To perform a meta-analysis investigating the association of MTHFR C677T polymorphism and susceptibility of cervical cancer. All case-control studies published in English and Chinese with estimates of the relationship between MTHFR C677T polymorphism and risk of cervical cancer were analyzed using odds ratio (OR) with 95 % confidence interval (CI). A total of 10 studies (2,023 cases and 2,570 controls) were included in the meta-analysis. No significant association was observed between T allele and C allele (OR = 0.90; 95 %CI = 0.70-1.17; P = 0.43), and for genotype TT versus CC (OR = 1.09; 95 %CI = 0.74-1.61; P = 0.67), CT versus CC (OR = 0.95; 95 %CI = 0.75-1.20; P = 0.65), CT + TT versus CC (OR = 0.91; 95 %CI = 0.66-1.24; P = 0.55). The current meta-analysis results suggest that the MTHFR C677T polymorphism may not be associated with cervical cancer.

Cervical cancer develops through progression from normal cervical epithelium through squamous intraepithelial lesions (SIL) to invasive cancer. Cervical cancer is associated with oncogenic human papillomavirus (HPV). The HPV E6 oncoprotein binds to the tumor suppressor gene product p53, promoting its degradation; the Arg allele of p53 Arg72Pro polymorphism binds more ardently with HPV E6 than the Pro variant. Here we evaluate the role of p53 Arg72Pro polymorphism and HPV status on the initiation, progression, and development of cervical cancer. A systematic review and meta-analysis were conducted. Events of interest were the initiation of neoplasia (SIL vs. normal), progression to invasive cancer (cervical cancer vs. SIL), and risk of invasive cancer (cervical cancer vs. normal) by HPV status. OR were extracted from individual studies and pooled using generic inverse variance and random effects modeling. Forty-nine studies were included. In individuals showing HPV positivity, there was a significantly higher odds of progression from SIL to cervical cancer with the p53 Arg allele [OR 1.37; 95% confidence intervals (CI), 1.15-1.62; P < 0.001]. This association was not seen in HPV-negative individuals. p53 Arg72Pro was not associated with the risk of cervical cancer or initiation of SIL in either HPV-positive or HPV-negative patient subsets. The Arg variant of p53 Arg72Pro is associated with progression of SIL to cervical cancer only in the presence of HPV positivity. There were no associations of this variant with overall risk or initiation of cancer in either HPV-positive or HPV-negative patients. Clin Cancer Res; 18(23); 6407-15.

There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer.

Mutation of BRAF is a predominant event in cancers with poor prognosis such as melanoma and colorectal cancer. BRAF mutation leads to a constitutive activation of mitogen activated protein kinase pathway which is essential for cell proliferation and tumor progression. Despite tremendous efforts made to target BRAF for cancer treatment, the correlation between BRAF mutation and patient survival is still a matter of controversy.

Recently, many studies have been published to evaluate the correlation between the cytochrome P450 1A1 (CYP1A1) T3801C polymorphism and cervical neoplasia risk. However, the results remain inconclusive. To clarify this possible association, we conducted a systematic review and meta-analysis of published studies. Data were collected from the following electronic databases: PubMed, Embase, Ovid, ISI Web of Knowledge, Google Scholar, and Chinese Biomedical Database databases. The pooled odds ratio (OR) and its 95 % confidence interval (95 % CI) were used to assess the strength of this association. The pooled ORs were performed for the allele model (C vs. T), the homozygote model (CC vs. TT), the dominant model (CC/CT vs. TT), and the recessive model (CC vs. TT/CT), respectively. Finally, a total of 12 independent studies including a total of 3,724 subjects (1,912 cases/1,812 controls) were eligible for meta-analysis. Overall, there was a significant association between the CYP1A1 T3801C polymorphism and cervical neoplasia susceptibility (C vs. T, OR 1.32, 95 % CI 1.04-1.68, P = 0.02; CC vs. TT, OR 1.99, 95 % CI 1.19-3.35, P = 0.01; CC/CT vs. TT, OR 1.36, 95 % CI 1.02-1.81, P = 0.02; CC vs. TT/CT, OR 1.57, 95 % CI 1.23-2.02, P < 0.01). Meta-analysis of the ten studies on cervical cancer suggested a significant association between the CYP1A1 T3801C polymorphism and cervical cancer risk (C vs. T, OR 1.38, 95 % CI 1.05-1.82, P = 0.02; CC vs. TT, OR 2.06, 95 % CI 1.15-3.70, P = 0.02; CC/CT vs. TT, OR 1.45, 95 % CI 1.03-2.02, P = 0.03; CC vs. TT/CT, OR 1.56, 95 % CI 1.20-2.03, P < 0.01). In the stratified analysis by ethnicity, significant associations were also detected in some genetic models. This meta-analysis demonstrates a significant association between the CYP1A1 T3801C polymorphism and cervical neoplasia susceptibility.

Glioblastoma multiforme (GBM) is an incurable form of brain cancer with a very poor prognosis. Because of its highly invasive nature, it is impossible to remove all tumor cells during surgical resection, making relapse inevitable. Further research into the regulatory mechanism underpinning GBM pathogenesis is therefore warranted, and over the past decade, there has been an increased focus on the functional role of microRNA (miRNA). This systematic review aims to present a comprehensive overview of all the available literature on the expression profiles and function of miRNA in GBM. Here, we have reviewed 163 papers and identified 253 upregulated, 95 downregulated, and 17 disputed miRNAs with respect to expression levels; 85 % of these miRNAs have not yet been functionally characterized. A focus in this study has been 26 interesting miRNAs involved in the mesenchymal mode of migration and invasion, demonstrating the importance of miRNAs in the context of the cellular niche. Both oncogenic and tumor-suppressive miRNAs were found to affect target genes involved in cell migration, cytoskeletal rearrangement, invasiveness, and angiogenesis. Clearly, the distinct functional properties of these miRNAs need further investigation and might hold a great potential in future molecular therapies targeting GBM.

The use of lymphatic microvessel density (LVD) and pro-lymphangiogenic mediators as prognostic factors for survival in breast cancer remains controversial. We searched the electronic databases PubMed and EMBASE without language restrictions for relevant literature to aggregate the survival results. To be eligible, every study had to include the assessment of the LVD or the expression of vascular endothelial growth factor (VEGF)-C or -D in patients with breast cancer and provide a survival comparison, including disease-free survival (DFS) or overall survival (OS), according to the LVD, VEGF-C or VEGF-D status. Across all studies, 56.64 % of patients were considered to have a VEGF-C-positive tumor, and 65.54 % of patients had VEGF-D-positive tumors. High LVD had an unfavorable impact on DFS, with a pooled hazard ratio (HR) of 2.222 (95 % CI 1.579-3.126) and an OS with a HR of 2.493 (95 % CI 1.183-5.25). According to the different lymphatic makers, the subgroup HR in the D2-40 studies was 2.431 (95 % CI 1.622-3.644) for DFS and 4.085 (95 % CI 1.896-8.799) for OS. VEGF-C overexpression, as assessed by immunochemistry, was a prognostic factor for decreased DFS (HR 2.164; 95 % CI 1.256-3.729) and for decreased OS (HR 2.613; 95 % CI 1.637-4.170). VEGF-D overexpression was a significant although weak prognostic factor for DFS only when assessed by immunochemistry, with a HR of 2.108 (95 % CI 1.014-4.384). Our meta-analysis demonstrated that LVD, VEGF-C and VEGF-D could predict poor prognosis in patients with breast cancer. However, standardization of the assessment of LVD and for the expression of lymphangiogenesis factors is needed.

Evidence is accumulating that cyclooxygenase-2 (COX-2) may play an important role in prostate cancer (PCa). Recently, gene polymorphisms in COX-2 have been implicated to alter the risk of PCa and overexpression of COX-2 may be associated with clinical and prognostic significance in PCa. However, the results of these studies are inconclusive or controversial. To derive a more precise estimation of the relationships, we performed an updated meta-analysis. A comprehensive search was conducted to examine all the eligible studies of COX-2 polymorphism and expression in PCa. We used odds ratios (ORs) to assess the strength of the association and the 95 % confidence intervals (CIs) give a sense of the precision of the estimate. Overall, no significant associations between COX-2 polymorphism and PCa risk were found. However, high expression of COX-2 was significantly higher in T3-T4 stages of PCa than in T1-T2 stages of PCa (OR = 2.33, 95 %CI: 1.54-3.53, P < 0.0001). COX-2 might play an important role in the progress of PCa, overexpression of COX-2 correlates with T3-T4 stages of PCa. COX-2 might be a potential therapy target for PCa and work as a prognostic factor for PCa patients.

Potential xeroderma pigmentosum group D (XPD), also called excision repair cross-complimentary group two (ERCC2), Lys751Gln and Asp312Asn polymorphisms have been implicated in gastric cancer risk among different ethnicities.

Genetic variation in DNA repair genes can modulate DNA repair capacity and may be related to cancer risk. However, study findings have been inconsistent. Inheritance of variant DNA repair genes is believed to influence individual susceptibility to the development of environmental cancer. Reliable knowledge on which the base excision repair (BER) sequence variants are associated with cancer risk would help elucidate the mechanism of cancer. Given that most of the previous studies had inadequate statistical power, we have conducted a systematic review on sequence variants in three important BER proteins. Here, we review published studies on the association between polymorphism in candidate BER genes and cancer risk. We focused on three key BER genes: 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease (APE1/APEX1) and x-ray repair cross-complementing group 1 (XRCC1). These specific DNA repair genes were selected because of their critical role in maintaining genome integrity and, based on previous studies, suggesting that single-nucleotide polymorphisms (SNPs) in these genes have protective or deleterious effects on cancer risk. A total of 136 articles in the December 13, 2010 MEDLINE database (National Center for Biotechnology Information, http://www.ncbi.nlm.nih.gov/pubmed/) reporting polymorphism in OGG1, XRCC1 or APE1 genes were analyzed. Many of the reported SNPs had diverse association with specific human cancers. For example, there was a positive association between the OGG1 Ser326Cys variant and gastric and lung cancer, while the XRCC1 Arg399Gln variant was associated with reduced cancer risk. Gene-environment interactions have been noted and may be important for colorectal and lung cancer risk and possibly other human cancers.

Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations.

Previous studies investigating the association between X-ray repair cross-complementation group 1(XRCC1) polymorphisms and cervical cancer (CC) risk has provided inconsistent results. The aim of our study was to assess the association between the XRCC1 gene Arg399Gln, Arg194Trp, Arg280His polymorphisms and risk of CC.

Many epidemiological studies have found that leptin correlates to body fat extent and breast cancer. Leptin exerts its physiological action through the leptin receptor (LEPR). However, published data on the association between LEPR alleles and breast cancer occurrence have led to in contradictory results. A total of 10 studies were identified to the meta-analysis, including 4,644 cases and 5,485 controls for LEPR rs1137101 polymorphism, 5 studies with 2,759 cases and 4,464 controls for rs1137100 polymorphism, and 2 studies for rs8051542, rs8051542, and rs8051542 polymorphisms. The pooled odds ratios (OR) with 95 % confidence intervals (CI) for breast cancer risk associated with LEPR genotypes were estimated. Elevated breast cancer risk was associated with LEPR rs1137101 polymorphism when all studies were pooled in the meta-analysis (allele contrast model: OR = 0.71, 95 % CI = 0.551-0.997). In the stratified analysis by ethnicity, significantly increased risks were also found among Asians for allele contrast model (OR 0.414, 95 % CI 0.312-0.550) and dominant model (OR 0.537, 95 % CI 0.370-0.781); for Africans, significantly increased risks were also found for allele contrast model (OR 0.716, 95 % CI 0.595-0.861), homozygote codominant (OR 0.537, 95 % CI 0.370-0.781) and dominant model (OR 1.595, 95 % CI 1.207-2.108). And significantly elevated breast cancer risk was associated with LEPR rs1137100 polymorphism for allele contrast (OR = 0.666, 95 % CI = 0.603-0.720) and homozygote codominant models (OR = 0.344, 95 % CI = 0.282-0.421). For LEPR rs8179183, rs4655537, and rs3762274 polymorphisms, no significant associations were detected in all comparison models. This pooled analysis suggested that rs1137101 and rs1137100 polymorphisms were significantly correlated with breast cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR rs1137100 variant were low-penetrant risk factors for developing breast cancer. Further, no significant associations existed between LEPR rs8179183, rs4655537, and rs3762274 polymorphisms and risk of breast cancer.

The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations.

Interindividual variations in radiotoxicity responses exist despite uniform treatment protocols. It is speculated that normal genetic variants, particularly single nucleotide polymorphisms (SNPs) may influence normal head and neck (HN) tissue radiotoxicity. This first-ever systematic review was undertaken to evaluate the association of SNPs with normal HN tissues radiotoxicity. Multiple databases (1950-February 2012) were reviewed using a combination of related keywords and MeSH terms. All published HN radiotoxicity studies with sufficient relevant data for extraction were included. The outcomes evaluated were acute and late radiotoxicity endpoints. Methodological quality assessment based on the STrengthening the REporting of Genetic Association (STREGA) statement was performed. Seven articles from 692 articles searched fulfilled the eligibility criteria. Recruited sample sizes were small (range, 32-140). There were 5/7 case-control studies. All studies used multimodality treatment with heterogeneous radiation parameters. Candidate gene approach was used in all studies. Fourteen SNPs from 9 genes were evaluated from the following pathways: DNA damage response, radiation fibrogenesis and oxidative/xenobiotic metabolism. Acute radiotoxicity events were associated with SNPs of DNA repair genes (OR, 3.01-4.08). SNPs of TGFβ1 were associated with osteoradionecrosis (OR, 4.2) and subcutaneous fibrosis. Genetic association studies in HN radiotoxicity currently provide hypothesis-generating findings that require validation in larger studies. Future studies must incorporate critical methodological issues and technological improvements, including using a genome-wide approach. Headway is possible through case-pooling of existing clinical trial data which could create a larger sample size of well-characterized treatment and endpoints. Also, on-going HN cancer clinical trials should consider extending their toxicity evaluation to include genetic association studies.

Clinicians have long sought to characterize biological markers of neoplasia as objective indicators of tumor presence, pathogenicity, and prognosis. Armed with data that correlate biomarker activity with disease presence and progression, clinicians can develop treatment strategies that address risks of disease recurrence or persistence and progression. The B-type Raf kinase (BRAF V600E) mutation in exon 15 of the BRAF gene has been noted to be a putative prognostic marker of the most prevalent form of thyroid cancer, papillary thyroid cancer (PTC)--a tumor type with high proclivity for recurrence or persistence. There has been a remarkable interest in determining the association of BRAF mutation with PTC recurrence or persistence. Using many new studies that have been published recently, we performed a meta-analysis to investigate correlations of BRAF mutation status with PTC prognosis, focusing on the recurrence or persistence of the disease after initial treatment. The study was based on published studies included in the PubMed and Embase databases addressing the BRAF mutation and the frequency of recurrence of PTC. We selected studies with data that enabled measurement of the risk ratio for recurrent disease. We also analyzed the factors that are classically known to be associated with recurrence. These factors included lymph node metastasis, extrathyroidal extension, distant metastasis, and American Joint Committee on Cancer (AJCC) stages III/IV. We used 14 articles that included an analysis of these factors as well as PTC recurrence data, with a total of 2470 patients from 9 different countries. The overall prevalence of the BRAF mutation was 45%. The risk ratios in BRAF mutation-positive patients were 1.93 (95% confidence interval [CI], 1.61-2.32; Z = 7.01; p < 0.00001) for PTC recurrence, 1.32 (95% CI, 1.20-1.45; Z = 5.73; p < 0.00001) for lymph node metastasis, 1.71 (95% CI, 1.50-1.94; Z = 8.09; p < 0.00001) for extrathyroidal extension, 0.95 (95% CI, 0.63-1.44; Z = 0.23; p = 0.82) for distant metastasis, and 1.70 (95% CI, 1.45-1.99; Z = 6.46; p < 0.00001) for advanced stage AJCC III/IV. Thus, in this meta-analysis, the BRAF mutation in PTC was significantly associated with PTC recurrence, lymph node metastasis, extrathyroidal extension, and advanced stage AJCC III/IV. Patients with PTC harboring mutated BRAF are likely to demonstrate factors that are associated with an increased risk for recurrence of the disease, offering new prospects for optimizing and tailoring initial treatment strategies to prevent recurrence.

Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.

Angiogenesis, the formation of new vessels from pre-existing ones, is essential during ontogenetic development and is related to many important physio-pathological processes in the adult. In fact, a persistent and deregulated angiogenesis is a required event for many diseases and pathological situations, including cancer progression and metastasis. Some rare diseases are also angiogenesis-related pathologies. However, there is a lack of an exhaustive review on the topic. The main purpose of this work is to carry out a systematic review of literature to determine what (and how much) scientific information concerning angiogenesis-related rare diseases can be extracted from available sources. After exhaustive searches in bibliographic databases, preselected data were filtered by selecting only those articles on rare diseases with an Orpha number hosted in the Orphanet web. The selected bibliographic references were further curated manually. With the 187 selected references, a critical reading and analysis was carried out allowing for an identification and classification of angiogenesis-related rare diseases, the involved genes and the drugs available for their treatment, all on the basis of the information available in Orphanet database.

We aimed to explore the role of IL-10 -592 A/C SNP in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. 17 studies were eligible for the meta-analysis. We adopted the most probably appropriate genetic model (recessive model). Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication biases were estimated. IL-10-592 AA genotype is associated with the reduced risk of developing gastric cancer among Asians and even apparently observed among Asians high quality subgroup, suggesting IL-10-592 AA genotype may seem to be more protective from overall gastric cancer in Asian populations. IL-10-592 AA genotype is also associated with the overall reduced gastric cancer susceptibility in persons with H. pylori infection compared with controls without H. pylori infection, suggesting IL-10-592 AA genotype may seem to be more protective from overall gastric cancer susceptibility in persons infected with H. pylori. IL-10-592 AA genotype is not associated with either pathologic subtypes (intestinal or diffuse) or anatomic subtypes (non-cardia or cardia) of gastric cancer susceptibility. Genotyping methods like direct sequencing should be highly advocated to be conducted in future well-designed high quality studies among different ethnicities or populations.

Relationship between the p27Kip1 (here after referred to as p27) V109G polymorphism and cancer risk has been extensively studied; however, results from different studies were not fully consistent. Therefore, we carried out a meta-analysis to comprehensively assess the correlation between the p27V109G polymorphism and the cancer risk. Articles on the relationship of the p27V109G polymorphism with cancer risk were searched from Medline, Pub Med, and Web of science databases. A total of eight eligible studies with 3591 cases and 3799 controls were included in this meta-analysis. Overall, it seemed that the G allele was not associated with the elevated cancer risk (pooled odds ratio [OR]=0.98, 95% confidence interval [CI]: 0.88-1.09, p=0.68, fixed effects). Analyses in different populations revealed that no statistically significant associations between the G allele and cancer risk were demonstrated in Caucasians or Asians. When analyzed in different types of cancer that, from two studies, the G allele was found to be associated with a decreased risk of prostate cancer in a dominant genetic model (pooled OR=0.60, 95% CI=0.36-0.98, p=0.04, fixed effects), but did not alter the breast cancer risk from four studies. In conclusion, this meta-analysis indicated that the p27V109G polymorphism did not correlate with the overall cancer risk in the general population.