The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) risk was inconsistent and underpowered. To clarify the effects of MTHFR gene polymorphisms on the risk of HCC, a meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of HCC was conducted.

Increased risk of pancreatic cancer has been reported in breast cancer families carrying BRCA1and BRCA2 mutations; however, pancreatic cancer risk in mutation-negative (BRCAX) families has not been explored to date. The aim of this study was to estimate pancreatic cancer risk in high-risk breast cancer families according to the BRCA mutation status.

Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH). Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent.

MDM2 is a major negative regulator of p53, and a single nucleotide polymorphism (SNP) in the MDM2 promoter region SNP309 has been demonstrated to be associated with an increased MDM2 expression and a significantly earlier age of onset of several tumors, including gastric cancer. Several studies were published to evaluate the association between SNP309 and gastric cancer risk. However, the results remain conflicting rather than conclusive.

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development.

The epidermal growth factor receptor (EGFR) gene copy number (GCN) has been previously demonstrated to correlate with the clinical outcome of colorectal cancer (CRC) treated with anti-EGFR monoclonal antibodies (mAbs), although it remains controversial. We conducted a systematic review and meta-analysis to assess EGFR GCN as a potential biomarker of survival for patients with advanced CRC receiving treatment with anti-EGFR mAbs.

Due to the possible involvement of Glutathione S-transferase Mu-1 (GSTM1) and Glutathione S-transferase theta-1 (GSTT1) in the detoxification of environmental carcinogens, environmental toxins, and oxidative stress products, genetic polymorphisms of these two genes may play important roles in the susceptibility of human being to hepatocellular carcinoma. However, the existing research results are not conclusive.

Emerging evidence has shown that microRNAs (miRNAs) participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP) located in the miRNAs may influence the function of mature miRNAs and then affect the processing of carcinogenesis. It has been suggested that two common SNPs rs2910164 in miR-146a and rs3746444 in miR-499 are associated with susceptibility to hepatocellular carcinoma (HCC). However, published results are inconsistent and inconclusive. To acquire a more precise effect of the association between these polymorphisms and HCC risk, we performed this meta-analysis.

The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results.

GSTP1, which is one major group of the glutathione S-transferase family, plays an important role in the metabolism of carcinogens and toxins, reducing damage of DNA as a suppressor of carcinogenesis. The 341C>T polymorphism of the GSTP1 has been implicated in cancer risk through cutting down its metabolic detoxification activities. However, results from previous studies remain conflicting rather than conclusive. To clarify the correlation and provide more statistical evidence for detecting the significance of 341C>T, a meta-analysis was conducted.

The 677C>T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene is considered to have a significant effect on colorectal cancer susceptibility, but the results are inconsistent. In order to investigate the association between the MTHFR 677C>T polymorphism and the risk of colorectal cancer, a meta-analysis was held based on 71 published studies.

PIK3CA mutation appears to predict a lack of response to anti-EGFR monoclonal antibody (mAb) treatment in patients with metastatic colorectal cancer (mCRC). However, the predictive value of PIK3CA mutations for survival remains inconclusive. Here, we pooled the data from published studies to estimate the association between PIK3CA mutation and survival outcomes in mCRC patients treated with anti-EGFR mAbs.

To assess the association between MTHFR polymorphism and cervical cancer risk, a meta-analysis was performed.

Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values <6 × 10(-6) for effect modification of current MHT use. The most significant interaction was observed for rs6707272 (P = 3 × 10(-7)) on chromosome 2 but was not replicated in the BCAC studies (P = 0.21). The potentially modifying SNPs are in strong linkage disequilibrium with SNPs in TRIP12 and DNER on chromosome 2 and SETBP1 on chromosome 18, previously linked to carcinogenesis. However, none of the interaction effects reached genome-wide significance. The inability to replicate the top SNP × MHT interaction may be due to limited power of the replication phase. Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women.

We have performed a meta-analysis of cancer risk associated with the rs17878362 polymorphism of the TP53 suppressor gene (PIN3, (polymorphism in intron 3), 16 bp sequence insertion/duplication in intron 3), using a compilation of a total of 25 published studies with 10 786 cases and 11 760 controls. Homozygote carriers of the duplicated allele (A2A2) had a significantly increased cancer risk compared with A1A1 carriers (aggregated odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.22-1.74). However, there was no significant effect for the A1A2 heterozygotes (A1A2 versus A1A1 aggregated OR = 1.08, 95% CI = 0.99-1.18). No significant heterogeneity or publication bias was detected in the data set analysed. When comparing populations groups, increased cancer risk was associated with A2A2 carriage in Indian, Mediterranean and Northern Europe populations but not in the Caucasian population of the United States. Analysis by cancer site showed an increased risk for A2A2 carriers for breast and colorectal, but not for lung cancers. These results support that the A2A2 genotype of rs17878362 is associated with increased cancer risk, with population and tumour-specific effects.

Budd-Chiari syndrome (BCS) can be incidentally complicated by hepatocellular carcinoma (HCC), thereby decreasing the survival of these patients. Our study aims to systematically review the prevalence and risk factors of HCC in BCS patients.

CD133 has recently been reported as a marker of cancer stem-like cells in colorectal cancer (CRC). However, its predictive value in CRC still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and clinicopathological features and the outcome of CRC patients by performing a meta-analysis.

Renal cell adenocarcinoma requires different therapeutic pathways because it is one of the most therapy-resistant tumors, on the other hand it is biologically one of the most attractive tumors. Its pathological classification has a genetic base. There is an anomaly of the Von Hippel Lindau gene in 80% of adenocarcinomas, being this fact determinant to know the biological characteristics of tumor initiation and development, as well as the identification of factors susceptible to be used as therapeutic targets. Since 2005 a group of molecules have been used in the treatment of metastatic adenocarcinomas and, even though therapeutic results are significant but not clinically relevant yet, we are sure they are a key way for more efficient future developments. The present study tries to make a tour on the research of the biological anomalies in renal adenocarcinoma with special emphasis in the Von HippelLindau gene.

Emerging evidence showed that common functional -31G>C polymorphism (rs9904341 G>C) in the promoter region of the survivin gene is involved in the regulation of survivin expression, thus increasing an individual's susceptibility to gastrointestinal tract (GIT) cancer; but individually published results are inconclusive. The aim of this systematic review and meta-analysis was to derive a more precise estimation of the association between survivin -31G>C polymorphism and GIT cancer risk.