Macrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer . Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.

The retinoic acid receptor beta2(RAR beta 2) is a type of nuclear receptor that is activated by both all-trans retinoic acid and 9-cis retinoic acid, which has been shown to function as a tumor suppressor gene in different types of human tumors. Previous reports demonstrated that the frequency of RAR beta 2 methylation was significantly higher in prostate cancer patients compared with controls, but the relationship between RAR beta 2 promoter methylation and pathological stage or Gleason score of prostate cancer remained controversial. Therefore, a meta-analysis of published studies investigating the effects of RAR beta 2 methylation status in prostate cancer occurrence and association with both pathological stage and Gleason score in prostate cancer was performed in the study. A total of 12 eligible studies involving 777 cases and 404 controls were included in the pooled analyses. Under the random-effects model, the pooled OR of RAR beta 2 methylation in prostate cancer patients, compared to non-cancer controls, was 17.62 with 95%CI = 6.30-49.28. The pooled OR with the fixed-effects model of pathological stage in RASSF1A methylated patients, compared to unmethylated patients, was 0.67 (95%CI = 0.40-1.09) and the pooled OR of low-GS in RAR beta 2 methylated patients by the random-effect model, compared to high-GS RAR beta 2 methylated patients, was 0.54 (95% CI = 0.28-1.04). This study showed that RAR beta 2 might be a potential biomarker in prostate cancer prevention and diagnosis. The detection of RAR beta 2 methylation in urine or serum is a potential non-invasive diagnostic tool in prostate cancer. The present findings also require confirmation through adequately designed prospective studies.

MicroRNAs (miRNAs) are a class of small non-protein-coding RNAs, which have emerged as integrated and important post-transcriptional regulators of gene expression. It has been demonstrated that single nucleotide polymorphisms (SNPs) exist in protein-coding genes. Accumulated studies have evaluated the association of miRNA SNPs with cancer risk, especially in Asian population, which included a series of related studies. However, the results remain controversial for the different genetic backgrounds, living habits and environment exposed. To evaluate the relationship between SNPs in miRNAs and cancer risk, 21 studies focused on Asian population were enrolled for the pooled analysis for three polymorphisms rs2910164, rs11614913, rs3746444 in three miRNAs miR-146aG>C, miR-196a2C>T, miR-499A>G using odds ratios (ORs) with 95% confidence intervals (CIs). For rs2910164 polymorphism, C allele was observed association with decreased overall cancer risk. In addition, subgroup analysis revealed of rs2910164 C allele decreased hepatocellular carcinoma (HCC), cervical cancer and prostate cancer risk among Chinese population. For rs11614913 polymorphism, TT genotype was observed to be associated with decreased cancer risk, especially for cancer type of colorectal cancer (CRC), lung cancer and country of Korea, North India. Whereas, rs3746444 G allele was an increased cancer risk factor in Chinese population, especially for breast cancer. In conclusion, this meta-analysis indicated that rs2910164 C allele was associated with decreased cancer risk in Chinese population. However, the association varied from different cancer types. Furthermore, TT genotype of rs11614913 was associated with decreased cancer risk. While different cancer types and countries contributed to different effects. Whereas, rs3746444 G allele was a risk factor in Chinese population, and the association varied from different cancer types.

OBJECTIVE:To investigate the effect of epithermal growth factor receptor (EGFR) expression and K-ras, B-raf and PIK3CA mutation status on the radiosensitivity of human colorectal carcinoma (CRC) cell lines in vitro. METHODS:Real-time RT-PCR was used to measure EGFR mRNA expression in nine human CRC cell lines, and K-ras, B-raf and PIK3CA mutation status of each CRC cell line was also identified respectively. After treatment with irradiation at graded dose, the cell viability was measured by clonogenic survival assay. The rate of cell apoptosis and cell cycle distribution were tested by flow cytometry. The cell morphology was observed with hoechst 33258 staining to analyze the correlation between EGFR mRNA expression and radiosensitivity of CRC cell lines. RESULTS:A positive correlation between EGFR mRNA expression and survival fraction of 2 Gy(SF2) was observed (r=0.717, P=0.030). Association was also identified between the mutation status of PIK3CA and radiosensitivity (t=2.401, P=0.047), while mutation status of K-ras and B-raf was not associated with radiosensitivity. At 48-hour after exposing to irradiation, the apoptosis rate of radiosensitive cell line (HCT116) was significantly increased in a dose-dependent manner (P<0.05), while the apoptosis rate of radioresistant cell line (HT29) was significantly increased only when radiation dose increased to 6 Gy. The ratio of G0/G1 phase was reduced significantly with the increase of radiation dose in radiosensitive cell line (HCT116, P<0.05), while this trend was not observed in radioresistant cell line (HT29, P>0.05). CONCLUSIONS:Over-expression of EGFR mRNA is correlated to radioresistance of human CRC cell lines, and mutation status of PIK3CA is closely related with radiosensitivity of CRC cells. The inhibition of apoptosis and G0/G1 arrest may induce the radioresistance of CRC cell lines.

MicroRNA-21 (miR-21) has been ascribed a key role in many cellular processes, e.g. tumorigenesis via inhibition of target gene expression. However, its role in diffuse large B-cell lymphoma (DLBCL) is still unclear, and there are no in-depth studies on the relationship between miR-21 and the cellular phenotype of DLBCL. In this study, we investigated the expression and role of miR-21 in the regulation of cell biological processes in DLBCL. Firstly, miR-21 expression was evaluated in three DLBCL cell lines by real-time quantitative reverse-transcription (qRT) polymerase chain reaction (PCR). Then, to determine the possible role of miR-21 in the biological and behavioral characteristics of DLBCL, we performed miR-21 knockdown by transfection with anti-miR-21. In addition, PDCD4 and PTEN were assessed by luciferase reporter assay, qRT-PCR, and Western blot. Our study revealed that miR-21 was significantly upregulated in activated B-cell-like DLBCL cells compared to germinal center-like DLBCL cells. We demonstrated that inhibition of miR-21 induced suppression of proliferation and invasion, as well as increased apoptosis in DLBCL. Moreover, knockdown of miR-21 increased PDCD4 and PTEN expression at the protein level but not at the mRNA level. In conclusion, miR-21 can regulate proliferation, invasion, and apoptosis, and thus it has a potential therapeutic application in DLBCL.

Adiponectin produced by adipose tissue, which is involved in complex diseases related to obesity, such as cancer. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. However, epidemiological results were inconsistent. To examine this controversy, we assessed reported studies of association between ADIPOQ polymorphisms and cancer risk. Relevant studies were selected by PUBMED, EMBASE update to January 12th, 2012. According to the acceptance and exclusion criteria, 15 studies involved three polymorphisms (rs266729, rs2241766, rs1501299) of ADIPOQ were included. Summary odds ratio (ORs) and 95 % confidence intervals (CIs) were calculated using random-effect or fixed-effect models based on the heterogeneity of included studies. A total of 15 case–control studies related rs266729 (5,615 cases and 6,425 controls), rs2241766 (5,318 cases and 6,118 controls) and rs1501299 (3,751 cases and 5,104 controls) were included to analyze the ADIPOQ polymorphisms and cancer risk. For rs1501299, T allele was associated with decreased cancer risk. In addition, cancer type subgroup analysis revealed T allele was associated with decreased colorectal and prostate cancer risk. Ethnicity subgroup analysis observed a decreased risk in both Asian and Caucasian descendents. As to rs2241766, a borderline decreased cancer risk was observed. This meta-analysis indicated T allele of rs1501299 was an obvious protection factor for cancer risk, and G allele of rs2241766 was a potential protection factor for cancer risk, especially in Caucasian descendents. Further studies should be performed to clarify the roles of ADIPOQ polymorphisms in the cancer risk.

IL1B(Interleukin 1beta) is a pro-in?ammatory cytokine against infection,playing an important role in the growth of cancers.The-31T/C polymorphism sites of the IL1B gene promoter region have participated in cancer occurrence through its in?uence on IL1B transcription.However,informed reasearch has different results.To clarify the association,a meta analysis has been performed for 11125 cases and 14415 controls from 47 published case–control studies.Odds ratio(OR) and 95% con?dence interval(CI) could assess connection degree of polymorphic site and cancer risk.The polymorphic site has not connected with all cancers in all comparisons.Through strati?ed analyses,the individual carrying C allele has lower risk than non-carrier(CC vs TT: OR = 0.87,95%CI: 0.77~0.98,Pheterogeneity= 0.103;TC vs TT: OR = 0.77,95%CI: 0.62~0.95,Pheterogeneity = 0.734;TC+CC vs TT: OR = 0.74,95%CI: 0.61~0.91,Pheterogeneity = 0.472).Similarly,the T/T genotype individual is easier to get gastric cancer compared with the C/C genotype(OR = 0.87,95%CI: 0.77~0.98,Pheterogeneity = 0.103).Using the recessive model,the risk of gastric cancer observably reduces(OR = 0.88,95%CI: 0.80~0.97,Pheterogeneity = 0.158).In european population(OR = 0.84,95%CI: 0.73~0.97,Pheterogeneity = 0.070) and infection-matched studies(OR = 0.75,95%CI: 0.60~0.94,Pheterogeneity = 0.220),the risk also notablely decreases;however,an increasing risk is found from breast cancer(OR=1.34,95%CI: 1.18~1.61,Pheterogeneity =0.116).Although some modest biases could not be eliminated,this meta-analysis shows that the IL1B-31C allele is a protective factor for cancer,particularly the infections.

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development with changes in the microRNA's properties and/or maturation. Polymorphisms in miRNAs have been suggested in predisposition to cancer risk; however, accumulated studies have shown inconsistent conslusionss. To further validate determine whether there is any potential association between the four common SNPs (miR-196a2C>T, rs11614913; miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the risk for developing risk, a meta-analysis was performed according to the 40 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the extent of the association. The results demonstrated that the rs11614913TT genotype was significantly associated with a decreased cancer risk, in particular with a decreased risk for colorectal cancer and lung cancer, or for Asian population subgroup. In addition, the rs2910164C allele was associated with decreased risk for esophageal cancer, cervical cancer, prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian population subgroup. Similarly, the rs3746444G allele was observed as a risk factor for cancers in the Asian population. It is concluded that two SNPs prsent in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of some cancers, and that the rs3746444 may increase risk for cancer.

OBJECTIVE:To explore the correlation between the polymorphism in the DNA methyltransferase-3B (DNMT3B) gene promoter single nucleotide polymorphism (SNP)-149C→T (rs2424913) and-579G→T(rs1569686) and the genetic susceptibility to colorectal cancer in Jiangsu population.METHODS:Genomic DNA was extracted from the leukocyte cell of blood samples collected from 544 colorectal cancer (CRC) patients (including 280 cases of colon cancer and 264 cases of rectal cancer) since January 2009 and July 2010, in a hospital, Jiangsu Province. The same samples were collected from the other 533 control subjects. Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis were employed to assess the polymorphism of DNMT3B gene promoter-149C→T and-579G→T.RESULTS:For DNMT3B-149C→T, no significant deviation was observed in the genotype distributions of polymorphisms between CRC cases (TT: 98.90% (538/544); CT: 1.10% (6/544)) and controls (TT: 97.75% (521/533); CT: 2.25% (12/533)) (χ(2) = 2.07, P = 0.15). The CC genotype was not detected in either patients or control subjects. The DNMT3B-149CT genotype was not associated with the risk of CRC (adjusted OR = 0.48, 95%CI: 0.18 - 1.30). For DNMT3B-579G→T, the genotype distributions of polymorphisms in CRC patients (TT: 90.07% (490/544); GT: 9.19% (50/544); GG: 0.74% (4/544)) were significantly different from those in control group (TT: 81.80% (436/533); GT: 17.82% (95/533); GG: 0.38% (2/533)) (χ(2) = 15.49, P < 0.05). The results showed that the-579 G allele could significantly decrease the risk of CRC (adjusted OR = 0.50, 95%CI: 0.35 - 0.72) in comparison with the -579 TT genotype. In addition, stratification analysis showed that for DNMT3B-579G→T, the genotype distributions of polymorphisms in colon cancer (TT: 92.50% (259/280); GT: 7.50% (21/280)) were significantly different from those in the controls (TT: 81.80% (436/533); GT: 17.82% (95/533); GG: 0.38% (2/533)) (χ(2) = 13.53, P < 0.05); and similar result was found in rectal cancer (TT: 87.50% (231/264); GT: 10.98% (29/264); GG: 1.52% (4/264)) and controls (TT: 81.80% (436/533); GT: 17.82% (95/533); GG: 0.38% (2/533)) (χ(2) = 5.64, P = 0.018). G allele carriers could decrease the risk of colon cancer (adjusted OR = 0.38, 95%CI: 0.23 - 0.63), and the risk of rectal cancer (adjusted OR = 0.65, 95%CI: 0.42 - 0.99). However, for DNMT3B-149C→T , there were no significant deviation in the genotype distributions of polymorphisms between colon cancer (TT: 98.57% (276/280); CT: 1.43% (4/280)) and controls (TT: 97.75% (521/533); CT: 2.25% (12/533)) (χ(2) = 0.82, P = 0.366); and there was no significant deviation between rectal cancer (TT: 99.24% (262/264); CT: 0.76% (2/264)) and controls (TT: 97.75% (521/533); CT: 2.25% (12/533)) either (χ(2) = 1.89, P = 0.169).CONCLUSION:Our research demonstrates that the-579 G allele is a potential protective factor for the occurrence of CRC, however, the polymorphism of DNMT3B-149 gene shows no close correlation with the occurrence and development of CRC among Chinese population.

Leptin and leptin receptor have been implicated in processes of breast cancer.An A to G transition of codon 223th in exon 6 of leptin receptor gene(LEPR) can result in the substitution from glutamine to arginine(Gln223Arg).A variety of case–control papers have been published to evaluate the association between LEPR Gln223Arg polymorphism and breast cancer.However,they have got contradictory conclusions.This meta analysis enrolls 8 papers to evaluate the connection of them.The pooled ORs are took for codominant model,recessive model,dominant model.The result shows that recessive model(OR=1.32,95%CI: 1.03~1.69) and genotype Arg/Gln vs Gln/Gln(OR=1.16,95%CI: 1.01~1.34) significantly improve breast cancer risk in overall study.In racial stratified analysis,some genotypes among Africans would significantly increase the risk: Arg/Arg vs Gln/Gln(OR=1.86,95%CI: 1.28~2.71),Arg/Gln vs Gln/Gln(OR=1.48,95%CI: 1.10~1.99),dominant model(OR=1.60,95%CI: 1.21~2.11) and recessive model(OR=1.48,95%CI: 1.07~2.05);for Asians,Arg/Arg vs Gln/Gln(OR=6.79,95%CI: 3.42~13.47) and dominant model(OR=2.03,95%CI: 1.42~2.90).However,no genetic models are found among Europeans which significantly increase cancer risk.In conclusion,the LEPR 223Arg is a low risk factor for developing breast cancer,especially for African women.

RAS association domain family protein 1a (RASSF1A) is a putative tumor suppressor gene located on 3p21, has been regarded playing important roles in the regulation of different types of human tumors. Previous reports demonstrated that the frequency of RASSF1A methylation was significantly higher in patients group compared with controls, but the relationship between RASSF1A promoter methylation and pathological features or the tumor grade of bladder cancer remains controversial. Therefore, A meta-analysis of published studies investigating the effects of RASSF1A methylation status in bladder cancer occurrence and association with both pTNM (p, pathologic stage; T, tumor size; N, node status; M, metastatic status) and tumor grade in bladder cancer was performed in the study. A total of 10 eligible studies involving 543 cases and 217 controls were included in the pooled analyses. Under the fixed-effects model, the OR of RASSF1A methylation in bladder cancer patients, compared to non-cancer controls, was 8. 40 with 95%CI=4. 96-14. 23. The pooled OR with the random-effects model of pTNM and tumor grade in RASSF1A methylated patients, compared to unmethylated patients, was 0. 75 (95%CI=0. 28-1. 99) and 0. 39 (95%CI=0. 14-1. 09). This study showed that RASSF1A methylation appears to be an independent prognostic factor for bladder cancer. The present findings also require confirmation through adequately designed prospective studies.

Objective To derive a more precise conclusion of the association between Cox-2 and tumor.Methods Through literature retrieval,to collect control studies of 25 cases,including 9482 tumor cases and 12206 controls.By meta analysis for previous research results,we use odds ratios(OR) and 95% confidence intervals(CI) to assess the strength of the association between gene and tumors.Results The mutational genotypes moderately increase risk of cancer(AA/AG vs GG,OR=1.15,95%CI: 1.02~1.31).According to population stratification display,a mutation genotype could increase risk in Asian population(AA/AG vs GG,OR=1.28,95%CI: 1.12~1.46),but no significant association between genic mutation and cancer,except oesophageal cancer group and "other" groups when stratified by tumor type.Conclusion The meta analysis indicates that Cox2-1195G > A may be a potential risk factor for tumor.

Objective To conclude the association between OGG1 Ser326Cys polymorphism and colorectal cancer(CRC).Methods This meta analysis enrolls 12 papers to estimate the risk of OGG1 Ser326Cys polymorphism associated with CRC morbidity.The pooled odds ratio(OR) is performed for dominant model(Cys/Cys vs Ser/Ser;Ser/Cys vs Ser/Ser),leading model(Ser/Cys+Cys/Cys vs Ser/Ser) and recessive model(Cys/Cys vs Ser/Cys+Ser/Ser).Results No significant associations are found among Cys/Cys vs Ser/Ser(OR=1.19,95%confidence interval(CI)=0.92~1.53),Ser/Cys vs Ser/Ser(OR=1.04,95%CI=0.95~1.13),Ser/Cys+Cys/Cys vs Ser/Ser(OR=1.06,95%CI=0.98~1.16) and Cys/Cys vs Ser/Cys+Ser/Ser(OR=1.11,95%CI=0.90~1.38),moreover,in stratified analysis,no significant differences in risk are found in all genetic models.Conclusion meta analysis indicates that OGG1 Ser326Cys polymorphism do not associate with CRC morbidity.

Interleukin 1β (IL-1B) is a pro-inflammatory cytokine against infection, playing an important role in the pathogenesis of cancers. The -31T/C polymorphism of the interleukin 1β gene (IL1B) has been implicated in cancer risk through its influence on the IL1B transcription. However, results from studies are conflicting. To clarify the association, a meta-analysis was performed for 11 125 cases and 14 415 controls from 47 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. No significant associations were observed for total cancer from all the comparisons. Through the stratified analyses, there was a statistically significant decreased risk of hepatocellular cancer in carriers of the C allele than non-carriers (CC versus TT: OR = 0.87, 95% CI: 0.77-0.98, P(heterogeneity) = 0.103; TC versus TT: OR = 0.77, 95% CI: 0.62-0.95, P(heterogeneity) = 0.734; TC + CC versus TT: OR = 0.74, 95% CI: 0.61-0.91, P(heterogeneity) = 0.472). Similarly, decreased risk was observed for gastric cancer of the C/C genotype compared with the T/T genotype (OR = 0.87, 95% CI: 0.77-0.98, P(heterogeneity) = 0.103). Using the recessive model, a significantly decreased risk was observed for gastric cancer (OR = 0.88, 95% CI: 0.80-0.97, P(heterogeneity) = 0.158), European population (OR = 0.84, 95% CI: 0.73-0.97, P(heterogeneity) = 0.070) and positive infection-matched studies (OR = 0.75, 95% CI: 0.60-0.94, P(heterogeneity) = 0.220); however, an increased risk was found for breast cancer (OR = 1.34, 95% CI: 1.18-1.61, P(heterogeneity) = 0.116). Although some modest bias could not be eliminated, this meta-analysis suggests that the IL1B -31C allele is a low-penetrance protective factor for the development of cancer, in particular for that associated with infection.