Esophageal cancer affects more than 4,50,000 persons worldwide, and its incidence has increased in recent years. It is the eighth most common cancer across the globe. The main histologic types are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA), and their associated risk factors are well known. Achalasia, an idiopathic esophageal disorder that conditions aperistalsis and the absence of lower esophageal sphincter relaxation, stands out among them. The prevalence of ESCC in subjects with esophageal achalasia is 26 in every 1,000 cases, whereas the prevalence of EA is 4 in every 1,000. Patients with achalasia have a 50 times higher risk of presenting with ESCC than the general population, and the disease manifests 20-25 years after achalasia symptom onset. Multiple mechanisms are related to the development of ESCC in achalasia, and they include bacterial overgrowth, food stasis, genetic alterations, and chronic inflammation. Regarding the risk of EA in achalasia patients, most cases are associated with Barrett's esophagus, due to uncontrolled chronic acid reflux. Given that achalasia is a well-established factor for ESCC/EA, clinicians must be aware of said associations to enable the development of programs for the prevention and opportune detection of these cancers in patients with achalasia.

Whether cyclin D1 (CCND1) gene variants increase susceptibility to head and neck cancer (HNC) is undetermined. Therefore, we performed the present meta-analysis to systematically assess any possible association between CCND1 variants (G870A and G1722C) and HNC risk. Seventeen studies for CCND1 G870A and three studies for CCND1 G1722C were included. Overall, CCND1 polymorphisms (G870A and G1722C) had no association with increased HNC risk (p>0.05). In the subgroup analysis by smoking status, significantly increased HNC risk was found among smokers under allele contrast, homozygous comparison and recessive models (p<0.05), smoking carriers of A allele and AA genotype appearing at elevated risk. In conclusion, while there was overall a lack of any association between CCND1 polymorphisms (G870A and G1722C) and HNC risk, smokers carrying the A allele and AA genotype of the CCND1 G870A polymorphism may be susceptible to HNC development.

Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer by incidence worldwide. Although the cancer is located at a readily recognizable and accessible site in the body, it is the sixth most common cause of cancer death. The 1- and 5-year survival rates in China are 50% and 15%, respectively. Furthermore, the cancer has distinct geographic and etiological risk factors in different locations around the world. Since ESCC is highly prevalent in the Chaoshan (Southeastern) region of China, this report will focus on a review of risk factors for the cancer in this area. From the review, it is clear that some important and traditional factors are involved, e.g. environmental mutagens, genetic predisposition. However, unique factors, e.g. the drinking of very hot tea, may play an important role. This review highlights the role of complex risk factors (environmental, genetic and cultural) which contribute to the multistage development of cancer: localized injury, inflammation, mitogenesis, mutagenesis, carcinogenesis and eventually mortality. The latter is contributed by unnecessary delay in seeking medical care which may be culturally related. The review emphasizes the need to identify causal mechanisms for the complex carcinogenic process which can provide opportunity for prevention and treatment of this potentially curable cancer.

Cylin D1(CCDN1) is an important regulator of the cell cycle whose alterations are thought to be involved in cancer development. There have been many studies indicating CCDN1 amplification or over- expression in a variety of cancer types. In addition to gene amplification, the G870A polymorphism may be related with altered CCDN1 activity, and therefore with cancer development. This hypothesis has been tested in different cancer types but results have been contradictory. We therefore aimed to investigate any relationship between CCDN1 A870G genotypes and laryngeal squamous cell cancer development and progression.

A total of 68 Turkish patients with primary laryngeal squamous cell cancer and 133 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the CCDN1 genotypes.

No significant association was detected between CCDN1 genotypes and laryngeal squamous cell cancer (LxSCCa) development. Similarly CCDN1 genotypes were not related to clinical parameters of Lx SCCa. However, there was a very significant association between CCDN1 G allele and presence of perineural invasion (p= 0.003; OR: 1.464; CI% 1.073-1.999). CCDN1 G allele frequency was significantly higher in the individuals with perineural invasion (85.7%) when compared to those without (58.5%). The 2 patients who died of disease were both found to possess the GG genotype.

These results pose a controversy in suggesting a protective role of the G allele against LxSCCa development and support the association of CCDN1 gene GG genotype with mortality in patients with LxSCCa.

The common functional cyclin D1 (CCND1) G870A polymorphism may influence the risk of esophageal cancer. However, the conclusions of previous studies have been inconsistent for the association between the CCND1 G870A polymorphism and esophageal cancer risk. A meta-analysis of 11 published case-control studies was performed, including 2,111 patients with esophageal cancer and 3,232 controls, to investigate the association between the CCND1 G870A polymorphism and esophageal cancer risk. The odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between the CCND1 G870A polymorphism and esophageal cancer risk. A significant association between the CCND1 G870A polymorphism and esophageal cancer risk was observed for the allele contrast (A vs. G: OR, 1.23; 95% CI, 1.02-1.48; P=0.029), codominant (AA vs. GG: OR, 1.58; 95% CI; 1.06-2.35; P=0.024) and recessive models (AA vs. GG + GA: OR, 1.33, 95% CI, 1.03-1.73; P=0.030). However, in the stratified analysis by ethnicity, study design and pathology, there was no significant association detected in these genetic models. In conclusion, results of the meta-analysis suggested that the CCND1 G870A polymorphism is a potential risk factor in the development of esophageal cancer.

Alterations of cyclin D1, one of the main regulators of the cell cycle, are known to be involved in various cancers. The CCDN1 G870A polymorphism causes production of a truncated variant with a shorter half-life and thus thought to impact the regulatory effect of CCDN1. The aim of the present study was to contribute to existing results to help to determine the prognostic value of this specific gene variant and evaluate the role of CCDN1 G870A polymorphism in brain cancer susceptibility. A Turkish study group including 99 patients with primary brain tumors and 155 healthy controls were examined. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The CCDN1 genotype frequencies in meningioma, glioma and control cases were not significantly different (p>0.05). No significant association was detected according to clinical parameters or tumor characteristics; however, a higher frequency of AG genotype was recorded within patients with astrocytic or oligoastrocytic tumors. A significant association between AG genotype and gliobilastoma multiforme (GBM) was recorded within the patients with glial tumors (p value=0.048 OR: 1.87 CI% 1.010-3.463). According to tumor characteristics, no statistically significant difference was detected within astrocytic, oligoasltrocytic tumors and oligodentrioglias. However, patients with astrocytic astrocytic or oligoastrocytic tumors showed a higher frequency of AG genotype (50%) when compared to those with oligodendrioglial tumors (27.3%). Our results indicate a possible relation between GBM formation and CCDN1 genotype.

Esophageal cancer (EsC) is one of the least studied and deadliest cancers worldwide because of its extremely aggressive nature and poor survival rate. It ranks sixth among all cancers in mortality. In retrospective studies of EsC, smoking, hot tea drinking, red meat consumption, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barrett's esophagus is clearly recognized as a risk factor for EsC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we investigated the epidemiologic patterns and causes of EsC. Using population based cancer data from the Surveillance, Epidemiology and End Results Program of the United States; we generated the most up-to-date stage distribution and 5-year relative survival by stage at diagnosis for 1998-2009. Special note should be given to the fact that esophageal cancer, mainly adenocarcinoma, is one of the very few cancers that is contributing to increasing death rates (20%) among males in the United States. To further explore the mechanism of development of EsC will hopefully decrease the incidence of EsC and improve outcomes.

PAK5 (p21 activated kinase 5) is upregulated in human colorectal carcinoma cells and is a known tumor promoter in carcinogenesis of the colon. Little is known regarding the mechanisms underlying the downstream targets of PAK5, and information concerning its biological significance in glioma is lacking. In this study, we investigated the effects of PAK5 on proliferation, migration, invasion, and apoptosis in human U87 and U251 glioma cells and examined the underlying molecular mechanism. We performed cell growth assays and cell cycle analysis to observe the cell proliferation. Flow cytometry analysis was performed to evaluate apoptosis, and in vitro scratch assays, cell migration assays, and gelatin zymography were performed to examine cell migration. Western blot analysis was performed to examine signal transduction in the cells. We demonstrated that suppression of PAK5 in glioma cells significantly inhibited cell migration and invasion. We also observed that suppression of PAK5 in human glioma cell lines inhibited cell growth because of G1 phase arrest. Additionally, flow cytometry and Western blot analysis indicated that PAK5 could inhibit cell apoptosis. These results suggest that the PAK5-Egr1-MMP2 signaling pathway is involved in tumor progression and may have a potential role in cancer prevention and treatment.

p21-activated kinases (PAKs) are activated by various extracellular stimuli and, in turn, activate other kinases by phosphorylating them at specific serine/threonine residues or through protein-protein interaction. As a recently identified member of the group B PAK family, the role of PAK5 in cancer is poorly understood. In this study, we investigated the effect of PAK5 on the malignant phenotype, such as proliferation, cell cycle, apoptosis, migration, and invasion. Cell growth assay and cell cycle analysis consistently showed that knockdown of PAK5 could significantly inhibit the proliferation of breast cancer cells. Wound healing assay. migration assay, and invasion assay showed that PAK5 promoted cell migration. Furthermore, in order to elucidate the underlying mechanism of PAK5 on cellular growth and migration, we examined the protein expressions of cyclin D1, p21, early growth response protein 1 (Egr1), and matrix metalloproteinase 2 (MMP2). Our work further reveals the PAK5-Egr1-MMP2 signaling pathway to be a critical regulator of cell migration and invasion. These results suggest that PAK5 may be a potential therapeutic target for breast cancer.