the susceptibility of bladder cancer. We hypothesized that the polymorphism is associated with risk of bladder cancer in a Chinese population. In a case‐control study of 1050 histologically confirmed bladder cancer patients and 1404 age and sex matched healthy controls, we genotyped the hOGG1 Ser326Cys polymorphism using TaqMan technology and assessed its association with bladder cancer risk. We found that the hOGG1 Ser/Cys + Ser/Ser genotypes were associated with a significantly increased risk of bladder cancer (adjusted odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01–1.41), compared with the Cys/Cys genotype. Furthermore, the increased risk was more pronounced among subjects over age 65 years (OR = 1.31, 95% CI = 1.04–1.66), male subjects (OR = 1.21, 95% CI = 1.00–1.47), ever smokers (OR = 1.29, 95% CI = 1.00–1.68) and heavy smokers (>20 pack‐years) (OR = 1.45, 95% CI = 1.03–2.04). No significant association was observed in the stratification of tumor grade and tumor stage for bladder cancer. In conclusion, our results suggest that hOGG1 Ser326Cys polymorphism may contribute to the susceptibility to bladder cancer in a Chinese population. (Cancer Sci 2012; 103: 1215–1220)

Telomeres are involved in maintaining chromosomal stability, cellular immortality and tumorigenesis. A recent genome-wide association study has identified an association between telomere length and two common variants (rs12696304 and rs16847897) at 3q26 that includes TERC. We hypothesized that the two variants and relative telomere length (RTL) would be predictors of the risk of childhood acute lymphoblastic leukemia (ALL). A case-control study of 570 cases and 673 cancer-free controls among Chinese children was performed. We found that there was a protective relationship between the second and third quartiles of RTL and risk of ALL [adjusted odds ratio (OR) with 95% confidence interval (95% CI) by quartile: 0.65 (0.47-0.91), 0.56 (0.40-0.79)], compared with the first quartile (shortest) RTL. Moreover, rs16847897 CG genotype increased the risk of childhood ALL by 29% compared with the CC genotype. Our findings indicate that extreme telomere length may be a potential predictor for future risk of ALL, and TERC rs16847897 may contribute to the development of childhood ALL.

Single-nucleotide polymorphisms in microRNAs (miRNAs) may alter miRNA expression levels or processing and, thus, may contribute to cancer development. We hypothesized that miRNA-196a2 polymorphism is associated with risk of colorectal cancer (CRC). In a case-control study of 573 patients with CRC and 588 cancer-free controls frequency matched by age and sex, we genotyped the functional polymorphism rs11614913 (T>C) and assessed its association with the risk of CRC in a Chinese population. We found that the CT/CC genotypes were associated with a significantly increased risk of CRC (odds ratio [OR]=1.44, 95% confidence interval [CI]=1.10-1.88), compared with the TT genotype. Further, the polymorphism was significantly associated with the risk of patients with advanced stage tumor (Dukes C and D) (OR=1.65, 95% CI=1.11-2.46). Our results suggest that the functional polymorphism rs11614913 in miRNA-196a2 is involved in the etiology of CRC and, thus, may be a marker for genetic susceptibility to CRC.

BACKGROUND Castration-resistant prostate cancer (CRPC) is a leading cause of cancer-related deaths in elder men. This disease has limited therapeutic options and poor prognosis as the underlying molecular mechanisms are not clearly understood. Given the emerging roles of microRNA (miRNA) as a key regulator, we postulated that miRNA may play a significant role in CRPC formation. METHODS miR-146a levels in 15 androgen-dependent prostate cancer (ADPC) tissues and 5 CRPC tissues were measured by qRT-PCR. Effects of miR-146a in cell proliferation and migration in vitro and in vivo were evaluated by MTT assay, colony formation assay, transwell migratory assay, and tumor formation assay, respectively. RESULTS we found that miR-146a expression was significantly decreased in CRPC tissues compared to ADPC tissues. Functional analyses showed that ectopic overexpression of miR-146a in androgen-independent cell lines not only inhibited cell growth, colony formation, and migration in vitro, but also reduced tumorigenicity and angiogenesis in vivo. Mechanistic studies revealed that miR-146a repressed the expression of EGFR through binding to its 3′-untranslated region. Also, miR-146a inhibited the expression of MMP2, one of the most important genes in tumor progression. Moreover, downregulation of p-ERK expression significantly abrogated miR-146a-induced prostate cancer cell proliferation. CONCLUSIONS Our findings suggest that ubiquitous loss of miR-146a is a critical mechanism for overexpression of EGFR in CRPC, which is crucial to better understanding the pathogenesis of CRPC. Prostate 72:1171–1178, 2012. © 2011 Wiley Periodicals, Inc.

Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation and nucleotide synthesis. Accumulated evidence has demonstrated that C677T and A1298C polymorphisms of the MTHFR gene are associated with acute lymphoblastic leukemia (ALL) risk, but the results have been inconclusive. To determine a more precise estimation, we performed a meta-analysis of 28 studies with 4240 cases and 9289 controls. We found that the 677TT genotype showed a reduced risk of ALL compared with the 677CC genotype in the overall population (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.61-0.92). The reduced risk was pronounced only among the Caucasian population (OR 0.68, 95% CI 0.51-0.90), not the Asian (OR 0.89, 95% CI 0.75-1.05). For the MTHFR A1298C polymorphism, no significant association with ALL susceptibility was observed in the pooled analyses. However, significantly increased ALL risk was found in childhood in the comparison of 1298CA versus AA genotype. This study provides evidence that MTHFR polymorphisms may play an important role in the development of ALL.

OBJECTIVES To identify predictors for repeat biopsies in Chinese men with increasing prostate-specific antigen (PSA) levels or other risk factors for prostate cancer. METHODS The study included 129 patients who underwent transrectal sonography-guided repeat biopsies. Potential predictors, including age, body mass index, symptoms, digital rectal examination (DRE), total PSA, free PSA, free/total PSA ratio, prostate volume, PSA density, PSA velocity, PSA doubling time, and volume/biopsy ratio, were subjected to univariate analysis. Multivariate stepwise logistic regression was performed to identify major independent predictors for repeat biopsies, and a scoring system for predicting cancer was devised. A receiver operating characteristic (ROC) curve was constructed to test the sensitivity and specificity of the scoring system. RESULTS Thirty-four patients (26.36%) had cancer. On univariate analysis, the DRE (P = .002), total PSA (P = .020), free/total PSA ratio (P < .001), prostate volume (P < .001), PSA density (P = .003), and volume/biopsy ratio (P < .001) were significant predictors of cancer. On multivariate analysis, the DRE, total PSA, free/total PSA ratio, and volume/biopsy ratio were independently significant predictors, with odds ratios and 95% confidence intervals of 4.61 (1.62-13.07), 1.02 (1.00-1.04), 0.87 (0.78-0.96), and 0.56 (0.43-0.79). Using ROC analysis, we determined a cutoff value of 2.5 for the scores, at which the sensitivity and specificity of the scoring system for predicting positive repeat biopsy results were 76.50% and 74.70%, with an area under the curve of 0.816 (P < .001). Patients with scores of 3 to 5 had higher cancer detection rates than those with scores of 0 to 2 (52.00% versus 10.13%; P < .001). CONCLUSIONS Key predictors may exist to help formulate a scoring system to identify Chinese men who need repeat prostate biopsies. More studies are required to learn its applicability to broader populations.

Interleukin-6 (IL-6) is a multifunctional cytokine involved in different physiologic and pathophysiologic processes and plays important roles in the etiology of cancer. The -174G>C polymorphism of the IL-6 gene influences IL-6 transcription and has been implicated in cancer risk. However, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 29,377 cancer cases and 37,739 controls from 50 published case-control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between -174G>C polymorphism and cancer risk. Overall meta-analysis indicated that no association was found between -174G>C genotypes and cancer risk. However, the positive association was found in bladder cancer (OR=4.33, 95% CI: 1.93-9.71 for CC vs. GC, OR=2.81, 95% CI: 1.39-5.68 for CC vs. GG, and OR=2.19, 95% CI: 1.32-3.64 for CC vs. GG/GC), and among Asians (OR=2.08, 95% CI: 1.07-4.06 for CC vs. GG, and OR=2.20, 95% CI: 1.02-4.74 for CC vs. GG/GC) and Africans (OR=1.61, 95% CI: 1.07-2.42 for GC vs. GG). This meta-analysis showed the evidence that the -174G>C of the IL-6 gene was a low-penetrance susceptibility gene for bladder cancer. Further larger, preferably prospective studies are needed to confirm this relationship.

Introduction: Alterations in P53 and Murine Double Minute 2 (MDM2) genes appear to be important in the development of many human tumors. We investigated the potential prognostic roles of p53 codon 72 and MDM2 309 and 1797 polymorphisms in prostate cancer after radical prostatectomy. Patients and Methods: Fifty southern Chinese with prostate cancer undergoing radical prostatectomy were included in this study. All polymorphisms were detected by PCR-RFLP. Their prognosis on biochemical recurrence was assessed using Kaplan-Meier analysis and Cox regression model. Results:p53 codon 72 GG genotype was associated with increased biochemical recurrence compared with CG+CC genotypes and poorer PSA-free survival. It was also noted that GG genotype was an independent risk factor for biochemical recurrence after radical prostatectomy on multivariate analysis. No statistical difference was observed in MDM2 polymorphisms and prostate cancer prognosis. Conclusion: Our data revealed that p53 codon 72 GG genotype carriers more frequently show biochemical recurrence than CG+CC genotypes carriers.

Vascular endothelial growth factor (VEGF) is a major driver of physiological and pathological angiogenesis and plays important roles in the etiology and metastasis of cancers. The −460C>T polymorphism in VEGF gene region has been implicated in cancer risk and related to VEGF expression. However, published data remain conflicting. To derive a more precise estimation, a meta-analysis of 5,863 cases and 5,276 controls from 14 published case–control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. VEGF −460T represented a risk factor for cancers in Asians (OR = 1.69, 95% CI: 1.09–2.62) but not in Europeans (OR = 0.92, 95% CI: 0.78–1.08). Our meta-analysis showed the evidence that VEGF −460T was associated with increased cancer risk in Asians. Further prospective researches with larger numbers of worldwide participants are expected to validate this result.

P53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies revealing conflicting results on the role of p53 codon 72 polymorphism (G>C) on breast cancer risk led us to perform a meta-analysis to investigate this relationship. Thirty-nine published studies, including 26,041 breast cancer cases and 29,679 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results suggested that the variant genotypes were associated with a significantly reduced breast cancer risk (GC vs. GG: OR = 0.91, 95% CI: 0.83-1.00; CC/GC vs. GG: OR = 0.90, 95% CI: 0.82-0.99). In the stratified analyses, significantly decreased risks were also found among European populations (GC vs. GG: OR = 0.89, 95% CI: 0.80-0.99; CC/GC vs. GG: OR = 0.88, 95% CI: 0.80-0.98) and studies with population-based controls (GC vs. GG: OR = 0.88, 95% CI: 0.78-0.98; CC/GC vs. GG: OR = 0.87, 95% CI: 0.78-0.97). The results suggested that p53 codon 72 polymorphism may contribute to susceptibility to breast cancer, especially in Europeans. Additional well-designed large studies were required to validate this association in different populations.

Objective p53 is a tumor suppressor gene and is involved in the etiology of ovarian cancer. Studies investigating the associations between the p53 codon 72 polymorphism and ovarian cancer risk showed conflicting results. We performed this meta-analysis from eligible studies to evaluate this purported relationship. Methods This meta-analysis was performed from 9 case-control studies, including 825 ovarian cases and 1073 controls. T he fixed and random effect models were used to estimate the odds ratios(ORs) for various contrasts of this polymorphism. Results The combined results based on all studies showed that a significantly decreased risk was associated with the variant Pro/Pro genotype, compared with Arg/Pro+Arg/Arg genotypes(OR, 0.70; 95%CI, 0.51∼0.95). When stratifying the studies by ethnicity, we found that individuals with the variant genotype Pro/Pro had a significantly decreased risk of ovarian cancer compared with Arg/Arg genotype(OR, 0.43; 95%CI, 0.20∼0.89) and Arg/Pro+Arg/Arg genotypes(OR, 0.61; 95%CI, 0.37∼0.99) among Africans. Conclusion This meta-analysis suggests that the p53 codon 72 polymorphism may contribute to genetic susceptibility to ovarian cancer. More studies based on larger sample size should be performed to confirm the findings.

Evidence has shown that miR-146a is involved in carcinogenesis and a common G/C variant (rs2910164) in the pre-miR-146a gene has been found to be associated with various cancers. We investigated the potential prognostic role of miR-146a polymorphism in prostate cancer after radical prostatectomy. Seventy-two southern Chinese with prostate cancer undergoing radical prostatectomy were included in this study. miR-146a polymorphism was analyzed by PCR-RFLP. Its prognostic role in biochemical recurrence was assessed using Kaplan-Meier analysis and Cox regression model. We did not find a significant association between miR-146a polymorphism and prostrate-specific antigen failure in the Chinese population [HR (95%CI): 0.83 (0.30-2.32) for CC vs GG/GC]. However, high Gleason score (over 8) was associated with increased biochemical recurrence and poorer PSA-free survival. This study was limited by the length of follow-up. Future studies with longer follow-up would allow evaluation of more direct metrics, such as disease-specific survival, metastasis-free survival, and overall survival.

This study was conducted to compare the clinical curative effect and acute radiation lung reactions between CyberKnife (CK) and three-dimensional conformal radiotherapy (3DCRT) treatment for inoperable stage I peripheral non-small-cell lung cancer (NSCLC). We retrospectively analyzed 68 patients with inoperable stage I peripheral NSCLC between 2012 and 2013 in our institution. The CK patients were treated with 42–60 Gy in three fractions, while the 3DCRT patients were treated with a total of 60 Gy, at 2 Gy per fraction. The patients were followed up and the clinical outcome was evaluated according to the Response Evaluation Criteria in Solid Tumours. We assessed the presence of acute radiation pneumonitis and pulmonary function status by thoracic scan and pulmonary function tests following CK and 3DCRT treatment. The binary univariate logistic regression analysis demonstrated that treatment method and forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) prior to treatment (pre-FEV1/FVC) were the main factors affecting the risk of radiation pneumonitis. The analysis of these factors through multivariate logistic regression method demonstrated that treatment method for grade 1 and 2 [odds ratio (OR)= 7.866 and 11.334, respectively) and pre-FEV1/FVC for grade 1, 2 and 3 (OR = 5.062, 11.498 and 15.042, respectively) were significant factors affecting the risk of radiation pneumonitis (P

Long non-coding RNA HOX transcript antisenseRNA (HOTAIR) has been widely identified to participate in tumour pathogenesis, acting as a promoter in colorectal cancer carcinogenesis. However, the association between genetic variants in HOTAIR and cancer risk has not yet been reported. In the present study, we performed a two-stage case-control study to investigate the association between HOTAIR tagSNPs and the risk of colorectal cancer. We found that individuals with rs7958904 CC genotype had a significantly decreased risk of colorectal cancer in both Stage 1 and 2, compared with those carrying GG genotype [odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.51-0.97 in Stage 1; OR = 0.58, 95% CI = 0.37-0.91 in Stage 2; OR = 0.67, 95% CI = 0.51-0.87 in combined stage]. The subsequently stratified analyses showed that the protective effect of rs7958904 was more pronounced in several subgroups. In summary, our study showed that genetic variants in HOTAIR were associated with risk of colorectal cancer and rs7958904 may act as a potential biomarker for predicting the risk of colorectal cancer.

Recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese population has identified two novel single nucleotide polymorphisms (SNPs) rs11066280 and rs2074356 on C12orf51 gene. We hypothesized that SNPs rs11066280 and rs2074356 could influence gastric cancer survival outcomes. We genotyped the SNPs rs11066280 and rs2074356 in 940 patients with surgically resected gastric cancer. Analyses of genotype association with survival outcomes were assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. There was no significant association between rs11066280 and survival of gastric cancer. However, in the stratification analysis of histology, we found that the rs11066280 TA/AA genotypes were associated with a poor survival of intestinal-type gastric cancer (log-rank P = 0.041, hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.02–1.93), Moreover, this hazardous effect was more prominent among patients with tumor size > 5 cm, no distant metastasis, chemotherapy and drinking. No significant association was observed between rs2074356 and the survival of gastric cancer. C12orf5 rs11066280 could be useful marker of survival assessment and individualized clinical therapy for gastric cancer, particularly among the intestinal-type gastric cancer.

Although some studies have assessed the prognostic value of HOTAIR in patients with digestive system tumors, the relationship between the HOTAIR and outcome of digestive system tumors remains unknown. The PubMed was searched to identify the eligible studies. Here, we performed a meta-analysis with 11 studies, including a total of 903 cases. Pooled hazard ratios (HRs) and 95 % confidence interval (CI) of HOTAIR for cancer survival were calculated. We found that the pooled HR elevated HOTAIR expression in tumor tissues was 2.36 (95 % CI 1.88–2.97) compared with patients with low HOTAIR expression. Moreover, subgroup analysis revealed that HOTAIR overexpression was also markedly associated with short survival for esophageal squamous cell carcinoma (HR 2.19, 95 % CI 1.62–2.94) and gastric cancer (HR 1.66, 95 % CI 1.02–2.68). In addition, up-regulated HOTAIR was significantly related to survival of digestive system cancer among the studies with more follow-up time (follow time ≥ 5 years) (HR 2.51, 95 % CI 1.99–3.17). When stratified by HR resource and number of patients, the result indicated consistent results with the overall analysis. Subgroup analysis on ethnicities did not change the prognostic influence of elevated HOTAIR expression. Additionally, we conducted an independent validation cohort including 71 gastric cancer cases, in which patients with up-regulated HOTAIR expression had an unfavorable outcome with HR of 2.10 (95 % CI 1.10–4.03). The results suggest that aberrant HOTAIR expression may serve as a candidate positive marker to predict the prognosis of patients with carcinoma of digestive system.

The human murine double minute 2 (MDM2) is known as an oncoprotein through inhibiting P53 transcriptional activity and mediating P53 ubiquitination. Therefore, the amplification of MDM2 may attenuate the P53 pathway and promote tumorigenesis. The SNP309 T>G polymorphism (rs2279744), which is located in the intronic promoter of MDM2 gene, was reported to contribute to the increased level of MDM2 protein. In this hospital-based case-control study, which consisted of 573 cases and 588 controls, we evaluated the association between MDM2 SNP309 and the risk of colorectal cancer (CRC) in a Chinese population by using the TaqMan method to genotype the polymorphism. We found that the MDM2 SNP309 polymorphism was significantly associated with CRC risk. In addition, in our meta-analysis, we found a significant association between MDM2 SNP309 and CRC risk among Asians, which was consistent with our results. In conclusion, we demonstrated that the MDM2 SNP309 polymorphism increased the susceptibility of CRC in Asian populations.

Problem-based learning (PBL) is defined as a student-centered pedagogy which can provide learners more opportunities for application of knowledge acquired from basic science to the working situations than traditional lecture-based learning (LBL) method. In China, PBL is increasingly popular among preventive medicine educators, and multiple studies have investigated the effectiveness of PBL pedagogy in preventive medicine education. A pooled analysis based on 15 studies was performed to obtain an overall estimate of the effectiveness of PBL on learning outcomes of preventive medicine. Overall, PBL was associated with a significant increase in students' theoretical examination scores (SMD = 0.62, 95% CI = 0.41-0.83) than LBL. For the attitude- and skill-based outcomes, the pooled PBL effects were also significant among learning attitude (OR = 3.62, 95% CI = 2.40-5.16), problem solved skill (OR = 4.80, 95% CI = 2.01-11.46), self-directed learning skill (OR = 5.81, 95% CI = 3.11-10.85), and collaborative skill (OR = 4.21, 95% CI = 0.96-18.45). Sensitivity analysis showed that the exclusion of a single study did not influence the estimation. Our results suggest that PBL of preventive medicine education in China appears to be more effective than LBL in improving knowledge, attitude and skills.

MicroRNAs (miRNAs) are a class of short non-coding, single-stranded RNAs, which perform posttranscriptional regulatory functions as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) genes are currently being identified for contributing to cancer risk, prognosis and survival. We investigated whether genetic variations of miRNAs were associated with the risk and prognosis of renal cell carcinoma (RCC). We genotyped four common miRNA SNPs (i.e. miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913 and miR-499 rs3746444) to assess their associations with RCC risk in a two-stage case-control study (355 cases and 362 controls in discovery set, meanwhile 647 cases and 660 controls in validation set), as well as RCC survival in 311 patients. We found that the miR-196a2 SNP rs11614913 was associated with RCC susceptibility in recessive model [CC versus TT/TC, adjusted odds ratio = 0.65, 95% confidence interval (CI) = 0.52-0.83] and with survival of RCC in dominant model (TC/CC versus TT, adjusted hazard ratio = 0.40, 95% CI = 0.18-0.89). Meanwhile, the rs11614913 CC genotype was associated with the significantly decreased expression of miR-196a-5p in 26 renal cancer tissues (P = 0.018). Moreover, luciferase reporter assays revealed the potential effect of rs11614913 SNP on the binding of miR-196a-3p to its targets. These results suggested that the miR-196a2 rs11614913 may contribute to the genetic susceptibility and prognosis for RCC, which may act as a biomarker for RCC occurrence and prognosis.

The purpose of this study was to assess the prognostic value of 18F-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) in therapy for non-small cell lung cancer (NSCLC) and to further analyze the possible risk factors contributing to overall survival (OS) and progression-free survival (PFS). We retrospectively analyzed fifty patients between June 2007 and June 2010 with NSCLC who underwent positron emission tomography/computed tomography. We examined the correlation of the maximum standardized uptake value (SUVmax) in FDG-PET of the primary tumor with other possible factors. The FDG uptake in the primary tumor was also compared for the different Union for International Cancer Control (UICC) staging groups and further correlation was analyzed. We divided the patients into two groups by the receiver operating characteristic curve of SUVmax: SUVmax

A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan–Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carry TC/CC genotypes had a significant shorter survival time (log-rank P = 0.005), especially in the subgroups of aged male patients, cardia intestinal tumor (HR = 1.41, 95% CI = 1.08–1.84 for cardia cancer and HR = 1.64, 95% CI = 1.14–2.37 for intestinal-type), tumor size ≤ 5 cm (HR = 1.41, 95% CI = 0.56–0.99), T1 depth invasion (HR = 2.34, 95% CI = 1.20–4.56), lymph node metastasis (HR = 1.51, 95% CI = 1.19–1.96), no distant metastasis (HR = 1.33, 95% CI = 1.05–1.68), TNM stage III + IV (HR = 1.50, 95% CI = 1.13–1.98), and with chemotherapy (HR = 1.53, 95% CI = 1.17–1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population.

Endogenous and exogenous factors can induce DNA damage, leading to increased risk of cancer. Nucleotide excision repair (NER) is considered as the most versatile DNA repair pathway to deal with a variety of different DNA lesions. ERCC1 and ERCC2 are the two important proteins in NER pathway. In this study, we investigated the association of three functional single nucleotide polymorphisms (SNPs) (ERCC1 rs11615, ERCC2 rs13181 and ERCC2 rs1799793) with the clinical outcome of 940 gastric cancer patients in a Chinese population. Multiplex SNaPshot technology was used to genotype these three SNPs. Our results revealed that individuals with ERCC2 rs13181TG/GG genotypes had a decreased risk of death compared with those with TT genotype [log-rank P = 0.008; adjusted hazard ratio = 0.68, 95% confidence interval = 0.51-0.91] and this protective effect was more pronounced among the subgroups of patients with tumour size ≤ 5 cm (0.59, 0.39-0.89), non-cardia gastric tumour (0.69, 0.48-0.98), no lymph node metastasis (0.55, 0.32-0.96), no distant metastasis (0.70, 0.52-0.95) and chemotherapy (0.39, 0.21-0.72). We conclude that ERCC2 rs13181 polymorphism could play different roles in the overall survival of gastric cancer. Further larger studies should be conducted to validate our findings.

Objective Adiponectin (AdipoQ) plays an important role in the pathogenesis of diabetes mellitus and is considered as an important candidate gene for type 2 diabetes mellitus (T2DM). So far, there have been many studies to investigate the association between the adiponectin polymorphisms and T2DM risk. However, the results are conflicting. To derive a more precise estimation, we performed a meta-analysis to assess the association between five AdipoQ polymorphisms [−11426A > G (rs16861194), −11391G > A (rs17300539), −11377C > G (rs266729), +45T > G (rs2241766) and +276G > T (rs1501299)], and T2DM risk. Methods The fixed and random-effects model should be used to assess the summary odds ratios (ORs) of each study. ORs with 95% confidence intervals (CIs) were used to evaluate the strength of association. On the basis of the included criteria, we selected 39 papers, among which eight for −11426A > G, 14 for −11391G > A, 21 for −11377C > G, 28 for +45 T > G and 24 for +276G > T. Sensitivity analyses were conducted to assess the stability of the results. Both Begg's funnel plots and Egger's test are commonly used to evaluate publication bias. Results Overall, we found that individuals with the −11426G allele had a 0.15-fold significantly increased T2DM risk (additive model: 1.15, 1.04–1.27, 0.222). In the stratified analyses, we found that the −11426A > G, −11391G > A and −11377C > G polymorphisms could increase T2DM risk in European populations in the additive model. For Asian populations, we found that the −11377C > G polymorphism also could elevate T2DM risk. Conclusions Our results suggested that the adiponectin −11426A > G polymorphism could contribute to the T2DM risk. Copyright © 2013 John Wiley & Sons, Ltd.

PURPOSE Recently, genetic polymorphism (rs3803662C>T) in TOX3 was reported to induce the risk of breast cancer. In this study, we hypothesized that rs3803662 could influence gastric cancer survival outcomes. METHODS With multiplex SNaPshot method, we genotyped TOX3 rs3803662 in 880 gastric patients with surgical resection. The association between genotype and survival outcomes was performed by the Kaplan-Meier method, Cox regression analysis models and the log-rank test. RESULTS There was no association in the analyses of rs3803662 and survival of gastric cancer. However, the stratified analysis by histology showed that rs3803662 CT/TT genotype was associated with a significantly better survival for diffuse-type gastric cancer (log-rank p = 0.030, hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.46-0.96), than the CC genotype. In addition, this favorable effect was especially obvious among gastric cancer patients with tumor size >5 cm, T3 and T4 depth of invasion, lymph node metastasis, no drinking, no distant metastasis, no chemotherapy and gastric cardia cancer. CONCLUSIONS TOX3 rs3803662 might play an important role in the prognostic outcome and treatment of gastric cancer, especially perhaps further help in explaining the reduced risk of death associated with diffuse-type gastric cancer.

Recent genome-wide association studies (GWAS) that focus on childhood acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15 years old, have found evidence that single nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2) and CEBPE (14q11.2) are strongly related to the risk of childhood ALL. These polymorphisms may lead to abnormal expression and dysfunction of the corresponding transcription factors and are likely to increase the risk of ALL. To validate the relationship between these SNPs and the risk of childhood ALL in Chinese population, we conducted a case-control study of 570 ALL cases and 673 controls. We determined that the SNP rs10821936 in ARID5B was statistically significantly associated with the risk of childhood ALL (P0.0001). The results were also significant for the subgroup analysis of high-risk, medium-risk and low-risk ALL as well as B-lineage ALL. Statistically significant differences were not found in the SNPs for IKZF1 and CEBPE. In conclusion, ARID5B rs10821936 could serve as a potential biomarker for assessing the risk of childhood ALL in Chinese children.

Background In the past decades, a good deal of studies has provided the possibility of the circulating microRNAs (miRNAs) as noninvasive biomarkers for cancer diagnosis. The aim of our study was to detect the levels of circulating miRNAs in tissues and plasmas of gastric cancer (GC) patients and evaluate their diagnostic value. Methods Tissue samples were collected from 85 GC patients. Plasma samples were collected from 285 GC patients and 285 matched controls. Differentially expressed miRNAs were filtered with by Agilent Human miRNA Microarray and TaqMan low density array (TLDA) with pooled samples, followed by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation. Receiver operating characteristic (ROC) curves were structured to evaluate the diagnostic accuracy of the miRNAs. The plasma level of miR-26a in GC patients of different clinical stages was compared. Results Four miRNAs (miR-26a, miR-142-3p, miR-148a, and miR-195) revealed coincidentally decreased levels in tissue and plasma of the GC patients compared with controls, and ROC curves were constructed to demonstrate that miR-26a had a highest area under the ROC curve (AUC) of 0.882. Furthermore, miR-26a was stably detected in the plasma of GC patients with different clinical characteristics. Conclusion Plasma miR-26a may provide a novel and stable marker of gastric cancer.

MicroRNAs (miRNAs) are a family of endogenous, small, noncoding RNA molecules that involved in a wide range of biological processes including differentiation, proliferation, and apoptosis. A polymorphism G>C (rs2910164) is located in the stem region opposite to the mature miR-146a sequence. In our study, we investigated whether rs2910164 is associated with the risk of colorectal cancer (CRC) in a Chinese population. We genotyped the rs2910164 polymorphism using TaqMan method and evaluated the association with CRC risk in a case–control study, including 1,147 CRC patients and 1,203 cancer-free controls. Logistic regression models were used to assess the genetic effects on the development of CRC. Overall, we found that rs2910164 was significantly associated with the reduced CRC risk [GC/CC versus GG: adjusted odds ratio (OR) = 0.78, 95 % confidence intervals (CIs) = 0.66–0.93]. In the stratification analysis, this decreased risk was also pronounced among non-smokers (0.75, 0.61–0.93), non-drinkers (0.77, 0.63–0.94), and no family history of cancer (0.79, 0.65–0.95). Furthermore, GC/CC genotypes were associated with reduced CRC susceptibility in intermediate differentiated CRC (0.75, 0.62–0.90), and similar effect was observed in patients with the advanced stage tumor (Dukes C and D) (0.76, 0.61–0.93). In conclusion, our results suggest that miR-146a rs2910164 may contribute to the susceptibility to CRC in a Chinese population. Further larger population-based prospective and functional studies are needed to validate our findings.

Evidence has shown that miR-146a is involved in carcinogenesis, and a common G/C variant (rs2910164) in the pre-miR-146a gene has been associated with various types of cancer. We summarized the data from 22 published case-control studies on the association between rs2910164 and cancer risk and performed subgroup analyses by ethnicity, gender and smoking status. We found a significant association between the pre-miR-146a polymorphism and cancer risk in Caucasian populations (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.88-0.99 for G- vs C-allele), while the significance was borderline in Asian populations (OR = 1.11, 95%CI = 1.00-1.23 for G- vs C-allele). A significantly increased risk of cancer was found in males with GG/GC genotypes (OR = 1.23, 95%CI = 1.10- 1.37), and the significance was more pronounced in smokers (OR = 1.82, 95%CI = 1.32-2.51) than in non-smokers (OR = 1.24, 95%CI = 1.01-1.53). We conclude that there is evidence that the pre-miR-146a polymorphism contributes to cancer susceptibilities and that gender and smoking status affect the probability of cancer in individuals with this polymorphism.

miRNAs play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. Because altered expression and function of miRNAs has been observed in bladder cancer, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single-nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA–disease associations in a two-stage model, consisting of 1,019 bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets, as well as the combined set [OR = 0.80, 95% confidence interval (CI) = 0.71–0.90, P = 2.92 × 10−4]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and TRAF6 in bladder cancer cells. Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer, suggesting it may represent a biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings. Cancer Res; 72(23); 6173–82. ©2012 AACR.

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-aa protein related to the cell-proliferation inhibition and/or cell-death induction activity. Many studies had reported the role of PSCA rs2294008 C > T and rs2976392 G > A polymorphisms on gastric cancer risk. To investigate a more precise estimation of the relationships, we performed a meta-analysis on 9 case–control studies included 10,746 cases and 9,158 controls. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the association. For PSCA rs2294008 C > T polymorphism, there was a significantly increased risk of gastric cancer in all genetic models (TT/TC vs. CC: OR = 1.61, 95 % CI = 1.35–1.91; TT vs. TC/CC: OR = 1.33, 95 % CI = 1.24–1.42). Similar results were also observed for PSCA rs2976392 G > A polymorphism (AA/AG vs. GG: OR = 1.69, 95 % CI = 1.24–2.31; AA vs. AG/GG: OR = 1.36, 95 % CI = 1.24–1.50). In the stratified analysis by ethnicity of rs2294008, an increased gastric cancer risk was found in both Asians (TT vs. TC/CC: OR = 1.31, 95 % CI = 1.22–1.42) and Europeans (TT/TC vs. CC: OR = 1.42, 95 % CI = 1.18–1.71). Furthermore, when stratified by clinicopathologic characteristics of tumor location and histology, a higher risk on non-cardia compared with cardia gastric cancer (TT vs. TC/CC: OR = 1.43, 95 % CI = 1.12–1.83) as same as diffused compared with intestinal gastric cancer (TT vs. TC/CC: OR = 1.29, 95 % CI = 1.13–1.49) was observed. These findings supported that PSCA rs2294008 C > T and rs2976392 G > A polymorphisms may contribute to the susceptibility to gastric cancer, particular in non-cardia or diffused gastric cancer.

BACKGROUND: Alcohol dehydrogenase 1C (ADH1C) is the key enzyme catalyze oxidation of alcohol to acetaldehyde, which plays vital roles in the etiology of various cancer. To date, studies investigated the association between a functional polymorphism in ADH1C, Ile350Val (rs698), and risk of cancer have shown inclusive results. METHODS: A meta-analysis based on 35 case-control studies was performed to address this issue. Odds ratios (OR) with 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with χ2-based Q-test. RESULTS: Overall, no significant associations between ADH1C Ile350Val polymorphism and cancer risk were observed in any genetic models (P>0.05). In the stratified analyses, there was a significantly increased cancer risk among African (Val/Val vs. Ile/Ile OR = 2.19, 95% CI = 1.29-3.73, P(heterogeneity) = 0.989; Ile/Val + Val/Val vs. Ile/Ile: OR = 1.79, 95%CI = 1.18-2.71, P(heterogeneity) = 0.761; Val/Val vs. Ile/Val + Ile/Ile: OR = 1.92, 95% CI = 1.16-3.17, P(heterogeneity) = 0.981) and Asian (Ile/Val vs. Ile/Ile: OR = 1.58, 95% CI = 1.32-1.90, P(heterogeneity) = 0.375; Val/Val vs. Ile/Ile: OR = 3.84, 95% CI = 1.74-8.49, P(heterogeneity) = 0.160; Ile/Val + Val/Val vs. Ile/Ile: OR = 1.65, 95% CI = 1.38-1.96, P(heterogeneity) = 0.330; Val/Val vs. Ile/Val + Ile/Ile: OR = 3.54, 95% CI = 1.62-7.75, P(heterogeneity) = 0.154) studies. CONCLUSIONS: The results indicate that ADH1C Ile350Val polymorphism may contribute to cancer risk among Africans and Asians. Additional comprehensive system analyses are required to validate this association combined with other related polymorphisms.

The mammalian target of rapamycin (mTOR) is an important protein kinase regulating cell survival and apoptosis. To determine whether genetic variations in mTOR are associated with risk of acute lymphoblastic leukemia (ALL) in Chinese children, we genotyped two tag single nucleotide poymorphisms (SNPs) in mTOR (rs2536 and rs2295080) in a case–control study. We observed that the variant genotype TC of mTOR rs2536 was associated with a significantly decreased risk of childhood ALL (adjusted odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.46–0.96), and the association was more pronounced in high-risk ALL and T-phenotype ALL groups. Additionally, we found that the combined genotypes TC/CC decreased the risk of ALL only in the high-risk ALL group (adjusted OR = 0.54, 95% CI = 0.32–0.91) and T-phenotype ALL group (adjusted OR = 0.29, 95% CI = 0.10–0.84). These results suggest that the mTOR rs2536 polymorphism is involved in the susceptibility to childhood ALL in a Chinese population.

Nonsyndromic orofacial clefts (NSOC) are one of the most common congenital anomalies in humans. Great efforts have been taken to unravel its genetic background. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism and two of its functional polymorphisms, MTHFR C677T and MTHFR A1298C, might be associated with NSOC susceptibility. The aim of the present study was to investigate their associations with risks of NSOC in a southern Chinese population. We found that MTHFR 677 TT and 677 CT/TT were associated with increased risk of cleft lip with or without cleft palate; meanwhile, MTHFR 1298 AC and 1298 AC/CC had protective effects against cleft lip with or without cleft palate. In further stratified analysis, we found that MTHFR 677 CT contributed to elevated risk of cleft lip only, as did MTHFR 677 CT/TT. On the contrary, MTHFR 1298 AC and 1298 AC/CC appeared to be protective against cleft lip with cleft palate. These results suggested that these two polymorphisms were involved in the development of NSOC in a southern Han Chinese population.

Oxidative DNA damage caused by reactive oxygen species can produce 8-oxoguanine (8-oxoG) in DNA, which is misread and leads to G:CT:A transversions. This can be carcinogenic. Repair of 8-oxoG by the base excision repair pathway involves the activity of human 8-oxoG DNA glycosylase 1 (hOGG1). Accumulating evidence suggests that the hOGG1 Ser326Cys polymorphism affects the activity of hOGG1 and might serve as a genetic marker for susceptibility to several cancers. To determine whether this polymorphism is associated with risk of childhood acute lymphoblastic leukemia (ALL) in Chinese children, we genotyped the hOGG1 Ser326Cys polymorphism (rs1052133) in a case–control study including 415 cases and 511 controls. We found that there was a significant difference in the genotype distributions of the hOGG1 Ser326Cys polymorphism between cases and controls (P = 0.046), and the combined genotypes Ser/Ser and Ser/Cys were associated with a statistically significantly decreased risk of ALL (adjusted odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.49–0.88, P = 0.005). Furthermore, we found a decreased risk for high risk ALL (adjusted OR = 0.60, 95% CI = 0.40–0.88, P = 0.005), low risk ALL (adjusted OR = 0.68, 95% CI = 0.47–0.99, P = 0.042), and B-phenotype ALL (adjusted OR = 0.63, 95% CI = 0.46–0.86, P = 0.003) among children with the Ser/Ser and Ser/Cys genotypes. Our results suggest that the hOGG1 Ser326Cys polymorphism is associated with susceptibility to childhood ALL in a Chinese population. (Cancer Sci 2011; 102: 1123–1127)

Background Fibroblast growth factor receptor 4 (FGFR4) displays multiple biological activities, including mitogenic and angiogenic activity, and plays important roles in the etiology and progression of prostate cancer. Gly388Arg polymorphism in FGFR4 gene has been reported to be involved in prostate cancer incidence and aggressiveness in several studies. To derive a more precise estimation of the relationship, a meta-analysis was performed. Methods Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Results The Arg388 allele increased prostate cancer risk compared with Gly388 allele (OR = 1.17, 95% CI = 1.07-1.29). When stratified by race, there was a significantly increased prostate cancer risk in Asian and Caucasian populations. Moreover, prostate cancer patients with Arg/Arg genotype had a 1.34-fold increased risk of advanced prostate cancer (95% CI: 1.03-1.74) compared with those with Gly/Gly+Gly/Arg genotype. Conclusion This meta-analysis showed the evidence that FGFR4 Gly388Arg polymorphism was associated with an increased risk of prostate cancer development and progression, suggesting that FGFR4 Gly388Arg polymorphism could be a marker for prostate cancer development and progression.

BACKGROUND To explore the reported association of SNP marker rs10993994 with prostate cancer identified by two independent in two genome-wide association studies (GWAS) further, we performed a case–control study in southern Chinese Han population. Consequently, we detected the serum levels of MSMB expression with different genotypes in the cases and controls to characterize the functional consequences of rs10993994. MATERIALS AND METHODS Two hundred fifty-one prostate cancer and 258 control subjects were included in the cancer association study and 90 serum samples were used to test the expression of the MSMB by Enzyme-linked immunosorbent assay (ELISA). RESULTS We found that the T allele displayed an increased prevalence of prostate cancer compared with the C allele (OR = 1.30, 95% CI = 1.01–1.67, P = 0.040). Moreover, the prostate cancer patients carrying CT/TT genotype had significantly decreased serum MSMB levels compared to those with CC genotype (16.32 ± 3.98 µg/L vs. 19.33 ± 4.27 µg/L, P = 0.022). CONCLUSIONS rs10993994 in MSMB promoter affects serum MSMB expression, contributes to the genetic predisposition to prostate cancer in southern Chinese Han population. Prostate 70: 1146–1152, 2010. © 2010 Wiley-Liss, Inc.