Variation In Cancer Patients Research Articles

Online communication skill training of patients with cancer: A test of the behavioral intention predictive framework for communication skills

ObjectiveTo assess the Behavioral Intention Predictive Framework's utility in explaining variation in cancer patients' strong behavioral intention (SBI) to use LEAPS (Listen, Educate, Assess, Partner, Support) communication skills after viewing training videos. MethodsNinety-eight patients were enrolled through anonymized online platforms to view LEAPS training videos, complete background and communication questionnaires and report their SBI to use LEAPS skills. ResultsOn average, patients indicated SBI to use 6 of 13 skills and 46% of patients expressed SBI across individual skills. The framework explained 27.7% of the adjusted variance in SBI with significant predictors of frequent past use of LEAPS-related shared decision-making behaviors, poor emotional health, being rarely accompanied to visits and positive ratings of narrative videos. Finally, 21.7% of the adjusted variance in problem communication was explained by infrequent use of LEAPS-related information behaviors, patient accompaniment of another adult and positive narrative scores. ConclusionPatients SBI to use multiple LEAPS skills and past problem communication were explained by framework predictors. InnovationDespite theoretical and empirical evidence that behavioral intention significantly predicts behavior, it has not been studied in patient communication research. Application of the novel framework to LEAPS training videos contributes an innovative address of this research gap.

Exploring hematic crasis variations in cancer patients following SARS-CoV-2 vaccination: a real-practice study

SARS-CoV-2 vaccination is strongly recommended, particularly for fragile patients such as those undergoing active oncological treatments. It is crucial to conduct post-marketing surveillance in this patient population. In our study, we conducted a retrospective analysis of real-world data, including 136 patients who received SARS-CoV-2 vaccines and were undergoing anticancer treatments between March 1st and June 30th, 2021. All patients received mRNA vaccines, namely Pfizer-BioNTech’s COMIRNATY (BNT162b2 mRNA) and Moderna’s mRNA-1273 COVID-19 vaccines. We collected blood samples from the patients one week to 10 days before and after vaccine administration to assess full blood count with white cell differentials. Additionally, we monitored serology titers to detect any previous SARS-CoV-2 infection before hospital admission and tracked changes over time. Our findings revealed a significant occurrence of leukopenia following both the first and second vaccine doses among patients receiving chemotherapy and chemo-immunotherapy. Importantly, this effect was independent of demographic factors such as sex, age, and Body Mass Index. In the chemo-immunotherapy treated group, we observed that concomitant immune-mediated diseases were significantly associated with leukopenia following the second vaccine dose. Notably, in healthy subjects, transient neutropenia was recognized as an adverse event following vaccination. The observed lymphocytopenia during SARS-CoV-2 infection, combined with the impact on leukocyte counts observed in our study, underscores the need for larger post-marketing surveillance studies. Despite a treatment delay occurring in 6.6% of patients, the administration of mRNA vaccines did not have a significant impact on the treatment schedule in our series. These findings from a real-world setting provide valuable insights and suggest avenues for further prospective studies to explore potential complex interactions specific to this patient population.

METB-09. GERMLINE PATHOGENIC VARIANTS IN 838 PEDIATRIC BRAIN TUMOR PATIENTS

Abstract The genetic contribution of rare pathogenic germline variation in cancer patients without a family history remains unclear. We sought to characterize the prevalence, spectrum, and clinical significance of pathogenic germline variation in cancer predisposition genes (CPGs) in pediatric brain tumor patients. Paired tumor and normal whole genome or exome sequencing was performed for 838 patients in the Pediatric Brain Tumor Atlas (PBTA). Rare variants in 196 CPGs were annotated as pathogenic (P) or likely pathogenic (LP) in an automated manner consistent with American College of Medical Genetics criteria and reviewed by an interdisciplinary panel. To assess enrichment, the frequency of CPG P-LP variants in cases was compared to the gnomAD v3.1 cancer-free control cohort (n=74,023). Second hit, mutational signature, and gene set enrichment analyses (GSEA) were performed on matched tumor sequencing to characterize differences in patients with and without germline P-LP variants in DNA repair genes. We observed 178 germline CPG P-LP variants in 163 PBTA patients (19.5%). CPG P-LP variants were most prevalent among Neurofibroma plexiform patients (64.3%), and NF1 and TSC2 harbored the most significant P-LP variant burden compared to controls (OR=69.5, p=2.4E-23, CI=34.6-137 and OR=357, p=1.1E-14, CI=71-3669, respectively). DNA repair gene P-LP variants were enriched in cases compared to controls (OR=4.4, p=8.3E-30). Patients harboring mismatch repair (MMR) gene P-LP variants exhibited significantly higher tumor-associated MMR-deficiency mutational signature exposures (p<0.05) and DNA repair GSEA scores relative to other patients (p=0.04). Second hit SNVs in tumors were identified in four patients with P-LP germline variants in NF1 (n=2), APC (n=1), and SUFU (n=1). Germline P-LP variants are enriched in PBTA patients, and DNA repair variants are predictive of repair-deficiency signatures in tumor samples. Our work emphasizes the need for germline sequencing to inform patient care.

Clinical treatment pathways utilization in an outpatient academic cancer center.

323 Background: Clinical treatment pathway (CTP) tools have been incorporated into oncology practices to help standardize treatment, reduce care variation in cancer patients, and move towards value-based care. CTP tools incorporate the latest guidelines and are developed through multidisciplinary committees. Treatment decisions are prioritized by efficacy, toxicity, and cost to improve quality and value. This is especially important in cancer care which is associated with high drug costs. However, use and implementation of CTP tools has been met with mixed reviews and published data from academic medical centers are limited. Methods: Outpatient treatment decisions for patients across different cancer types, including colorectal, gastroesophageal, and breast cancers from July 2018 to March 2020 at an urban NCI-designated cancer center were evaluated. Every treatment decision was evaluated in relation to physician utilization of CTP tools. Treatment decisions were categorized as choosing a CTP recommended option ( pathways dependent), not choosing a CTP recommended option ( pathways independent), or not using the CTP tool at all ( non-pathways). Descriptive statistics and significance testing were used to explore CTP utilization over time, physician years in practice, cancer type, and cancer stage. Multinomial and binary logistic regression models were used to evaluate associated factors with CTP utilization. Results: During the study period, 1,007 treatment decisions were identified. Of these, 76% were pathways dependent, 13% were pathways independent, and 11% were non-pathways. CTP utilization was statistically significant in association with cancer type, cancer stage, physician years in practice, and year of encounter. In multinomial logistic regression models, physicians with more years in practice were more likely to be pathways independent and non-pathways than pathways dependent. Physicians treating colorectal or gastroesophageal cancer were more likely to be pathways independent [OR 3.27; 95% CI: 1.98-5.42 and OR 2.25; 95% CI: 1.12-4.49, respectively] or non-pathways [OR 2.98; 95% CI: 1.65-5.37 and OR 3.21; 95% CI: 1.58-6.54, respectively] than pathways dependent compared to physicians treating breast cancer. Treatment decisions for patients with either stage 2 and stage 4 cancers were more likely to be pathways independent than stage 1 cancers [OR 4.13; 95% CI: 1.44-11.84 and OR 4.37; 95% CI: 1.27-15.04, respectively]. Conclusions: This study found that a large proportion of treatment decisions for patients across different cancer types were made utilizing CTP tools, but utilization varies according to cancer type, stage, and physician years in practice. Further research is needed to better understand the physician decision making process and implementation of CTP tools to drive improvement in design, education, and training.

Impacts of cachexia progression in addition to serum IgG and blood lymphocytes on serum nivolumab in advanced cancer patients.

Serum nivolumab concentrations exhibit a large variation in cancer patients. Cancer cachexia inducing systemic inflammation promotes the elimination of endogenous proteins, while its association with serum nivolumab remains unclear. The present study aimed to evaluate the impacts of cachexia progression in addition to blood components on serum nivolumab in cancer patients. Thirty-eight non-small-cell lung cancer or renal cell cancer patients receiving biweekly intravenous nivolumab were enrolled. Blood samples were collected just before dosing at the 7th administration of nivolumab or later. Serum nivolumab together with serum proteins, inflammatory markers, and peripheral blood leukocytes were determined. Cancer cachexia was classified using the Glasgow Prognostic Score (GPS). Immune-related adverse events (irAEs) were monitored during the study period. Cancer patients had a large variation in serum nivolumab concentrations (interquartile range, 12-21µg/mL per mg/kg). The serum nivolumab concentration was positively correlated with serum albumin, while negatively associated with serum globulin and immunoglobulin G (IgG). A negative correlation was observed between serum nivolumab and blood lymphocytes. Regarding cachexia progression, the patients with GPS 2 had a higher serum interleukin-6 concentration and a lower serum nivolumab concentration than those with GPS 0 or 1. The GPS, serum IgG, and blood lymphocytes were identified as independent variables for serum nivolumab. The incidence of irAEs was not associated with the nivolumab dose or serum nivolumab. Cachexia progression had a negative impact on serum nivolumab in cancer patients. The interindividual variation in serum nivolumab was characterized by cachexia progression in addition to blood components.

Clinical treatment pathways utilization in an outpatient academic cancer center.

e18673 Background: Clinical treatment pathway (CTP) tools have been incorporated into oncology practices to help standardize treatment, reduce care variation in cancer patients, and move towards value-based care. CTP tools incorporate the latest guidelines and are developed through multidisciplinary committees. Treatment decisions are prioritized by efficacy, toxicity, and cost to improve quality and value. This is especially important in cancer care which is associated with high drug costs. However, use and implementation of CTP tools has been met with mixed reviews and published data from academic medical centers are limited. Methods: Outpatient treatment decisions for patients across different cancer types, including colorectal, gastroesophageal, and breast cancers from July 2018 to March 2020 at an urban NCI-designated cancer center were evaluated. Every treatment decision was evaluated in relation to physician utilization of CTP tools. Treatment decisions were categorized as choosing a CTP recommended option ( pathways dependent), not choosing a CTP recommended option ( pathways independent), or not using the CTP tool at all ( non-pathways). Descriptive statistics and significance testing were used to explore CTP utilization over time, physician years in practice, cancer type, and cancer stage. Multinomial and binary logistic regression models were used to evaluate associated factors with CTP utilization. Results: During the study period, 1,007 treatment decisions were identified. Of these, 76% were pathways dependent, 13% were pathways independent, and 11% were non-pathways. CTP utilization was statistically significant in association with cancer type, cancer stage, physician years in practice, and year of encounter. In multinomial logistic regression models, physicians with more years in practice were more likely to be pathways independent and non-pathways than pathways dependent. Physicians treating colorectal or gastroesophageal cancer were more likely to be pathways independent [OR 3.27; 95% CI: 1.98-5.42 and OR 2.25; 95% CI: 1.12-4.49, respectively] or non-pathways [OR 2.98; 95% CI: 1.65-5.37 and OR 3.21; 95% CI: 1.58-6.54, respectively] than pathways dependent compared to physicians treating breast cancer. Treatment decisions for patients with either stage 2 and stage 4 cancers were more likely to be pathways independent than stage 1 cancers [OR 4.13; 95% CI: 1.44-11.84 and OR 4.37; 95% CI: 1.27-15.04, respectively]. Conclusions: This study found that a large proportion of treatment decisions for patients across different cancer types were made utilizing CTP tools, but utilization varies according to cancer type, stage, and physician years in practice. Further research is needed to better understand the physician decision making process and implementation of CTP tools to drive improvement in design, education, and training.

The role of Virostatic genes in modulating Immune Checkpoints in Epstein-Barr Virus associated Tumors

Abstract Epstein-Barr Virus (EBV) is a complex oncovirus that infects around 90% of adults. Most primary infections remain asymptomatic but result in lifelong infection. EBV can drive lethal malignancies of both lymphoid (e.g. Burkitt lymphoma) and epithelial origins (e.g. Stomach Adenocarcinoma). Despite decades of research, the exact molecular mechanisms of EBV and host immune system interactions that lead to tumorigenesis remain elusive. Through systematic analyses of high-throughput sequencing data from >1000 patients with different cancer types, we identified twelve EBV transcripts, including LMP1 and LMP2, which when overexpressed, significantly suppressed viral reactivation. These ‘virostatic genes’ had frequent missense and nonsense variations in cancer patients, disrupting their ability to restrict EBV reactivation. We also found that viral reactivation by classical chemical inducers up-regulates the expression of Programmed Death-Ligand 1 (PD-L1). Further analyses of the same RNA-seq dataset classified EBV+ tumors into two molecular subtypes based on expression pattern of upstream regulatory immune-related genes and Immune Checkpoint (IC) markers, including PD-L1. Overexpression of virostatic genes in lymphoblastic cells significantly repressed cellular PD-L1 transcription, leading us to hypothesize that a combination of IC and virostatic gene modulation may have synergistic benefits for immunotherapy of EBV-associated cancers.

Day-to-day and within-day biological variation of cell-free DNA.

BackgroundNumerous studies have shown that cell-free DNA (cfDNA) levels may serve as a non-invasive biomarker of a broad spectrum of acute and chronic pathologies. However, in order to make clinical decisions based on cfDNA measurements, it is essential to understand the magnitude of biological variation so this variation is not confused with a variation that actually represent a clinically relevant change. The present study was designed to evaluate the biological variation of cfDNA in healthy subjects and lung cancer patients.MethodsPlasma samples were collected from 33 healthy subjects and ten lung cancer patients over three days, as well as during the same day. CfDNA was quantified using droplet digital PCR. Biological variation data was estimated using mixed models.FindingsThe within-subject variation was 25% and the between-subject variation was 30%. The reference change value for the healthy subjects was 70%. There was no systematic difference in cfDNA levels from day-to-day (p = 0⋅61), but there was a significant decline during the day (p<0⋅01). The within-subject variation in cancer patients was comparable to healthy subjects, whereas the between-subject variation was much larger (139%). No systematic differences from day-to-day were observed for the cancer patients (p>0⋅3).InterpretationOur findings show that cfDNA levels fluctuate significantly during the day and exhibit considerable within-subject variation. Thus, the data presented offer a substantial contribution to the interpretation of the clinical significance of cfDNA.FundingLæge Sofus Carl Emil Friis og hustru Olga Doris Friis' Legat, Harboefonden, and Dagmar Marshalls Fond.

Impact of CYP genotype and inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients.

Clinical responses to oral tramadol show a large variation in cancer patients. This study aimed to evaluate the impacts of cytochrome P450 (CYP) genotype and serum inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients. The predose plasma concentrations of tramadol and its demethylated metabolites were determined at day 4 or later in 70 Japanese cancer patients treated with oral tramadol. The CYP genotypes, serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and the duration of tramadol treatment were evaluated. The CYP2D6 genotype did not affect the plasma tramadol concentration. The plasma concentration of O-desmethyltramadol and its ratio to tramadol were lower in the CYP2D6 intermediate and poor metabolizer (IM + PM) group than in the normal metabolizer (NM) group (P = 0.002 and P = 0.023). The plasma concentration of N-desmethyltramadol and its ratio to tramadol were higher in the CYP2D6 IM + PM group than in the NM group (P = 0.001 and P = 0.001). The CYP2B6*6 and CYP3A5*3 alleles had no effect on the plasma concentrations of tramadol and its demethylated metabolites. The serum IL-6 and CRP levels were inversely correlated with the plasma concentration ratios of N-desmethyltramadol to tramadol and of N,O-didesmethyltramadol to O-desmethyltramadol. The serum IL-6 level was associated with the treatment duration of oral tramadol. The CYP2D6 genotype but not the CYP2B6 and CYP3A5 genotypes affected the plasma concentrations of O- and N-desmethyltramadol through alteration of the tramadol metabolic pathway. The serum IL-6 level was associated with N-demethylation activity and tramadol tolerability.

CanVar: A resource for sharing germline variation in cancer patients

The advent of high-throughput sequencing has accelerated our ability to discover genes predisposing to disease and is transforming clinical genomic sequencing. In both contexts knowledge of the spectrum and frequency of genetic variation in the general population and in disease cohorts is vital to the interpretation of sequencing data. While population level data is becoming increasingly available from publicly accessible sources, as exemplified by The Exome Aggregation Consortium (ExAC), the availability of large-scale disease-specific frequency information is limited. These data are of particular importance to contextualise findings from clinical mutation screens and small gene discovery projects. This is especially true for cancer, which is typified by a number of hereditary predisposition syndromes. Although mutation frequencies in tumours are available from resources such as Cosmic and The Cancer Genome Atlas, a similar facility for germline variation is lacking. Here we present the Cancer Variation Resource (CanVar) an online database which has been developed using the ExAC framework to provide open access to germline variant frequency data from the sequenced exomes of cancer patients. In its first release, CanVar catalogues the exomes of 1,006 familial early-onset colorectal cancer (CRC) patients sequenced at The Institute of Cancer Research. It is anticipated that CanVar will host data for additional cancers, providing a resource for others studying cancer predisposition and an example of how the research community can utilise the ExAC framework to share sequencing data.

CanVar: A resource for sharing germline variation in cancer patients.

The advent of high-throughput sequencing has accelerated our ability to discover genes predisposing to disease and is transforming clinical genomic sequencing. In both contexts knowledge of the spectrum and frequency of genetic variation in the general population and in disease cohorts is vital to the interpretation of sequencing data. While population level data is becoming increasingly available from publicly accessible sources, as exemplified by The Exome Aggregation Consortium (ExAC), the availability of large-scale disease-specific frequency information is limited. These data are of particular importance to contextualise findings from clinical mutation screens and small gene discovery projects. This is especially true for cancer, which is typified by a number of hereditary predisposition syndromes. Although mutation frequencies in tumours are available from resources such as Cosmic and The Cancer Genome Atlas, a similar facility for germline variation is lacking. Here we present the Cancer Variation Resource (CanVar) an online database which has been developed using the ExAC framework to provide open access to germline variant frequency data from the sequenced exomes of cancer patients. In its first release, CanVar catalogues the exomes of 1,006 familial early-onset colorectal cancer (CRC) patients sequenced at The Institute of Cancer Research. It is anticipated that CanVar will host data for additional cancers, providing a resource for others studying cancer predisposition and an example of how the research community can utilise the ExAC framework to share sequencing data.

Pharmacokinetic variations in cancer patients with liver dysfunction: applications and challenges of pharmacometabolomics.

In cancer patients, pharmacokinetic variations between individuals and within individuals due to impairments in organs' function and other reasons such as genetic polymorphisms represent a major problem in disease management, which can result in unpredictable toxicity and variable antineoplastic effects. Addressing pharmacokinetic variations in cancer patients with liver dysfunction and their implications on anticancer and analgesic drugs, in addition to the use of advanced analytical techniques such as metabolomics and pharmacometabolomics, to monitor altered kinetic and discover metabolic biomarkers during therapeutic intervention will help in understanding and reducing pharmacokinetic variations of drugs in cancer patients as a step forward towards personalised medicine. Reviewing published literature addressing and/or related to complications resulting from altered pharmacokinetics (PKs) in cancer patients with liver dysfunction, anticancer and analgesic drugs, evaluating recent advances of pharmacokinetic detection using metabolomics/pharmacometabolomics and the challenges that are currently facing these techniques. The current situation presents a pressing need to reduce pharmacokinetic variations of drugs in cancer patients. Although most of the omics technologies are not entirely focussed on the study of pharmacokinetic variations and some studies are met with uncertainty, the use of pharmacometabolomics combined with other omics technology such as pharmacogenomics can provide clues to personalised cancer treatments by providing useful information about the cancer patient's response to medical interventions via identification of patients' dependent variables, understanding of correlations between individuals and population PKs, and therapy outcomes to achieve optimum therapeutic effects with minimum toxicity. We also propose an approach for PKs' evaluation using pharmacometabolomics.

Ethnic variation in cancer patients’ ratings of information provision, communication and overall care

ABSTRACTObjective. Ethnic inequalities in cancer patient experience exist but variation within broad ethnic categories is under-explored. This study aimed to describe variation by ethnic sub-category in experiences of information provision and communication (key domains of patient experience) using National Cancer Patient Experience Survey (NCPES) data.Design. The NCPES 2012–2013 contained responses from 68,737 cancer patients treated at 155 NHS Trusts in England. Multivariate logistic regression was used to investigate associations between ethnicity and patients’ ratings of overall care, information provision and communication.Results. Variation by and within broad ethnic categories was evident. Non-White patients (particularly Asian patients (ORadj:0.78; 95%CI:0.67-0.90, p=0.001)) were less likely than White patients to receive an understandable explanation of treatment side effects. Among Asian patients, those of Bangladeshi ethnicity were least likely to receive an understandable explanation.Conclusions. Effective communication and information provision are important to ensure patients are well informed, receive the best possible care and have a positive patient experience. However, ethnic inequalities exist in cancer patients’ experiences of information provision and communication with variation evident both between and within broad ethnic categories. Further work to understand the causes of this variation is required to address ethnic inequalities at practice and policy level.

Variations of blood glucose in cancer patients during chemotherapy.

The aim of this study was to analyze the blood glucose (BG) variations in cancer patients during chemotherapy according to tumor types and chemotherapeutic regimens. Patients were examined from the Department of Medical Oncology of Cancer Hospital and Institute, Chinese Academy Medical Sciences from January 2012 to December 2014. The patients' ages, genders, body mass index, associated disease history, and corresponding BG values were recorded. Among these 2029 patients, 331 (16.3%) patients encountered high BG during chemotherapy except diabetic patients. Of these patients, 208 (62.8%) were males, and 123 (37.2%) were females, with age ranged from 17 to 84 years. The 331 cases included 23 tumor types and 77 regimens. Totally, BG values increased up to 7.4 ± 1.3 mmol/L during chemotherapy. No previous studies in the literature have examined systematically so numerous cases of hyperglycemia during chemotherapy. This study has pointed out possible high-risk chemotherapeutic regimens and tumor types, which should be paid attention to prevent the occurrence of hyperglycemia.

Evaluation of the germline single nucleotide polymorphism rs583522 in the TNFAIP3 gene as a prognostic marker in esophageal cancer

Most esophageal cancer patients die because of disease relapse, hence an accurate prognosis of disease relapse and survival is essential. Genetic variations in cancer patients may serve as important indicators. Three genotypes (GG, AG, and AA) are displayed by the single nucleotide polymorphism (SNP) rs583522, which maps to the TNFAIP3 gene on chromosome 6. Evaluation of the potential prognostic value of the TNFAIP3-SNP in esophageal cancer (EC) was the aim of this study. A total of 158 patients underwent complete surgical resection of the esophagus for EC. None of them received any neoadjuvant or adjuvant treatment. Peripheral blood was sampled, and genomic DNA was extracted from leukocytes before each operation. Clinicopathologic parameters, tumor cell dissemination in bone marrow, and clinical outcome were correlated with the TNFAIP3-SNP. A-allele carriers showed advanced tumor stages compared with those of homozygous G-allele carriers (P<0.001). Patients with an A-allele genotype (AA or AG) were significantly more likely to experience a relapse (P=0.003). Survival analysis (log-rank test) revealed a significant difference in overall survival between the three groups (P=0.039); however, none of the genotypes was identified as a disease stage-independent prognostic marker. In conclusion, TNFAIP3-SNP stratifies patients into different risk groups; however, it could not be identified as an independent prognostic marker.

Ethnic variation in patients' ratings of communication: analysis of National Cancer Patient Experience Survey data

BackgroundEthnic inequalities in cancer patient experience are known to exist; however, variation by ethnic subcategory is not well-explored. Information provision and communication, key domains of patient experience, are also likely to vary by ethnic subcategory, but there have been few detailed analyses to date. The aim of this study was to identify and quantify ethnic variation in cancer patients' experiences of information provision and communication through analysis of data by ethnic categories and subcategories. MethodsThe National Cancer Patient Experience Survey 2012–13 was sent to all adult cancer patients treated in a National Health Service (NHS) hospital from Sept 1, 2012, to Nov 31, 2012. The publically available dataset contained responses to 70 multiple-choice questions and associated demographic information for 68 737 cancer patients from 155 NHS trusts. In this secondary analysis, multivariate logistic regression was used to investigate associations between ethnicity and patients' ratings of overall care, information provision, and communication as measured by 24 questions. FindingsPatients' ratings of communication and information provision varied greatly by ethnicity. For example, non-white patients, in particular Asian patients, were less likely than white patients to receive understandable written information about treatment side-effects (adjusted odds ratio 0·60, 95% CI 0·51–0·70; p<0·0001), and Bangladeshi patients were the least likely within the Asian category to receive such information (0·37, 0·20–0·70; p=0·002). Similarly, non-white patients, in particular Asian patients, were less likely to receive understandable answers to important questions from doctors (0·49, 0·41–0·58; p<0·0001), and Bangladeshi patients were the least likely within the Asian category (0·12, 0·06–0·25; p<0·0001). InterpretationEffective communication and information provision are key aspects of the patient experience, and are very important to ensure that all patients are well informed and receive the best possible patient care. Ethnic inequalities, such as those identified here, should be addressed at both practice and policy level. Health-care professionals should be aware of the inequalities that exist and of their personal ethnic bias. Cultural and racial awareness training would help them to tailor their consultation to the cultural and linguistic needs of their patients. Future policy should be guided by ethnically diverse patient focus groups, and further work should aim to understand causes of ethnic variation in ratings of communication and information provision. FundingHW and LM-L are supported by the National Institute for Health Research Imperial College Healthcare NHS Trust Biomedical Research Centre and Imperial College Healthcare Charity.

An A/C germline single-nucleotide polymorphism in the TNFAIP3 gene is associated with advanced disease stage and survival in only surgically treated esophageal cancer.

Prognostication of disease relapse and survival is essential for cancer patients and genetic variations in cancer patients may serve as important indicators. A single-nucleotide polymorphism (SNP) mapping to the tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) gene at position 138241110 displays three genotypes (AA, AC and CC). The aim of this study was to evaluate the potential prognostic value of the TNFAIP3-SNP in esophageal cancer (EC). Genomic DNA was extracted from peripheral blood leukocytes of 173 patients who underwent complete surgical resection for EC and did not receive any neoadjuvant or adjuvant therapy. For SNP detection, a 260- bp fragment was PCR amplified, purified and sequenced with tested primers. The product was analyzed by automatic DNA sequencer.The TNFAIP3 genotypes were correlated with clinico-pathological parameters, tumor cell dissemination in bone marrow and clinical outcome. The C-allele carrier presented with higher disease stage (P<0.001). This was predominantly because of the presence of lymph node metastasis (P<0.001). The recurrence rate was higher in C-allele carriers (AC and CC genotype; P=0.004). Kaplan-Meier plots for disease-free (P=0.017) and overall survival (P<0.001) displayed a gene dosage-associated outcome with AA genotype patients presenting the longest and CC genotype patients the poorest survival. In disease stage-adjusted multivariate analysis the TNFAIP3-SNP was identified as an independent prognostic factor for survival (hazard ratio 1.9; P=0.008). The TNFAIP3-SNP allows risk stratification of EC patients and may be a useful tool to identify patients eligible for multimodal therapy concepts.

Mitochondrial D-Loop Polymorphism and Microsatellite Instability in Prostate Cancer and Benign Hyperplasia Patients

In this study mitochondrial D-Loop variations in Iranian prostate cancer and benign prostatic hyperplasia (BPH) patients were investigated. Tumour samples and corresponding non-cancerous prostate tissue from 40 prostate cancer patients and 40 age-matched BPH patients were collected. The entire mtD-loop region (16024-576) was amplified using the PCR method and products were gel-purified and subjected to direct nucleotide sequencing. A total of 129 variations were found, the most frequent being 263A-G and 310T-C among both BPH and prostate cancer patients. Variation of 309 C-T was significantly more frequent in prostate cancer patients (P value<0.05). Four novel variations were observed on comparison with the MITOMAP database. Novel variations were np16154delT, np366G-A, np389G-A and 56insT. There was no correspondence between the different variations and the age of subjects. Considering that D-loop variations were frequent in both BPH and prostate cancer patients in our study, the fact that both groups had high average age can be a possible contributing factor. D-loop polymorphisms and microsatellite instability can influence cell physiology and result in a benign or malignant phenotype. Significantly higher frequency of 309 C-T variation in cancer patients is a notable finding and must be a focus of attention in future studies.

The GNAS1 T393C single nucleotide polymorphism predicts the natural postoperative course of complete resected esophageal cancer

Genetic variations in cancer patients may serve as important prognostic indicators of clinical outcome. The GNAS1 T393C single nucleotide polymorphism (SNP) diversely correlates with the clinical outcome in cancer. The aim of this study was to evaluate the potential prognostic value of T393C-SNP in complete resected only surgically treated esophageal cancer (EC). Genomic DNA was extracted from peripheral blood leucocytes of 190 patients who underwent only complete surgical resection for EC. T393C-SNP was correlated with clinic-pathological parameters, tumor cell dissemination in bone marrow (DTC) and clinical outcome. T-allele carriers had more advanced disease due to presence of lymph node metastasis (P < 0.0001) and DTC (P = 0.01) and higher recurrence rate (P = 0.01) compared to CC genotype. The disease-free (P < 0.001) and overall survival (P < 0.001) was better in CC compared to TT and TC patients. In the multivariate Cox regression disease-stage adjusted analysis the T393C-SNP was identified as a strong independent prognostic factor for recurrence (hazard ratio 1.8, P = 0.01) and survival (hazard ratio 2.5, P < 0.001) in EC patients. Determination of T393C-SNP preoperatively will allow allocation of EC patients into different risk profiles which may help to stratify patients eligible for neoadjuvant and or adjuvant therapy.

DNA profiling by array comparative genomic hybridization (CGH) of peripheral blood mononuclear cells (PBMC) and tumor tissue cell in non-small cell lung cancer (NSCLC)

Lung tumor cell DNA copy number alteration (CNA) was expected to display specific patterns such as a large-scale amplification or deletion of chromosomal arms, as previously published data have reported. Peripheral blood mononuclear cell (PBMC) CNA however, was expected to show normal variations in cancer patients as well as healthy individuals, and has thus been used as normal control DNA samples in various published studies. We performed array CGH to measure and compare genetic changes in terms of the CNA of PBMC samples as well as DNA isolated from tumor tissue samples, obtained from 24 non-small cell lung cancer patients. Contradictory to expectations, our studies showed that the PBMC CNA also showed chromosomal variant regions. The list included well-known tumor-associated NTRK1, FGF8, TP53, and TGFbeta1 genes and potentially novel oncogenes such as THPO (3q27.1), JMJD1B, and EGR1 (5q31.2), which was investigated in this study. The results of this study highlighted the connection between PBMC and tumor cell genomic DNA in lung cancer patients. However, the application of these studies to cancer prognosis may pose a challenge due to the large amount of information contained in genetic predisposition and family history that has to be processed for useful downstream clinical applications.