Dupuytren's disease and the risk of malignant neoplasms.
Ontology highlight
ABSTRACT:
SUBMITTER: Zyluk A
PROVIDER: S-EPMC3973858 | biostudies-literature | 2014 Mar
REPOSITORIES: biostudies-literature
Publications
Dupuytren's disease and the risk of malignant neoplasms.
Zyluk Andrzej A Paszkowska-Szczur Katarzyna K Gupta Satish S Scott Rodney J RJ Lubiński Jan J Dębniak Tadeusz T
Hereditary cancer in clinical practice 20140306 1
The object of this study was the investigation of the risk of occurrence of malignant neoplasms in 508 patients with Dupuytren's disease (DD) and in 2157 of their 1st degree relatives. In the first stage of the study, we evaluated the tumour spectrum as well as the age of the patient at diagnosis of cancers in DD families along with the observed and expected frequencies of malignancies. In the second stage of the study, we examined the distribution of 20 common mutations/polymorphisms in 12 know ...[more]
Similar Datasets
Project description:Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.
| S-EPMC3295744 | biostudies-literature
Project description:An indirect consequence of the improved long-term survival seen in patients with breast cancer (BC) is the increased risk of hematologic malignant neoplasms (HM). This study aimed to analyze the role of postoperative treatment for BC in the development of subsequent HM. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident primary breast cancer between 2007 and 2015, who underwent surgery as first-line treatment for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin's lymphoma or non-Hodgkin's lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Analyses were censored at HM occurrence, death, loss to follow up, or December 2017. The risk of each type of HM was compared according to the initial postoperative treatment of breast cancer. Of a total of 324,056 BC survivors, 15.5% underwent surgery only, 46.7% received radiotherapy after surgery, 4.3% received chemotherapy after surgery, and 33.5% received all three modalities. Overall, 2236 cases of hematologic malignancies occurred. Compared to the surgery alone group, AML was significantly increased after surgery plus radiation (aHR, 1.5; 95% CI, 1.0-2.1), surgery plus chemotherapy (aHR, 2.1; 95% CI, 1.2-3.6) and all modalities (aHR, 3.3; 95% CI, 2.3-4.7). MDS was significantly increased after surgery plus chemotherapy (aHR, 1.7; 95% CI, 1.1-2.5) or after all modalities (aHR, 1.4; 95% CI, 1.1-1.8). HL/NHL were significantly increased only in the radiotherapy and surgery group (aHR, 1.3; 95% CI, 1.0-1.6). A nonsignificant increase of ALL/LL (aHR, 1.8; 95% CI, 0.6-3.5) was noted after chemotherapy and with all three modalities (aHR, 1.4; 95% CI, 0.7-2.8). Our population based study revealed increased risks of various HM associated with postoperative BC treatment. The added benefit of chemotherapy and radiation therapy should take into consideration these long-term complications.
| S-EPMC6827362 | biostudies-literature
Project description:Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study, we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD-associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD.
2013-10-01 | GSE41524 | GEO
Project description:BackgroundThe correlation between smoking and alcohol consumption and the development of Dupuytren's disease (DD) has been acknowledged. However, the definitive causal relationship between these two factors and DD remains elusive. In order to establish a causal connection, we employed the two-sample Mendelian randomization method to evaluate the relationship between smoking and alcohol consumption and DD.MethodsBased on publicly available genome-wide association studies (GWAS), two-sample univariate MR analyses were performed to assess the causal effects of drinks per week, cigarettes per day, smoking initiation, age of initiation, and smoking cessation on DD. We used inverse variance weighted (IVW) to generate the primary results for the MR analysis. Furthermore, we performed sensitivity MR analyses based on various methods to assess the robustness of estimations. Bidirectional MR analyses were used to study the interaction between smoking and alcohol consumption. Multivariate MR analyses were used to obtain independent causal effects of smoking or drinking on DD.ResultsOur two-sample MR, which was predominately based on IVW, revealed a causal relationship between drinks per week and DD (OR = 2.948, 95%CI: 1.746-4.975, P = 5.16E-05). In addition, there is no causal association between cigarettes per day, smoking initiation, age of initiation, smoking cessation and DD. Similar conclusions were reached by other MR methods. The results of the bidirectional MR analyses showed that the causal relationships between age of initiation and drinks per week were robust and significant. Multivariate MR results indicated that the causal effect of alcohol consumption on DD was independent of smoking.ConclusionOur Mendelian Randomization study indicated that there is a causality between drinking alcohol and DD, but no such causality was found between smoking and DD. This is the first study to prove that drinking alcohol could cause DD. This could help people who are trying to prevent DD from happening in the first place.
| S-EPMC10483747 | biostudies-literature
Project description:To evaluate the association of tumor-associated neutrophils (TANs) with malignant progression in intraductal papillary mucinous neoplasms (IPMNs) and to study the cyst fluid from these lesions for biomarkers of the inflammation-carcinogenesis association.There is a strong link between TANs and malignant progression. Inflammatory mediators released by these cells may be a measurable surrogate marker of this progression.We evaluated 78 resected IPMNs (2004-2013). Lesions were divided into the low-risk (low- and intermediate-grade dysplasia: n?=?48) and high-risk (high-grade dysplasia and invasive carcinoma: n?=?30) groups. TANs were assessed and categorized (negative, low, and high). A multiplexed assay was performed to evaluate 87 different cyst fluid proteins, including cyst fluid inflammatory markers (CFIMs), as possible surrogate markers for parenchymal inflammation.Significant positive correlation between grade of dysplasia and TANs was found. High levels of TANs were identified in 2%, 33%, and 89% of the lesions when stratified by grade of dysplasia into low/intermediate-grade dysplasia, high-grade dysplasia, and invasive carcinoma, respectively (P?<?0.001). Higher grades of dysplasia were also found to have positive correlation with 29 of the measured proteins, of which 23 (79%) were CFIMs. Higher levels of TANs correlated with higher levels of 18 CFIMs, of which 16 (89%) were also found to be associated with higher grades of dysplasia.In this study, TANs were strongly associated with malignant progression in IPMNs. Measurement of CFIMs may be a surrogate marker for IPMN progression and allow for the identification of high-risk disease.
| S-EPMC4643387 | biostudies-literature
Project description:Importance:The cancer disease label may lead to overtreatment of low-risk malignant neoplasms owing to a patient's emotional response or misunderstanding of prognosis. Decision making should be driven by risks and benefits of treatment and prognosis rather than disease label. Objective:To determine whether disease label plays a role in patient decision making in the setting of low-risk malignant neoplasms and to determine how the magnitude of the disease-label effect compares with preferences for treatment and prognosis. Design, Setting, and Participants:A discrete choice experiment conducted using an online survey of 1314 US residents in which participants indicated their preferences between a series of 2 hypothetical vignettes describing the incidental discovery of a small thyroid lesion. Vignettes varied on 3 attributes: disease label (cancer, tumor, or nodule); treatment (active surveillance or hemithyroidectomy); and risk of progression or recurrence (0%, 1%, 2%, or 5%). The independent associations of each attribute with likelihood of vignette selection was estimated with a Bayesian mixed logit model. Main Outcomes and Measures:The preference weight of the cancer disease label was compared with preference weights for other attributes. Results:In 1068 predominantly healthy respondents (605 women and 463 men) with a median age of 35 years (range, 18-78 years), the cancer disease label played a considerable role in respondent decision making independent of treatment offered and risk of progression or recurrence. Participants accepted a 4-percentage-point increase in risk of progression or recurrence (from 1% to 5%) to avoid labeling their disease as cancer in favor of nodule (marginal rate of substitution [MRS], 1.0; 95% credible interval [CrI], 0.9-1.1). Preference for the nodule label instead of cancer was similar in magnitude to the preference for active surveillance over surgery (MRS, 1.0; 95% CrI, 0.9-1.1). Conclusions and Relevance:Disease label plays a role in patient preference independent of treatment risks or prognosis. Raising the threshold for biopsy or removing the word cancer from the disease label may mitigate patient preference for aggressive treatment of low-risk lesions. Health care professionals should emphasize treatment risks and benefits and natural disease history when supporting treatment decisions for potentially innocuous epithelial malignant neoplasms.
| S-EPMC6567830 | biostudies-literature
Project description:PURPOSE: Dupuytren's disease (DD) is characterized by fibroblastic proliferation of the palmar fascia, often leading to flexion contracture in the hand. Although there is a strong genetic component the genome-wide expression of novel genes is not known. The purpose of this study was to use DNA microarray technology to identify upregulated genes in DD. METHODS: Human tissue samples were harvested from 3 patient sources: DD cord tissue (n = 20), normal-appearing adjacent control fascia (n = 15), and palmar fascia from patients having carpal tunnel release (n = 15). DNA microarray analysis was performed on amplified sample RNA. Novel genes were compared with known gene functions. A candidate gene of interest was studied further by using immunohistochemistry on DD tissue samples and controls. : Several novel genes not described previously in the study of DD were upregulated significantly, including MafB, collagen type V, alpha-2 (COL5A2), collagen type VIII, alpha-1 (COL8A1), contactin I (CNTN1), and leucine-rich repeat containing 17 (LRRC17). These upregulated genes were compared with their known gene-expression profiles in other tissues and their purported functions. MafB was found to be of particular interest because of its prominent role in tissue development and cellular differentiation. MafB immunohistochemistry showed positive staining in 50% of the DD specimens but complete absence of MafB in all control tissues (adjacent control fascia, carpal tunnel fascia). Co-localization experiments with MafB and alpha-smooth muscle actin showed staining properties in similar regions but these 2 proteins were not confined solely to the same cells. CONCLUSIONS: Microarray analysis of DD tissue has identified significant upregulated gene expression of MafB. MafB protein also is found in Dupuytren's cords but not in control fascia. Co-localization data suggest that the association of MafB with DD is not related exclusively to myofibroblast proliferation. Because of its role in fibroblastic transformation in other models MafB and its relationship to the pathogenesis of DD deserves further study. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2006-03-15 | GSE4457 | GEO
Project description:Dupuytren's disease (DD) is characterized by nodular fibroblastic proliferation of the palmar fascia leading to contracture of the hand. We performed a cDNA microarray analysis of DD palmar cord tissue. Normal-appearing palmar fascia adjacent to the diseased cord from the same patient and palmar fascia from patients undergoing carpal tunnel release were used as controls. A type II microarray experiment was used on amplified sample RNA. Samples were hybridized to arrays containing 42,000 gene elements. Array data was analyzed with the on-line software from the Stanford Microarray Database. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Type: disease_state_design Series_overall_design: Computed Keywords: other
2006-05-19 | GSE2688 | GEO
Project description:Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study, we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD-associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD. Four exon arrays of DD primary fibroblasts derived from fibrotic tissue were compared to fibroblasts derived from skin punch biopsies from individuals who did not show DD symptoms.
2013-10-01 | E-GEOD-41524 | biostudies-arrayexpress
Project description:AimPrevious investigations have shown that end-stage renal disease (ESRD) is associated with an increased risk of malignancies. The aim of this study was to explore the association between ESRD in patients undergoing maintenance haemodialysis (HD) and the incidence of malignancies according to age.MethodsWe analysed a nationwide cohort retrieved from Taiwan's National Health Insurance Research Database to study the incidence of malignancies in patients who were and were not receiving HD. One million beneficiaries were randomly selected and followed from 2005 to 2013. Of these 1?000?000 patients, 3055 developed ESRD and commenced maintenance HD during this period. For each HD patient, four age-, gender- and diabetes-matched controls were selected from the database (n?=?12?220). We further stratified the patients according to age. The study endpoint was the occurrence of malignancy.ResultsThe incidence rates of malignancy were 6.8% and 4.9% in the HD and control groups, respectively. Competing risk regression analysis indicated that age, HD, male gender and diabetes were associated with an increased risk of malignancy. When further stratified according to age, the odds ratios of developing cancer were 5.8, 1.9, 1.9 and 1.5 among the HD patients aged <40?years, 40-49?years, 50-59?years and 60-69?years, respectively.ConclusionThe patients with ESRD who received HD had a significantly higher cumulative risk of malignancy, especially those with a young age. Therefore, specialized cancer screening protocols for young HD patients might help to prolong their lifespan.
| S-EPMC6849784 | biostudies-literature