Adiponectin (ADIPOQ) is a cytokine produced by adipose tissue involved in carcinogenesis. ADIPOQ SNP rs2241766 has been extensively studied in colorectal cancer (CRC) community with contentious and conflicting conclusions. The objective of this study was to comprehensively assess the association between SNP rs2241766 and CRC risk. PubMed, Embase, CNKI, as well as the references of the retrieved articles were searched to identify the eligible studies for this meta-analysis. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the association. We also examined the heterogeneity and publication bias and performed sensitivity analyses. Seven studies with 2,414 cases and 2,796 controls together did not show any significant association between SNP rs2241766 and CRC risk. Subgroup analyses by ethnicity and sample size also failed to provide statistically significant evidence. This meta-analysis demonstrates that ADIPOQ SNP rs2241766 may not represent as an effect modifier for the risk of CRC.

Previous studies proposed that CYP1A2 rs762551 polymorphism might be associated with risk of lung cancer by influencing the function of CYP1A2. However, previous studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer reported inconsistent findings. We performed a meta-analysis of the published case-control studies to assess the association between CYP1A2 rs762551 polymorphism and risk of lung cancer. PubMed and Embase were searched to identify relevant studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer, and seven studies with a total of 3,320 subjects were finally included into the meta-analysis. The pooled odds ratio (OR) and 95 % confidence interval (95%CI) was calculated to evaluate the association. Meta-analysis of total studies showed that CYP1A2 rs762551 polymorphism contributed to risk of lung cancer under all four genetic models (C versus A: OR = 1.26, 95%CI 1.13 to 1.40, P < 0.001; CC versus AA: OR = 1.61, 95%CI 1.28 to 2.04, P < 0.001; CC versus AA/AC: OR = 1.52, 95%CI 1.11 to 2.09, P = 0.009; CC/AC versus AA: OR = 1.28, 95%CI 1.10 to 1.48, P = 0.001). Subgroup analysis based on ethnicity further suggested that CYP1A2 rs762551 polymorphism was associated with risk of lung cancer in Caucasians. These results from the meta-analysis suggest that CYP1A2 rs762551 polymorphism contributes to risk of lung cancer.

Radiotherapy is an important weapon in the treatment of breast cancer, but normal tissue injury after radiotherapy can be a threat for patients. Genetic markers conferring the ability to identify hyper-sensitive patients at risk of normal tissue injury in advance would considerably improve therapy. Association studies on genetic variation and occurrence of normal tissue injury can help us identify such markers, but previous studies on the association between XRCC1 R399Q polymorphism and risk of normal tissue injury after radiotherapy in breast cancer patients report conflicting findings. We performed a meta-analysis to comprehensively evaluate the association between XRCC1 R399Q polymorphism and risk of normal tissue injury after radiotherapy in breast cancer patients. The pooled odds ratios (ORs) with their 95% confidence interval (95% CIs) were calculated to assess the strength of the association. Fourteen case-control studies with a total of 2,448 breast cancer cases were finally included into the meta-analysis. Overall, XRCC1 R399Q polymorphism was significantly associated with increased risk of normal tissue injury after radiotherapy under all three models (for QQ versus RR: fixed-effects OR = 1.06, 95% CI 1.00-1.13, P = 0.050; for RQ versus RR: fixed-effects OR = 1.05, 95% CI 1.00-1.10, P = 0.047; for QQ/RQ versus RR: fixed-effects OR = 1.26, 95% CI 1.01-1.58, P = 0.041). The meta-analysis suggests that XRCC1 R399Q polymorphism was significantly associated with increased risk of normal tissue injury after radiotherapy in breast cancer patients, and XRCC1 R399Q polymorphism is a genetic marker of normal tissue injury after radiotherapy in breast cancer patients.

Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.

The diagnostic and prognostic value of microRNA (miRNA) expression aberrations in pancreatic ductal adenocarcinoma (PDAC) has been studied extensively in recent years. However, differences in measurement platforms and lab protocols as well as small sample sizes can render gene expression levels incomparable.

Single nucleotide polymorphisms (SNPs) occurring in Toll-like receptors (TLRs) may contribute to cancer risk. Many polymorphisms of TLR2 have been studied for associations, but the findings are conflicting.

The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results of previous meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-control datasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixed- effect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as well as in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A, OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample and rigorous studies are needed to validate the findings.

Colorectal cancer is the third most common cancer in both men and women in the world and the second leading cause of cancer-related deaths. The incidence of colorectal cancer has increased in Iran in the past three decades and is now considered as a serious problem for our society. This cancer has two types hereditary and non-hereditary, 80% of cases being the latter. Considering that the relationship between SNPs with diseases is a concern, many researchers believed that they offer valuable markers for identifying genes responsible for susceptibility to common diseases. In some cases, they are direct causes of human disease. One SNP can increase risk of cancer, but when considering the rate of overlap and frequency of DNA repair pathways, it might be expected that SNP alone cannot affect the final result of cancer, although several SNPs together can exert a significant influence. Therefore identification of these SNPs is very important. The most important loci which include mutations are: MLH1, MSH2, PMS2, APC, MUTYH, SMAD7, STK11, XRCC3, DNMT1, MTHFR, Exo1, XRCC1 and VDR. Presence of SNPs in these genes decreases or increases risk of colorectal cancer.

Published studies on the association between methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G401A polymorphism and ovarian cancer risk have yielded conflicting results. In order to derive a more precise estimation of the relationship between G401A polymorphism and ovarian cancer risk, the present meta-analysis was performed. All eligible studies on G401A polymorphism and ovarian cancer risk were collected from the PubMed and the Cochrane Library. Statistical analyses were performed by Review Manage 5.0 and Stata 11.0. Our analysis suggested that G401A polymorphism was not associated with ovarian cancer risk when using additive (odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.34-2.20, P < 0.0001), recessive (OR = 1.46, 95% CI = 1.21-1.77, P < 0.0001), dominant (OR = 1.36, 95% CI = 1.10-1.69, P = 0.004), and allelic models (OR = 1.30, 95% CI = 1.15-1.47, P < 0.0001) to analyze the data. This meta-analysis suggests that G401A polymorphism might not be a risk factor for ovarian cancer risk. However, further well-designed studies are required to confirm our findings.

We aimed to shed new light on the roles of microRNAs (miRNAs) in liver cancer using an integrative in silico bioinformatics analysis. A new protocol for target prediction and functional analysis is presented and applied to the 26 highly differentially deregulated miRNAs in hepatocellular carcinoma. This framework comprises: (1) the overlap of prediction results by four out of five target prediction tools, including TargetScan, PicTar, miRanda, DIANA-microT and miRDB (combining machine-learning, alignment, interaction energy and statistical tests in order to minimize false positives), (2) evidence from previous microarray analysis on the expression of these targets, (3) gene ontology (GO) and pathway enrichment analysis of the miRNA targets and their pathways and (4) linking these results to oncogenesis and cancer hallmarks. This yielded new insights into the roles of miRNAs in cancer hallmarks. Here we presented several key targets and hundreds of new targets that are significantly enriched in many new cancer-related hallmarks. In addition, we also revealed some known and new oncogenic pathways for liver cancer. These included the famous MAPK, TGFβ and cell cycle pathways. New insights were also provided into Wnt signaling, prostate cancer, axon guidance and oocyte meiosis pathways. These signaling and developmental pathways crosstalk to regulate stem cell transformation and implicate a role of miRNAs in hepatic stem cell deregulation and cancer development. By analyzing their complete interactome, we proposed new categorization for some of these miRNAs as either tumor-suppressors or oncomiRs with dual roles. Therefore some of these miRNAs may be addressed as therapeutic targets or used as therapeutic agents. Such dual roles thus expand the view of miRNAs as active maintainers of cellular homeostasis.

Previous studies focused on the association of the telomerase reverse transcriptase (TERT) gene polymorphism rs2736100 with lung cancer did not reach the same conclusion. In the present study, we performed a meta-analysis to systematically summarize the possible association between TERT polymorphism rs2736100 and the risk for lung cancer.

Glutathione S-transferase T1 (GSTT1) genetic polymorphism has been considered as a risk factor for developing malignant diseases including acute lymphoblastic leukemia; however, the results from previous studies are inconsistent. We performed a meta-analysis of 16 published studies to investigate the association between GSTT1 null variant and risk of acute lymphoblastic leukemia in childhood. Between-study heterogeneity was assessed using the I (2) statistic method. Odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CI) were pooled to assess the association. Those 16 studies were from 14 publications and included a total of 2,424 cases and 3,447 controls. Meta-analysis of a total of 16 studies showed that GSTT1 null variant was significantly associated with risk of childhood acute lymphoblastic leukemia (fixed-effect OR = 1.22, 95 %CI 1.07-1.39, P = 0.003, I (2) = 35 %). Subgroup analysis showed that GSTT1 null variant was significantly associated with risk of childhood acute lymphoblastic leukemia in Asians (fixed-effect OR = 1.47, 95 %CI 1.16-1.85, P = 0.001, I (2) = 0 %). However, there was no obvious association in both Caucasians (random-effect OR = 1.07, 95 %CI 0.83-1.38, P = 0.59, I (2) = 53 %) and Africans (random-effect OR = 0.99, 95 %CI 0.31-3.10, P = 0.98, I (2) = 72 %). Therefore, the GSTT1 null variant is significantly associated with susceptibility to childhood acute lymphoblastic leukemia in Asians.

Interleukin-23 receptor (IL23R) can interact with IL-23 and, thus, is involved in the T-helper 17 (Th17) cell-mediated inflammatory process as well as tumorigenesis. Recently, a functional single nucleotide polymorphism (SNP) rs10889677 has been identified in the 3'-untranslated region of IL-23R. It has been showed that the rs10889677AC SNP could increase the binding affinity of microRNA let-7f and downregulate IL-23R expression. Several case-control studies have examined the association between this SNP and genetic susceptibility of multiple solid tumors. However, the conclusions are conflicting. Therefore, we conducted this meta-analysis to systematically study the role of this functional IL-23R SNP in development of multiple solid tumors. There are a total of 5 studies are eligible (6731 cases and 7296 healthy controls). Either fixed-effect model or random-effect model was used to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Significant association between this functional rs10889677 genetic variant and risk of multiple solid tumors were observed (CC genotype vs. AA genotype: OR = 0.59, 95% CI = 0.53-0.66, P < 0.001). These findings demonstrated that the IL-23R rs10889677 genetic variant might play an important part during malignant transformation of multiple solid tumors.

MicroRNAs (miRNAs) are small non-coding RNA molecules, which participate in diverse biological processes and may regulate tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to diverse functional consequences, including cancer development, by altering miRNA expression. Numerous studies have shown the association between miRNA SNPs and cancer risk; however, the results are generally debatable and inconclusive, mainly due to limited statistical power. To assess the relationship between the five most common SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs2292832, and miR-27a rs895919) and the risk cancer development, we performed a meta-analysis of 66 published case-control studies. Crude odds ratios at 95% confidence intervals were used to investigate the strength of the association. No association was observed between rs2910164 and cancer risk in the overall group. However, in stratified analysis, we found that either the rs2910164 C allele or the CC genotype was protective against bladder cancer, prostate cancer, cervical cancer, and colorectal cancer, whereas it was a risk factor for papillary thyroid carcinoma and squamous cell carcinoma of the head and neck (SCCHN). Further, rs11614913 was found to be significantly associated with decreased cancer risk, in particular, for bladder cancer, gastric cancer, and SCCHN. For miR-499, a significant association was found between the rs3746444 polymorphism and cancer risk in pooled analysis. In subgroup analysis, similar results were mainly observed for breast cancer. Finally, no association was found between rs2292832 and rs895919 polymorphisms and cancer risk in the overall group and in stratified analysis. In summary, miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 are risk factors for cancer development, whereas mir-149 rs2292832 and miR-27a rs895919 are not associated with cancer risk.

Polymorphisms in X-ray cross-complementing group 3 (XRCC3) are proposed to be associated with cancer susceptibility, but previous studies on the associations between XRCC3 polymorphisms and thyroid cancer are controversial. We performed a systemic review and meta-analysis to investigate the associations of XRCC3 polymorphisms with thyroid cancer risk. We used odds ratio (OR) with 95 % confidence interval (95%CI) to assess the associations. For XRCC3 C241T polymorphism, meta-analysis of total eligible studies showed that there was no association between XRCC3 C241T polymorphism and thyroid cancer risk, but subgroup analysis in Caucasians showed that there was a significant association between XRCC3 C241T polymorphism and thyroid cancer risk (T versus C: OR = 1.30, 95%CI 1.05-1.62, P = 0.01; TT versus CC: OR = 1.74, 95%CI 1.13-2.70, P = 0.01; TT versus

Previous studies evaluating the association between XPC Lys939Gln polymorphism and cutaneous melanoma risk reported conflicting findings. We searched PubMed and Embase databases up to May 16, 2013 to identify eligible studies on the association between XPC Lys939Gln polymorphism and cutaneous melanoma risk. Finally, a total of seven case-control studies including 3,971 cases of cutaneous melanoma and 5,873 controls were included in the meta-analysis. Statistical analysis was performed with STATA version 11.0. Odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. Overall, there was no association between XPC Lys939Gln polymorphism and cutaneous melanoma risk under all five genetic models (Gln vs. Lys: OR = 1.11, 95 % CI = 0.98-1.26, P = 0.10; GlnGln vs. LysLys: OR = 1.26, 95 % CI = 0.98-1.61, P = 0.07; LysGln vs. LysLys: OR = 1.04, 95 % CI = 0.88-1.22, P = 0.64; GlnGln/LysGln vs. LysLys: OR = 1.10, 95 % CI = 0.92-1.31, P = 0.29; GlnGln vs. LysLys/LysGln: OR = 1.19, 95 % CI = 0.99-1.43, P = 0.06). Subgroup analysis in Caucasians showed that there was an obvious association between XPC Lys939Gln polymorphism and cutaneous melanoma risk in Caucasians (GlnGln vs. LysLys/LysGln: OR = 1.12, 95 % CI = 1.00-1.25, P = 0.05). Sensitivity analysis by omitting one study in turns showed that the significance of the pooled ORs was not stable. In addition, there was some evidence of publication bias in the meta-analysis, and meta-analyses of the studies with large sample size did not find the obvious association between XPC Lys939Gln polymorphism and cutaneous melanoma risk in Caucasians. Therefore, there is little evidence for the association between XPC Lys939Gln polymorphism and cutaneous melanoma risk.

Many studies were performed to assess the association between IL-4 -590C > T polymorphism and non-Hodgkin's lymphoma (NHL) risk, but no consensus was available up to now. We conducted a meta-analysis to examine the association between IL-4 -590C > T polymorphism and NHL risk. We used odds ratios (ORs) to assess the strength of the association and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. A total of six studies were found to be eligible for meta-analyses of IL-4 -590C > T variant. Results from this study showed that IL-4 -590C > T polymorphism was not significantly associated with NHL risk under all genetic models in overall population. Further sensitivity analysis confirmed the results. In subgroup analyses stratified by race, no significant association was found in either Caucasian or mixed populations. The meta-analysis indicated that elected -590C > T polymorphism of IL-4 may not be a risk factor for NHL development.

The previous published data on the association between TP53 codon 72, intron 6, and intron 3 16 bp polymorphisms and lung cancer risk remained controversial. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. 38 publications with 51 studies were selected for this meta-analysis, including 17,337 cases and 16,127 controls for TP53 codon 72 (from 43 studies), 2,201 cases and 2,399 controls for TP53 intron 6 (from four studies), and 4,322 cases and 4,558 controls for TP53 intron 3 16 bp (from four studies). When all the eligible studies were pooled into the meta-analysis of codon 72 polymorphism, there was significant association between lung cancer risk and codon 72 polymorphism in any genetic model (dominant model: OR = 1.13, 95 % CI 1.05-1.21; recessive model: OR = 1.14, 95 % CI 1.02-1.27; additive model: OR = 1.19, 95 % CI 1.05-1.33). In the subgroup analysis by ethnicity, histological type, source of control, and smoking status, significantly increased risks were observed in subgroups such as Asians, Caucasians, lung squamous cell carcinoma patients for Asians, population-based study, hospital-based study, non-smokers, and smokers. When all the eligible studies were pooled into the meta-analysis of intron 6 polymorphism, there was significant association between lung cancer risk and intron 6 polymorphism in dominant model (OR = 1.27, 95 % CI 1.11-1.44). When all the eligible studies were pooled into the meta-analysis of intron 3 16 bp polymorphism, there was significant association between lung cancer risk and intron 3 16 bp polymorphism in dominant model (OR = 1.12, 95 % CI 1.02-1.23) and additive model (OR = 1.41, 95 % CI 1.04-1.90). Additionally, when one study was deleted in the sensitive analysis, the results of TP53 intron 3 16 bp duplication polymorphism were changed in the dominant model (OR = 1.11, 95 % CI 0.87-1.42) and additive model (OR = 1.01, 95 % CI 0.65-1.56). In summary, this meta-analysis indicates that codon 72 and intron 6 polymorphisms show an increased lung cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on TP53 codon 72, intron 6, and intron 3 16 bp polymorphisms and lung cancer risk.

The XRCC1 Arg194Trp and Arg280His polymorphisms were likely to be involved with the development of bladder cancer. However, there had been inconsistent reports of association. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, and Web of Science for relevant articles with a time limit of April 25, 2013. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association between the two polymorphisms and bladder cancer susceptibility using a random-effects model. This meta-analysis including 14 case-control studies evaluated the associations between the two XRCC1 polymorphisms and bladder cancer susceptibility. Overall, for Arg194Trp, significant associations were found in TT versus CC (OR=1.78, 95% CI=1.12-2.82) and the recessive model (OR=1.71, 95% CI=1.11-2.65); for Arg280His, significant associations were also found in AG versus GG (OR=1.63, 95% CI=1.24-2.13) and the dominant model (OR=1.39, 95% CI=1.07-1.82). When stratified by ethnicity, in Asian population, significant associations were found for Arg194Trp polymorphism in TT versus CC (OR=2.99, 95% CI=1.48-6.06), the dominant model (OR=1.33, 95% CI=1.03-1.72) and the recessive model (OR=2.72, 95% CI=1.36-5.45), and for Arg280His in GA versus GG (OR=2.13, 95% CI=1.63-2.97), but no significant associations were found in no-Asian population. This meta-analysis suggested that XRCC1 Arg194Trp and Arg280His polymorphisms were risk factors for increasing bladder cancer in Asian population.

Studies on the association between the TCF7L2 rs12255372 polymorphism and breast cancer risk have reported conflicting results. To characterize the relationship between this polymorphism and breast cancer risk, we conducted a comprehensive literature search for relevant studies and performed a meta-analysis. A total of four studies including 5280 cases and 6026 controls were eligible for our analysis. Overall, we did find that this polymorphism correlates with breast cancer risk [TT versus GG: odds ratio (OR)=1.19, 95% confidence interval (CI)=1.02-1.40; GT versus GG: OR=1.10, 95% CI=1.01-1.19; T versus G: OR=1.12, 95% CI=1.05-1.19]. Furthermore, in the subgroup analysis by ethnicity, we did also find that this polymorphism associated with an increased breast cancer risk in white individuals (T versus G: OR=1.11, 95% CI=1.04-1.18). In summary, this meta-analysis suggests that the rs12255372 T allele is a low-penetrant risk factor for breast carcinogenesis. In the future, larger-scale and more well-designed studies based on homogeneous breast cancer patients are needed to validate our findings, especially in Asians.