Genetic factors affecting patient responses to pancreatic cancer treatment.
Ontology highlight
ABSTRACT:
SUBMITTER: Fotopoulos G
PROVIDER: S-EPMC5049553 | biostudies-literature | 2016 Oct-Dec
REPOSITORIES: biostudies-literature
Publications
Genetic factors affecting patient responses to pancreatic cancer treatment.
Fotopoulos George G Syrigos Konstantinos K Saif Muhammad Wasif MW
Annals of gastroenterology 20160610 4
Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pha ...[more]
Similar Datasets
Project description:Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17, p = 3.03 × 10-6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.
| S-EPMC8435735 | biostudies-literature
Project description:ObjectiveTo identify patient factors associated with whether women who screened positive for high-risk human papillomavirus (hrHPV) successfully accessed treatment in a cervical cancer prevention program in Kenya.MethodsA prospective cohort study was conducted as part of a trial of implementation strategies for hrHPV-based cervical cancer screening in western Kenya from January 2018 to February 2019. In this larger trial, women underwent hrHPV testing during community health campaigns (CHCs), and hrHPV+ women were referred to government facilities for cryotherapy. For this analysis, we looked at rates of and predictors of presenting for treatment and presenting within 30 days of receiving positive hrHPV results ("timely" presentation). Data came from questionnaires completed at the time of screening and treatment. Multivariable logistic regression was used to identify factors associated with each outcome.ResultsOf the 505 hrHPV+ women, 266 (53%) presented for treatment. Cryotherapy was performed in 236 (89%) of the women who presented, while 30 (11%) were not treated: 15 (6%) due to gas outage, six (2%) due to pregnancy, five (2%) due to concern for cervical cancer, and four (2%) due to an unknown or other reason. After adjusting for other factors in the multivariable analysis, higher education level and missing work to come to the CHC were associated with presenting for treatment. Variables that were associated with increased likelihood of timely presentation were missing work to come to the CHC, absence of depressive symptoms, told by someone important to come to the CHC, and shorter distance to the treatment site.ConclusionThe majority of hrHPV+ women who did not get treated were lost at the stage of decision-making or accessing treatment, with a small number encountering barriers at the treatment sites. Patient education and financial support are potential areas for intervention to increase rates of hrHPV+ women seeking treatment.
| S-EPMC6750649 | biostudies-literature
Project description:BackgroundRehabilitation of the edentulous patients has always been a challenge. The success of conventional complete denture therapy might be affected by several factors such as patients' age, personality, previous denture wearing experience, expectations, aesthetics, residual ridge form and anatomy, denture quality, the method of its construction, dentist experience, and dentist-patient relations.ObjectivesThe aim of this study was to compare patient satisfaction with complete dentures provided by fourth and fifth year dental students and prosthodontists with a minimum of 5 years' experience at the University of Jordan Hospital 8 weeks after insertion.MethodsQuestionnaires were distributed to a total of 60 completely edentulous patients who received complete maxillary and mandibular dentures. Besides demographic questions, the questionnaire included questions that probed the patient's satisfaction with his maxillary and mandibular dentures in general using two types of scales.ResultsResults indicated that dentist experience does not affect patients' satisfaction with their complete dentures. Our results also indicated that patients who had previous dentures could adapt more easily and were generally more satisfied with their newly inserted dentures especially with regard to their chewing ability and comfort with their mandibular dentures. Gender also influenced patient satisfaction with complete dentures especially the part related to psychological and social disability.ConclusionsResults of this study will help in further understanding factors influencing patient satisfaction with their complete dentures.
| S-EPMC9012642 | biostudies-literature
Project description:Primary cutaneous aspergillosis (PCA) is an uncommon infection of the skin. There is a paucity of organized literature regarding this entity in regard to patient characteristics, associated Aspergillus species, and treatment modalities on outcome (disease recurrence, disease dissemination, and mortality).We reviewed all published reports of PCA from 1967 to 2015. Cases were deemed eligible if they included the following: patient baseline characteristics (age, sex, underlying condition), evidence of proven or probable PCA, primary treatment strategy, and outcome.We identified 130 eligible cases reported from 1967 to 2015. The patients were predominantly male (63.8%) with a mean age of 30.4?±?22.1 years. Rates of PCA recurrence, dissemination, and mortality were 10.8%, 18.5%, and 31.5%, respectively. In half of the cases, there was an association with a foreign body. Seven different Aspergillus species were reported to cause PCA. Systemic antifungal therapy without surgery was the most common form of therapy (60% of cases). Disease dissemination was more common in patients with underlying systemic conditions and occurred on average 41.4 days after PCA diagnosis (range of 3-120 days). In a multivariate linear regression model of mortality including only patients with immunosuppressive conditions, dissemination and human immunodeficiency virus/acquired immune deficiency syndrome were statistically significantly associated with increased mortality.Nearly one-third of patients with PCA die with the disease. Dissemination and host status are critical in patient outcome.
| S-EPMC4937894 | biostudies-other
Project description:Veterans enrolled in the Veterans Affairs (VA) health care system gained greater access to non-VA care beginning in 2014. We examined hospital and Veteran characteristics associated with hospital choice. We conducted a longitudinal study of elective hospitalizations 2011 to 2017 in 11 states and modeled patients' choice of VA hospital, large non-VA hospital, or small non-VA hospital in conditional logit models. Patients had higher odds of choosing a hospital with an academic affiliation, better patient experience rating, location closer to them, and a more common hospital type. Patients who were male, racial/ethnic minorities, had higher VA enrollment priority, and had a mental health comorbidity were more likely than other patients to choose a VA hospital than a non-VA hospital. Our findings suggest that patients respond to certain hospital attributes. VA hospitals may need to maintain or achieve high levels of quality and patient experience to attract or retain patients in the future.
| S-EPMC10842609 | biostudies-literature
Project description:IntroductionCancer treatment planning in older adults is complex and requires careful balancing of survival, quality of life benefits, and risk of treatment-related morbidity and toxicity. As a result, treatment selection in this cohort tends to differ from that for younger patients. However, there are very few studies describing cancer treatment patterns in older cohorts.MethodsWe used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Cancer Treatment Substudy (ACTS) to describe cancer treatment patterns in older adults. We used a multivariate logistic regression model to identify factors affecting receipt of treatment.ResultsOf 1893 eligible Australian and United States (US) participants with incident cancer, 1569 (81%) received some form of cancer treatment. Non-metastatic breast cancers most frequently received treatment (98%), while haematological malignancy received the lowest rates of treatment (60%). Factors associated with not receiving treatment were older age (OR 0.94, 95% CI 0.91-0.96), residence in the US (OR 0.34, 95% CI 0.22-0.54), smoking (OR 0.57, 95% CI 0.40-0.81), and diabetes (OR 0.56, 95% CI 0.39-0.80). After adjustment for treatment patterns in sex-specific cancers, sex did not impact receipt of treatment.ConclusionsThis study is one of the first describing cancer treatment patterns and factors affecting receipt of treatment across common cancer types in older adults. We found that most older adults with cancer received some form of cancer treatment, typically surgery or systemic therapy, although this varied by factors such as cancer type, age, sex, and country of residence.
| S-EPMC9953887 | biostudies-literature
Project description:BackgroundDespite the proven benefits of exercise rehabilitation for numerous health conditions, musculoskeletal injuries and recovery from surgery, patient adherence to such programs is reported to often be less than 35%. Increasing patient engagement therefore has the potential to improve patient health outcomes, benefiting the patient, their carers and the services that support them. The aims of this review were to identify the factors that contribute to 'patient' engagement in prescribed exercise rehabilitation using the COM-B (capability, opportunity, motivation-behaviour) framework of behavioural analysis.MethodsFive electronic databases (PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov) were searched. 'COM-B' was the key word searched for specifically within titles and abstracts, combined with either 'physical activity' OR 'exercise' included using the 'AND' operation. Records were then filtered and excluded following full-text screening based on the predetermined eligibility criteria.ResultsTwenty studies were included in the review. The main COM-B themes highlighted for improving patient engagement were: capability-improving patient knowledge and cognitive skills for behavioural regulation, such as 'action planning' and 'action control', which could also benefit time-management; opportunity-a balanced life situation that enabled time to be devoted to the exercise program, social support, easily accessible and affordable resources and services; and motivation-increasing patient levels of self-efficacy and autonomous motivation, which were noted to be influenced by levels of perceived 'capability', additionally 'motivation' was noted to be influenced by patients perceiving the benefits of the exercise, and adherence to the program was promoted by 'goal-setting'. Other issues in the 'capability' domain included a fear and/or dislike of exercise.ConclusionPatient engagement behavior has been shown to be influenced by both external (opportunity) and intrapersonal variables (capability and motivation). Those prescribing exercises within a rehabilitation program need to discuss these factors with their patients and co-design the exercise rehabilitation program in partnership with the patient, since this is likely to improve patient engagement, and thereby result in superior health outcomes. Furthermore, these factors need to be a consideration in clinical trials, if the findings from such trials are to translate into mainstream healthcare settings.
| S-EPMC8819209 | biostudies-literature
Project description:ObjectiveCancer outcomes vary between and within countries with patients from deprived backgrounds known to have inferior survival. The authors set out to explore the effect of deprivation in relation to the accessibility of hospitals offering diagnostic and therapeutic services on stage at presentation and receipt of treatment.DesignAnalysis of a Cancer Registry Database. Data included stage and treatment details from the first 6 months. The socioeconomic status of the immediate area of residence and the travel time from home to hospital was derived from the postcode.SettingPopulation-based study of patients resident in a large area in the north of England.Participants39?619 patients with colorectal cancer diagnosed between 1994 and 2002.Outcomes measuredStage of diagnosis and receipt of treatment in relation to deprivation and distance from hospital.ResultsPatients in the most deprived quartile were significantly more likely to be diagnosed at stage 4 for rectal cancer (OR 1.516, p<0.05) but less so for colonic cancer. There was a trend for both sites for patients in the most deprived quartile to be less likely to receive chemotherapy for stage 4 disease. Patients with colonic cancer were very significantly less likely to receive any treatment if they came from any but the most affluent area (ORs 0.639, 0.603 and 0.544 in increasingly deprived quartiles), this may have been exacerbated if the hospital was distant from their residence (OR for forth quartile for both travel and deprivation 0.731, not significant). The effect was less for rectal cancer and no effect of distance was seen.ConclusionsResiding in a deprived area is associated with tendencies to higher stage at diagnosis and especially in the case of colonic cancer to reduced receipt of treatment. These observations are consistent with other findings and indicate that access to diagnosis requires further investigation.
| S-EPMC3341592 | biostudies-literature
Project description:To assess (1) the variance of plasma clozapine levels; (2) the relative importance of sex, smoking habits, weight, age, and specific genetic variants of cytochrome P450 1A2 (CYP1A2), uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), and multidrug resistance protein 1 (MDR1) on plasma levels of clozapine; and (3) the relation between plasma clozapine levels, fasting glucose levels, and waist circumference. There were 113 patients on clozapine treatment recruited from psychosis outpatient clinics in Stockholm County, Sweden. Patients had genotype testing for single nucleotide polymorphisms: 2 in MDR1, 3 in CYP1A2, and 1 in UGT1A4. Multiple and logistic regression were used to analyze the relations. There was a wide variation in plasma concentrations of clozapine (mean = 1,615 nmol/L, SD = 1,354 nmol/L), with 37% of the samples within therapeutic range (1,100-2,100 nmol/L). Smokers had significantly lower plasma clozapine concentrations than nonsmokers (P ≤ .03). There was a significant association between the rs762551 A allele of CYP1A2 and lower plasma clozapine concentration (P ≤ .05). Increased fasting glucose level was 3.7-fold more frequent in CC and CA genotypes than AA genotype (odds ratio = 0.27; 95% confidence interval, 0.10-0.72). There was no significant relation between higher fasting glucose levels, larger waist circumference, and higher clozapine levels. It is difficult to predict plasma clozapine concentration, even when known individual and genetic factors are considered. Therefore, therapeutic drug monitoring is recommended in patients who are treated with clozapine.
| S-EPMC4468884 | biostudies-literature
Project description:BackgroundPancreatic cancer is a rapidly fatal disease with gemcitabine remaining the first-line therapy. We performed a genotype-phenotype association study to identify biomarkers for predicting gemcitabine treatment outcome.Materials and methodsWe selected the top 200 single nucleotide polymorphisms (SNPs) identified from our previous genome-wide association study to associate with overall survival using 400 patients treated with/or without gemcitabine, followed by imputation analysis for regions around the identified SNPs and a replication study using an additional 537 patients by the TaqMan genotyping assay. Functional validation was performed using quantitative reverse transcription-PCR for gemcitabine-induced expression in genotyped lymphoblastoid cell lines and siRNA knockdown for candidate genes in pancreatic cancer cell lines.ResultsFour SNPs in chromosome 1, 3, 9, and 20 showed an interaction with gemcitabine from the discovery cohort of 400 patients (P<0.01). Subsequently, we selected those four genotyped plus four imputed SNPs for SNP×gemcitabine interaction analysis using the secondary validation cohort. Two imputed SNPs in CDH4 and KRT8P35 showed a trend in interaction with gemcitabine treatment. The lymphoblastoid cell lines with the variant sequences showed increased CDH4 expression compared with the wild-type cells after gemcitabine exposure. Knockdown of CDH4 significantly desensitized pancreatic cancer cells to gemcitabine cytotoxicity. The CDH4 SNPs that interacted with treatment are more predictive than prognostic.ConclusionWe identified SNPs with gemcitabine-dependent effects on overall survival. CDH4 might contribute to variations in gemcitabine response. These results might help us to better predict gemcitabine response in pancreatic cancer.
| S-EPMC5083195 | biostudies-literature