DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility.

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.

Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals.

Background: Soluble mesothelin-related peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hinder its usefulness in surveillance programmes. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of the () gene could affect the levels of SMRP.

Objectives: To focus on SNPs located within promoter as possible critical genetic variables in determining SMRP levels.

Topoisomerase 1 Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients.

Objective: Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients.

Methods: With the use of specific software (PROMO 3.

Targeting hypoxic response for cancer therapy.

Hypoxic tumor microenvironment (HTM) is considered to promote metabolic changes, oncogene activation and epithelial mesenchymal transition, and resistance to chemo- and radio-therapy, all of which are hallmarks of aggressive tumor behavior. Cancer cells within the HTM acquire phenotypic properties that allow them to overcome the lack of energy and nutrients supply within this niche. These phenotypic properties include activation of genes regulating glycolysis, glucose transport, acidosis regulators, angiogenesis, all of which are orchestrated through the activation of the transcription factor, HIF1A, which is an independent marker of poor prognosis.

Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer.

Background: The enhancer of zeste-homolog 2 (EZH2) is involved in cancer development through gene silencing by trimethylation of lysine 27 of histone 3 (H3K27me3). The C/C genotype for the EZH2 rs3757441 single-nucleotide polymorphism (SNP) is linked with poor prognosis in metastatic colorectal cancer (CRC), but molecular and pathological characterization of this SNP is lacking.

Methods: 119 primary CRCs were analyzed.

Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk.

A genome-wide association study (GWAS) performed on a high-incidence Italian population followed by replications on low-incidence cohorts suggested a strong association of differentiated thyroid cancer (DTC) with single nucleotide polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.

Novel genome-wide association study-based candidate loci for differentiated thyroid cancer risk.

Context: Genome-wide association studies (GWASs) on differentiated thyroid cancer (DTC) have identified robust associations with single nucleotide polymorphisms (SNPs) at 9q22.33 (FOXE1), 14q13.3 (NKX2-1), and 2q35 (DIRC3).

A polymorphism in the promoter is associated with EZH2 expression but not with outcome in advanced pancreatic cancer patients.

Aim: EZH2 expression is a prognostic marker in radically resected pancreatic ductal adenocarcinoma (PDAC) patients. Here we investigated its role in locally advanced/metastatic patients, as well as candidate polymorphisms.

Materials & Methods: EZH2 expression and polymorphisms were evaluated by quantitative reverse transcription PCR in 32 laser microdissected tumors, while polymorphisms were also studied in blood samples from two additional cohorts treated with gemcitabine monotherapy (n = 93) or polychemotherapeutic regimens (n = 247).

A single nucleotide polymorphism in EZH2 predicts overall survival rate in patients with cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a deadly disease arising from the malignant transformation of cholangiocytes. Enhancer of zeste homolog 2 (EZH2) is overexpressed in poorly differentiated CCA. Functional single nucleotide polymorphisms (SNPs) in this gene may affect the role of EZH2 in cholangiocarcinogenesis and chemoresistance.

Histone lysine demethylases in breast cancer.

Histone lysine demethylases (KDMs) have been recently discovered in mammals and have been nicknamed "erasers" for their ability to remove methyl groups from histone substrates. In cancer cells, KDMs can activate or repress gene transcription, behaving as oncogenes or tumor suppressors depending upon the cellular context. In order to investigate the potential role of KDMs in Breast Cancer (BC), we queried the Oncomine database and determined that the expression of KDMs correlates with BC prognosis.

Molecular mechanisms involved in the synergistic interaction of the EZH2 inhibitor 3-deazaneplanocin A with gemcitabine in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by overexpression of enhancer of Zeste homolog-2 (EZH2), which plays a pivotal role in cancer stem cell (CSC) self-renewal through methylation of histone H3 lysine-27 (H3K27me3). Against this background, EZH2 was identified as an attractive target, and we investigated the interaction of the EZH2 inhibitor DZNeP with gemcitabine. EZH2 expression was detected by quantitative PCR in 15 PDAC cells, including seven primary cell cultures, showing that expression values correlated with their originator tumors (Spearman R(2) = 0.

An aromatase polymorphism (g.132810C>T) predicts risk of bisphosphonate-related osteonecrosis of the jaw.

Background: Bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) is an unpredictable, debilitating adverse effect. Recently, genetic polymorphisms have arisen as promising tools to identify patients with a higher risk of drug-related adverse events.

Aim: We aimed to examine the association between the aromatase polymorphism g.

Polycomb genes and cancer: time for clinical application?

Polycomb group genes (PcGs) are epigenetic effectors, essential for stem cell self-renewal and pluripotency. Two main Polycomb repressive complexes (PRC1, PRC2) mediate gene silencing through histone post-translational modifications. PcGs have been the focus of investigation in cancer research.

Epigenetics and chemoresistance in colorectal cancer: an opportunity for treatment tailoring and novel therapeutic strategies.

Colorectal cancer is the second leading cause of cancer-related deaths in the world. Despite many therapeutic opportunities, prognosis remains dismal for patients with metastatic disease, and a significant portion of early-stage patients develop recurrence after chemotherapy. Epigenetic gene regulation is a major mechanism of cancer initiation and progression, through the inactivation of several tumor suppressor genes.