Measurement of DNA damage in peripheral blood by the γ-H2AX assay as predictor of colorectal cancer risk.

The detection of γ-H2AX focus is one of the most sensitive ways to monitor DNA double-strand breaks (DSBs). Although changes in γ-H2AX activity have been studied in tumor cells in colorectal cancer (CRC), changes in peripheral blood lymphocytes (PBLs) have not been examined previously. We hypothesize that higher levels of irradiation-induced γ-H2AX in PBLs may be associated with an elevated risk of colorectal cancer (CRC).

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry.

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.

Increased leukocyte mitochondrial DNA copy number is associated with oral premalignant lesions: an epidemiology study.

Although changes in the mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) have been linked to increased susceptibility to several cancers, the relationship between the mtDNA copy number in PBLs and the risk of cancer precursors has not been investigated. In this study, we measured the relative mtDNA copy number in PBLs of 143 patients with histologically confirmed oral premalignant lesions (OPLs) and of 357 healthy controls that were frequency-matched to patients according to age, sex and race. OPL patients had a significantly higher mtDNA copy number than the controls (1.

Short telomere lengths in peripheral blood leukocytes are associated with an increased risk of oral premalignant lesion and oral squamous cell carcinoma.

Background: Oral premalignant lesions (OPLs) are precursors of oral squamous cell carcinoma (OSCC). Short telomeres in peripheral blood leukocytes (PBLs) are associated with increased risks of several cancers. However, it is unclear whether short leukocyte telomere length (LTL) predisposes individuals to OPL and OSCC.

Genetic variations in base excision repair pathway and risk of bladder cancer: a case-control study in the United States.

Base excision repair (BER) is one of the major cellular DNA repair pathways that repairs small isolated foci of DNA damage including reduced or oxidized single bases or fragments and small, non-bulky adducts. Genetic variations in BER genes may affect DNA repair capacity and increase susceptibility to bladder cancer. In a case-control study of 801 bladder cancer patients and 801 matched controls, we evaluated the associations of 167 single nucleotide polymorphisms (SNPs) from 19 genes of the BER pathway with the risk of bladder cancer.

γ-H2AX level in peripheral blood lymphocytes as a risk predictor for bladder cancer.

Identification of susceptibility to double-strand breaks (DSBs) may provide valuable information about individual bladder cancer (BC) risk. The formation of γ-H2AX foci is a highly sensitive marker for DNA DSBs induction. We assessed whether levels of γ-H2AX in peripheral blood lymphocytes (PBL) obtained after stimulation by ionizing radiation (IR) are able to predict BC risk.

Risk assessment of esophageal adenocarcinoma using γ-H2AX assay.

Background: Mutagen-induced DNA damage as measured in peripheral blood lymphocytes (PBL) has been associated with increased risks of cancers. The formation of γ-H2AX is an early cellular response to DNA double-strand breaks (DSB). We hypothesize that higher level of radiation-induced γ-H2AX in PBLs may be associated with an increased risk of esophageal adenocarcinoma.

Reduced mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of soft tissue sarcoma.

Mitochondrial DNA (mtDNA) has increased susceptibility to damage due to its close proximity to the site of reactive oxygen species production, lack of introns and protective histones, and less efficient DNA repair mechanisms than nuclear DNA. The relationship between mtDNA copy number in peripheral blood leukocytes (PBLs) and the risk of soft tissue sarcoma (STS) has not been investigated. In this study, we determined the relative mtDNA copy number in PBLs of 325 patients (cases) with histologically confirmed STS and 330 healthy controls that were frequency matched to cases according to age, sex and ethnicity.

Ionizing radiation-induced γ-H2AX activity in whole blood culture and the risk of lung cancer.

Background: Phenotypic biomarkers of DNA damage repair may enhance cancer risk prediction. The γ-H2AX formed at the sites of double-strand break (DSB) after ionizing radiation is a specific marker of DNA damage.

Methods: In an ongoing case-control study, the baseline and ionizing radiation-induced γ-H2AX levels in peripheral blood lymphocytes (PBL) from frequency-matched 306 untreated patients with lung cancer and 306 controls were measured by a laser scanning cytometer-based immunocytochemical method.

NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules.

The midbody is a structural organelle formed in late phase mitosis which is responsible for completion of cytokinesis. Although various kinds of proteins have been found to distribute or immigrate to this organelle, their functions have still not been completely worked out. In this study, we demonstrated that NAT10 (N-acetyltransferase 10, NAT10) is not only predominantly distributed in the nucleolus in interphase, but is also concentrated in the mitotic midbody during telophase.

A cluster of polypyrimidine tracts is involved in the transcription regulation of telomerase transcriptional elements-interacting factor.

In a previous study, we demonstrated that telomerase transcriptional elements-interacting factor (TEIF) could up-regulate the expression of telomerase and DNA polymerase beta, increasing resistance to genotoxic agents. Here, we further report that TEIF can be stimulated by DNA damage and we have identified a cluster of repeated polypyrimidine tracts in the promoter of TEIF, which mediate both its basal transcription and its response to genotoxic agents. These polypyrimidine tracts are arranged in three types of repeating units and in each of these units there are 14 bp length tandem sequences, which are repeated three times.

[Nucleolar localization of human acetyltransferase-like protein and its expression in tumors].

Objective: To confirm the nucleolar localization of telomerase-regulation associated protein-human N-acetyltransferase-like protein (hALP) and its associated functions.

Methods: Immunofluoresent staining and immunoelectron microscopy were used to detect the distribution of hALP in HeLa and Saos2 cells, and the co-localization of hALP and rDNA was analyzed by fluorescence in situ hybridization and immunofluoresence. RNAi was performed to further verify the nucleolar localization of hALP.

[Expression of TEIF protein in soft tissue tumors and its significance].

Objective: To evaluate the expression of TEIF protein in human tumors of soft tissue and its significance.

Methods: Anti-TEIF polyclonal antibody was generated by immunization of E.coli expressed His-TEIF protein.

DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation.

NAT10 (N-acetyltransferase 10) is a protein with histone acetylation activity and primarily identified to be involved in regulation of telomerase activity. The presented research shows its transcriptional activation by genotoxic agents and possible role in DNA damage. NAT10 mRNA could be markedly increased by using hydrogen peroxide (H2O2) or cisplatin in a dose- and time-dependent way, and the immunofluorescent staining revealed that the treatment of H2O2 or cisplatin induced focal accumulation of NAT10 protein in cellular nuclei.