Survival Time among Young and Old Breast Cancer Patients in Relation to Circulating Blood-Based Biomarkers, Acute Radiation Skin Reactions, and Tumour Recurrence.

INTRODUCTION: It has been suggested that age could influence the treatment-induced side effects and survival time of cancer patients. The influence of age on blood-based biomarkers, acute radiation skin reactions (ARSRs), and survival time of breast cancer patients was analysed. MATERIALS AND METHODS: Two hundred ninety-three individuals, 119 breast cancer patients, and 174 healthy blood donors were included. RESULTS: Before radiotherapy (RT), decreased levels of lymphocytes, interleukin 2, platelet-derived growth factors, and tumour necrosis factor but increased levels of monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, C-reactive protein, and macrophage inflammatory protein 1b (MIP1b) were detected in the patient group. All of the patients developed ARSRs and intensity of ARSRs was inversely related to the MIP1b level before RT. Fifteen out of 119 (13%) patients deceased during follow-up time. No influence of age (≤50 compared to >50 years) on survival time was detected (p = 0.442). Tumour recurrence, found in 11 out of 119 (9%) patients, had impact on survival time of these patients (p < 0.001). CONCLUSIONS: The level of circulating MIP1b before RT was associated with intensity of ARSRs. Tumour recurrence, but not age, was associated with poor survival time. Analysis of circulating MIP1b was low cost, rapid, and could be done in routine laboratory facility. Since RT almost always induces ARSRs, the possibility of using MIP1b as a prognostic biomarker for ARSRs is of interests for further investigation.

Genomic Insights Into Clinical Shiga Toxin-Producing Escherichia coli Strains: A 15-Year Period Survey in Jönköping, Sweden.

Shiga toxin-producing Escherichia coli (STEC) are important foodborne pathogens that can cause human infections ranging from asymptomatic carriage to bloody diarrhea (BD) and fatal hemolytic uremic syndrome (HUS). However, the molecular mechanism of STEC pathogenesis is not entirely known. Here, we demonstrated a large scale of molecular epidemiology and in-depth genomic study of clinical STEC isolates utilizing clinical and epidemiological data collected in Region Jönköping County, Sweden, over a 15-year period. Out of 184 STEC isolates recovered from distinct patients, 55 were from patients with BD, and 129 were from individuals with non-bloody stools (NBS). Five individuals developed HUS. Adults were more associated with BD. Serotypes O157:H7, O26:H11, O103:H2, O121:H19, and O104:H4 were more often associated with BD. The presence of Shiga toxin-encoding gene subtypes stx 2a, stx 2a + stx 2c, and stx 1a + stx 2c was associated with BD, while stx 1 a was associated with milder disease. Multiplex virulence and accessory genes were correlated with BD; these genes encode toxins, adhesion, autotransporters, invasion, and secretion system. A number of antimicrobial resistance (AMR) genes, such as aminoglycoside, aminocoumarin, macrolide, and fluoroquinolone resistance genes, were prevalent among clinical STEC isolates. Whole-genome phylogeny revealed that O157 and non-O157 STEC isolates evolved from distinct lineages with a few exceptions. Isolates from BD showed more tendency to cluster closely. In conclusion, this study unravels molecular trait of clinical STEC strains and identifies genetic factors associated with severe clinical outcomes, which could contribute to management of STEC infections and disease progression if confirmed by further functional validation.

Influence of single nucleotide polymorphisms among cigarette smoking and non-smoking patients with coronary artery disease, urinary bladder cancer and lung cancer.

INTRODUCTION: Cigarette smoke is suggested to be a risk factor for coronary artery disease (CAD), urinary bladder cancer (UBCa) or lung cancer (LCa). However, not all heavy smokers develop these diseases and elevated cancer risk among first-degree relatives suggests an important role of genetic factor. METHODS: Three hundred and ten healthy blood donors (controls), 98 CAD, 74 UBCa and 38 LCa patients were included in this pilot study. The influence of 92 single nucleotide polymorphisms (SNPs) and impact of cigarette smoking were analysed. RESULTS: Out of 92 SNPs tested, differences in distribution of 14 SNPs were detected between controls and patient groups. Only CTLA4 rs3087243 showed difference in both CAD and UBCa patient group compared to control group. Stratified by smoking status, the impact of smoking was associated to frequencies of 8, 3 and 4 SNPs in CAD, UBCa, LCa patients, respectively. None of these 92 SNPs showed a statistically significant difference to more than one type of disease among smoking patients. In non-smoking patients, 7, 3 and 6 SNPs were associated to CAD, UBCa, LCa, respectively. Out of these 92 SNPs, CTLA4 rs3087243 was associated to both non-smoking CAD and UBCa. The XRCC1 rs25487 was associated to both non-smoking UBCa and LCa. CONCLUSION: SNPs might be important risk factors for CAD, UBCa and LCa. Distribution of the SNPs was specific for each patient group, not a random event. Impact of cigarette smoking on the disease was associated to the specific SNP sequences. Thus, smoking individuals with SNPs associated to risk of these serious diseases is an important target group for smoking cessation programs.

Impact of Cigarette Smoking and Head and Neck Squamous Cell Carcinoma on Circulating Inflammatory Biomarkers.

INTRODUCTION: Smoking induces inflammation and an immune response. A cancer-related inflammatory response has been seen in smoking and nonsmoking head and neck squamous cell carcinoma (HNSCC) patients. OBJECTIVES: The aim of this study was to analyze the possible separated effects of smoking or HNSCC on 18 inflammatory or immune regulatory biomarkers. METHODS: Fifty-one nonsmoking and 36 smoking pretreated HNSCC patients and 101 nonsmoking and 39 smoking controls were included in this study. The levels of 18 inflammatory or immune regulatory biomarkers were analyzed. A multivariable linear regression model was used to predict the impact of smoking and HNSCC on the levels of the biomarkers. RESULTS: Smoking had the highest impact on total WBC, IFN-γ, and MCP-1 levels. The highest impact of HNSCC was found on neutrophils, neutrophil-to-lymphocyte ratio, HsCRP, MIP-1b, and TNF-α levels. CONCLUSION: IdentifyingHNSCC or smoking-related inflammatory biomarkers might contribute to the understanding of the immune response in HNSCC patients. This study could provide information of inflammatory biomarkers in HNSCC patients.

The Influence of Adjuvant Radiotherapy and Single Nucleotide Polymorphisms on Circulating Immune Response Cell Numbers and Phenotypes of Patients With Breast Cancer.

BACKGROUND/AIM: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. MATERIALS AND METHODS: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. RESULTS: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. CONCLUSION: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.

The Influence of Single Nucleotide Polymorphisms and Adjuvant Radiotherapy on Systemic Inflammatory Proteins, Chemokines and Cytokines of Patients With Breast Cancer.

Independently of tumour and treatment modulation, the host immune response status plays an important role in the clinical outcome of patients with cancer. The influence of single nucleotide polymorphisms (SNPs) and adjuvant radiotherapy (RT) on the systemic immune response status of patients with breast cancer was investigated. MATERIALS AND METHODS: Eighty-six female patients recovering from breast cancer surgery were investigated. As a control cohort, 82 healthy female blood donors were used. Blood-based SNPs, plasma C-reactive protein (CRP), cytokines and chemokines were analyzed for this purpose. RESULTS: Independently of tumour stage and hormone receptor status, dysregulation of plasma CRP, chemokine (C-C motif) ligand 4 (CCL4) and interleukin 2 (IL2), but not CCL5, CCL2, platelet-derived growth factor, IL6, IL10, IL12, interferon-gamma or tumour necrosis factor alpha were detected in the patients when compared to controls. The extent of alteration in plasma levels of CRP and IL2 patients was significantly associated with SNPs in CRP rs1800947 and IL2 rs6822844, respectively. These SNPs had no influence on the levels of corresponding plasma biomarkers in the healthy controls. Adjuvant RT reduced plasma CRP and CCL5 levels in patients with regards to CRP rs1800947CC, CCL5 rs2107538GG and CCL5 rs2280789AA sequences. CONCLUSION: Dysregulation of immune responses, as indicated by plasma levels of CRP, CCL4 and IL2 were found in patients with breast cancer despite the removal of the tumour mass. The benefit of adjuvant RT, as indicated by reduced plasma amounts of inflammatory protein CRP and chemokine CCL5 were based on the SNPs of the patients. Analyses of blood-based SNPs, plasma CRP, IL2 and CCL5 are low cost, rapid and can be carried out using general laboratory facilities while requiring only a peripheral blood sample. The possibility of using these blood-based biomarkers as an indicator of patient immune status for selection of individual patient treatment warrants further investigation.

Cigarette smoking affects microRNAs and inflammatory biomarkers in healthy individuals and an association to single nucleotide polymorphisms is indicated.

BACKGROUND: Cigarette smoke induces inflammation and remodels immune response. Genetic and epigenetic alterations might be involved in the pathogenesis of smoking related diseases. In this study, we investigated the effect of smoking on systemic inflammation biomarkers and epigenetic changes at microRNA (miRNA) expression level. We also examined if the levels of inflammatory biomarkers were associated with selected single nucleotide polymorphisms (SNPs). METHOD: From 39 smokers and 101 non-smokers, levels of total white blood cells (WBCs) and its subpopulations, plasma cytokines/chemokines/proteins and miRNAs were analysed. For three biomarkers, C-reactive protein (CRP), MCP-1 and IFN-γ that were affected by smoking, the influence of SNPs was analyzed. RESULT: Elevated levels of total WBCs, neutrophils, monocytes, lymphocytes, CRP, MCP-1, IFN-γ and lower levels of miR-21 were detected in smokers. The elevated levels of IFN-γ in smokers was only statistically significantly associated with rs2069705 AG/GG SNP-genotype. CONCLUSIONS: A lower level of oncomir miRNA-21 and a higher level of immune modelling cytokine IFN-γ detected in smokers could be a protective immune response to cigarette smoke. The higher level of IFN-γ in smokers with a specific SNP genotype also suggests that a genetic interaction with smoking might predict the pathobiology of smoking related disease.

Shiga Toxin-Producing Escherichia coli Infection in Jönköping County, Sweden: Occurrence and Molecular Characteristics in Correlation With Clinical Symptoms and Duration of stx Shedding.

Shiga toxin-producing Escherichia coli (STEC) cause bloody diarrhea (BD), hemorrhagic colitis (HC), and even hemolytic uremic syndrome (HUS). In Nordic countries, STEC are widely spread and usually associated with gastrointestinal symptoms and HUS. The objective of this study was to investigate the occurrence of STEC in Swedish patients over 10 years of age from 2003 through 2015, and to analyze the correlation of critical STEC virulence factors with clinical symptoms and duration of stx shedding. Diarrheal stool samples were screened for presence of stx by real-time PCR. All STEC isolates were characterized by DNA microarray assay and PCR to determine serogenotypes, stx subtypes, and presence of intimin gene eae and enterohaemolysin gene ehxA. Multilocus sequencing typing (MLST) was used to assess phylogenetic relationships. Clinical features were collected and analyzed using data from the routine infection control measures in the county. A total of 14,550 samples were enrolled in this 12-years period study, and 175 (1.2%) stools were stx positive by real-time PCR. The overall incidence of STEC infection was 4.9 cases per 100,000 person-years during the project period. Seventy-five isolates, with one isolate per sample were recovered, among which 43 were from non-bloody stools, 32 from BD, and 3 out of the 75 STEC positive patients developed HUS. The presence of stx2 in both stools and isolates were associated with BD (p = 0.008, p = 0.05), and the presence of eae in isolates was related to BD (p = 0.008). The predominant serogenotypes associated with BD were O157:H7, O26:H11, O121:H19, and O103:H2. Isolates from HUS were O104:H4 and O98: H21 serotypes. Phylogenetic analysis revealed our strains were highly diverse, and showed close relatedness to HUS-associated STEC collection strains. In conclusion, the presence of stx2 in stool was related to BD already at the initial diagnostic procedure, thus could be used as risk predictor at an early stage. STEC isolates with stx2 and eae were significantly associated with BD. The predominant serotypes associated with BD were O157:H7, O26:H11, O121:H19, and O103:H2. Nevertheless, the pathogenic potential of other serotypes and genotypes should not be neglected.

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals.

Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking-related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty-four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never-users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C-reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8dim cells in the lymphocyte group, CD13+  CD11+ , CD13+  CD14+ , CD13+  CD56+ cells in the monocyte group and CD13+  CD11+ , CD13+  CD56+ cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8+  GZB+ cells in the CD8dim group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking-related disease and the variations observed in clinical outcomes.

The use of rapid and cost-effective blood-based biomarkers in combination with tumour TNM stage for individual head and neck cancer patient treatment selection.

Head and neck (H&N) cancer is an aggressive disease and the incidence has increased in younger population worldwide. Tumour TNM staging is the main basis for treatment decision despite significant variation in clinical outcome. Survival time of these patients has marginally improved during the last 30 years. Various biomarkers with cumbersome analysis, high cost, time consumption and requirement of special laboratory facilities have been investigated. However, none of these biomarkers have been shown to be suitable to use for individual H&N cancer patient treatment selection in the clinic. For practical use in clinical settings, the given biomarkers must be simple to analyse, rapid, cost effective and available in routine laboratories. With this intension, we suggested the combination of standard TNM staging and biomarkers associated with inflammation such as neutrophils, neutrophil to lymphocyte ratio, plasma C-reactive protein or plasma tumour necrosis factor alpha (TNFa) and single-nucleotide polymorphism in TNFa rs1800629 using blood-based analysis. The optimal treatment outcome of H&N cancer by using combination of TNM stage and these blood-based biomarkers for individual patient selection need further investigation.

Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients.

OBJECTIVE: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. METHODS: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. RESULTS: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFα) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival. CONCLUSION: Genetic variation of the TNFα rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.

Norovirus Dynamics in Wastewater Discharges and in the Recipient Drinking Water Source: Long-Term Monitoring and Hydrodynamic Modeling.

Norovirus (NoV) that enters drinking water sources with wastewater discharges is a common cause of waterborne outbreaks. The impact of wastewater treatment plants (WWTPs) on the river Göta älv (Sweden) was studied using monitoring and hydrodynamic modeling. The concentrations of NoV genogroups (GG) I and II in samples collected at WWTPs and drinking water intakes (source water) during one year were quantified using duplex real-time reverse-transcription polymerase chain reaction. The mean (standard deviation) NoV GGI and GGII genome concentrations were 6.2 (1.4) and 6.8 (1.8) in incoming wastewater and 5.3 (1.4) and 5.9 (1.4) log10 genome equivalents (g.e.) L-1 in treated wastewater, respectively. The reduction at the WWTPs varied between 0.4 and 1.1 log10 units. In source water, the concentration ranged from below the detection limit to 3.8 log10 g.e. L-1. NoV GGII was detected in both wastewater and source water more frequently during the cold than the warm period of the year. The spread of NoV in the river was simulated using a three-dimensional hydrodynamic model. The modeling results indicated that the NoV GGI and GGII genome concentrations in source water may occasionally be up to 2.8 and 1.9 log10 units higher, respectively, than the concentrations measured during the monitoring project.

Shiga Toxin-Producing Escherichia coli in Diarrheal Stool of Swedish Children: Evaluation of Polymerase Chain Reaction Screening and Duration of Shiga Toxin Shedding.

BACKGROUND: Shiga toxin (Stx)-producing Escherichia coli (STECs) are the most common cause of acute renal failure in children. The present study evaluated a 10-year STEC polymerase chain reaction screening regimen in children. METHODS: All routine stool culture specimens from patients below 10 years of age (n = 10 342) from May 2003 through April 2013 in the County of Jönköping, Sweden, were included. Patients were divided in 1 group where analyses of STEC were requested by the clinician (n = 2366) and 1 screening group (n = 7976). Patients who were positive for STEC were tested weekly until they were negative. Clinical data were collected through a questionnaire and by reviewing medical records. RESULTS: In specimens from 191 patients, stx was found (162 index cases). The prevalence was 1.8% in the requested group and 1.5% in the screening group (P = .5). Diarrhea was the most frequent symptom reported in 156 cases and of these 29 (19%) had hemorrhagic colitis (HC) and 7 children developed hemolytic uremic syndrome (HUS). No difference regarding severity of symptoms between the groups was found. Stx2 predominated in cases with HC (P < .0001) and HUS (P = .04). Median stx shedding duration was 20 days (1-256 days), and no difference in duration was seen between stx types (P = .106-1.00) and presence of eaeA (P = .72). CONCLUSIONS: Most STEC cases were found in the screening group with comparable prevalence and disease severity as in patients where analysis was requested. Furthermore, non-O157 serotypes caused severe disease when carrying stx2, and prolonged shedding of STEC may be a risk for transmission.

Real-Time PCR Typing of Escherichia coli Based on Multiple Single Nucleotide Polymorphisms--a Convenient and Rapid Method.

BACKGROUND: Healthcare-associated infections caused by Escherichia coli and antibiotic resistance due to extended-spectrum beta-lactamase (ESBL) production constitute a threat against patient safety. To identify, track, and control outbreaks and to detect emerging virulent clones, typing tools of sufficient discriminatory power that generate reproducible and unambiguous data are needed. METHODS: A probe based real-time PCR method targeting multiple single nucleotide polymorphisms (SNP) was developed. The method was based on the multi locus sequence typing scheme of Institute Pasteur and by adaptation of previously described typing assays. RESULTS: An 8 SNP-panel that reached a Simpson's diversity index of 0.95 was established, based on analysis of sporadic E. coli cases (ESBL n = 27 and non-ESBL n = 53). This multi-SNP assay was used to identify the sequence type 131 (ST131) complex according to the Achtman's multi locus sequence typing scheme. However, it did not fully discriminate within the complex but provided a diagnostic signature that outperformed a previously described detection assay. Pulsed-field gel electrophoresis typing of isolates from a presumed outbreak (n = 22) identified two outbreaks (ST127 and ST131) and three different non-outbreak-related isolates. Multi-SNP typing generated congruent data except for one non-outbreak-related ST131 isolate. CONCLUSIONS: We consider multi-SNP real-time PCR typing an accessible primary generic E. coli typing tool for rapid and uniform type identification.

Humoral response to influenza vaccination in relation to pre-vaccination antibody titres, vaccination history, cytomegalovirus serostatus and CD4/CD8 ratio.

BACKGROUND: Annual vaccination against influenza virus is generally recommended to elderly and chronically ill, but the relative importance of factors influencing the outcome is not fully understood. METHODS: In this study of 88 individuals all aged 69 years, the increase in haemagglutinin-inhibiting (HI) antibodies to trivalent inactivated influenza vaccine was correlated with HI titres before vaccination, prior vaccinations against influenza, cytomegalovirus serostatus and, as an estimate of immune risk profile, the ratio between CD4 + and CD8 + T cells. RESULTS: Vaccine responses were impaired by high pre-existing HI antibody titres. For influenza B repeated vaccinations and an inverse CD4/CD8 ratio had a negative impact on the vaccine response. Cytomegalovirus seropositivity had no apparent effect on HI titres before or after vaccination. CONCLUSIONS: It is concluded that both pre-existing HI antibodies and previous vaccinations to influenza may influence the humoral response to influenza vaccination and that a CD4/CD8 ratio < 1 may indicate an impaired ability to respond to repeated antigenic stimulation.

Prognostic significance of PLA2G4C gene polymorphism in patients with stage II colorectal cancer.

BACKGROUND: Phospholipase A2 Group IV C (PLA2G4C) catalyzes the release of certain fatty acids from phospholipids and plays a role in a range of physiological functions, such as remodeling of cell membranes and the production of prostaglandins. Furthermore, it has been proposed that PLA2G4C plays an important role in breast cancer cell chemotaxis. This study aimed to investigate the effect of a single nucleotide polymorphism (SNP) rs1549637 (T>A) of the PLA2G4C gene on the prognosis of colorectal cancer (CRC). MATERIAL AND METHODS: Whole blood DNA was extracted from 381 patients with CRC and 618 controls, and a TaqMan SNP genotyping assay was used to determine the distribution of the genotypes. Cancer-specific and disease-free survival was analyzed by Kaplan-Meier graphs and by uni- and multivariable Cox regression. RESULTS: The cancer-specific survival differed between the genotypes (p = 0.019) and the carriers of the A allele were associated with the highest risk of CRC death, with a hazard ratio (HR) of 1.72 [95% confidence interval (CI) 1.17-2.53, p = 0.006] compared with homozygous carriers of the T allele. This increased mortality in the carriers with the allele A was especially marked in stage II with an HR of 3.84 (95% CI 1.51-9.78, p = 0.005). CONCLUSION: The A allele in PLA2G4C SNP (rs1549637) is associated with a worse prognosis in patients with CRC, especially in stage II disease, and it could be a potential prognostic biomarker in the planning of individual adjuvant therapy in stage II patients.

CD93 gene polymorphism is associated with disseminated colorectal cancer.

PURPOSE: Cluster of differentiation 93 (CD93) is involved in apoptosis and inflammation and has a suggested role in angiogenesis, and all of which are involved in the development and dissemination of cancer. We evaluated the expression of CD93 and the association with two single nucleotide polymorphisms (SNPs), rs2749812 and rs2749817, as possible biomarkers in colorectal cancer (CRC). METHODS: Tissue levels and plasma levels of CD93 were measured using an enzyme-linked immunosorbent assay (ELISA). Expression of CD93 was determined by immunohistochemistry, western blot and gene expression analysis. Genotype frequencies were established for the SNPs by real-time polymerase chain reaction (PCR), and the association with tumour stage and survival was analysed. RESULTS: Total CD93 levels were 82% higher (P < 0.001) in tumours compared to matched normal tissues. Mean levels of soluble CD93 in plasma were 30% lower (P < 0.001) in the patients compared to the controls. The T/T genotype of SNP rs2749817 was more common in stage IV patients, with consequently higher risk of CRC death (T/T vs. C/C and C/T; hazard ratio (HR) = 1.73, 95% confidence interval (CI) = 1.11-2.67, P = 0.014), and was associated with a higher risk of CRC recurrence after radical operation (T/T vs. C/C and C/T; HR = 2.07, CI = 1.22-3.51, P = 0.007). CONCLUSIONS: We showed that the T/T genotype of SNP rs2749817 is associated with disseminated cancer at diagnosis and an increased recurrence rate after radical operation. Patients with this genotype may benefit from early identification.

Common 4977 bp deletion and novel alterations in mitochondrial DNA in Vietnamese patients with breast cancer.

Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and ageing. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in breast cancer (BC). The aim of this study was to investigate the frequency of mtDNA 4977 bp deletion in BC tissue and its association with clinical factors. We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 106 Vietnamese patients with BC by sequencing PCR products. The mtDNA 4977 bp deletion was significantly more frequent in normal tissue in comparison with paired cancer tissue. Moreover, the incidence of the 4977 bp deletion in BC tissue was significantly higher in patients with estrogen receptor (ER) positive as compared with ER negative BC tissue. Preliminary results showed, in cancerous tissue, a significantly higher incidence of novel deletions in the group of patients with lymph node metastasis in comparison with the patients with no lymph node metastasis. We have found 4977 bp deletion in mtDNA to be a common event in BC and with special reference to ER positive BC. In addition, the novel deletions were shown to be related to lymph node metastasis. Our finding may provide complementary information in prediction of clinical outcome including metastasis, recurrence and survival of patients with BC.

Perforin, CD28 and CD95 expression in circulating CD4 and CD8 cells as predictors of head and neck (H&N) cancer patient survival.

Long-term survival of H&N cancer patients has not improved significantly over the last 30 years. The possibility of using circulating blood cell phenotypes as a prognostic biomarker of H&N cancer patient was investigated in this study. Pre-treatment, circulating T lymphocyte subpopulations as well as the survival time of the patients in question were studied. Upregulated CD4+ perforin+ and CD8+ CD95+ but downregulated CD4+ CD28+ (p < 0.001) were detected in H&N cancer patients. With 3 years of follow-up time, an increase in the frequency of the pre-treatment, circulating CD4+ perforin+ cells and CD8+ perforin+ cells was showed to have reverse effects on the survival time in H&N cancer patients (p < 0.01). Detection of perforin+ frequency in CD4+ and CD8+ lymphocyte by FACS is fast, simple and cost-effective. A potential role of perforin expression in CD4+ and CD8+ cells as a prognostic biomarker for H&N cancer patient in the clinical setting was suggested.