scholarly journals Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6515-6520 ◽  
Author(s):  
Henrik Frederiksen ◽  
Dóra Körmendiné Farkas ◽  
Christian Fynbo Christiansen ◽  
Hans Carl Hasselbalch ◽  
Henrik Toft Sørensen
Keyword(s):  
Cancer Risk ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Hematologic Malignancies ◽  
Population Based ◽  
National Registry ◽  
Standardized Incidence Ratio ◽  
Chronic Myeloproliferative Neoplasms ◽  
Increased Risk ◽  
Subsequent Cancer

Abstract Patients with chronic myeloproliferative neoplasms, including essential thrombocythemia (ET), polycythemia vera (PV), and chronic myeloid leukemia (CML), are at increased risk of new hematologic malignancies, but their risk of nonhematologic malignancies remains unknown. In the present study, we assessed the risk of both types of malignancies after an ET, PV, or CML diagnosis. We linked 2 population-based nationwide registries, the Danish National Registry of Patients, covering all Danish hospitals and the Danish Cancer Registry, and assessed subsequent cancer risk in a cohort of all 7229 patients diagnosed with a chronic myeloproliferative neoplasm during 1977-2008. We compared the incidence of subsequent cancer in this cohort with that expected on the basis of cancer incidence in the general population (standardized incidence ratio). Overall, ET, PV, and CML patients were at increased risk of developing both new hematologic and nonhematologic cancers. The standardized incidence ratio for developing a nonhematologic cancer was 1.2 (95% confidence interval [95% CI]): 1.0-1.4) for patients with ET, 1.4 (95% CI: 1.3-1.5) for patients with PV, and 1.6 (95% CI: 1.3-2.0) for patients with CML. We conclude that patients with chronic myeloproliferative neoplasms are at increased risk of developing a new malignant disease.

scholarly journals THE JAK2V617F POINT MUTATION INCREASES THE OSTEOCLAST FORMING ABILITY OF MONOCYTES IN PATIENTS WITH CHRONIC MYELOPROLIFERATIVE NEOPLASMS AND MAKES THEIR OSTEOCLASTS MORE SUSCEPTIBLE TO JAK2 INHIBITION

2018 ◽  
Vol 10 ◽  
pp. e2018058
Author(s):  
Emmanouil Spanoudakis ◽  
Menelaos Papoutselis ◽  
Ioanna Bazntiara ◽  
Eleftheria Lamprianidou ◽  
Xrisa Kordella ◽  
...  
Keyword(s):  
Point Mutation ◽  
Genomic Dna ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Cellular Level ◽  
Hemopoietic Stem Cell ◽  
Jak2 Inhibitor ◽  
Chronic Myeloproliferative Neoplasms ◽  
Cell Niche ◽  
Jak2 Inhibition

JAK2V617F is a gain of function point mutation that occurs in Myeloproliferative Neoplasm (MPN) patients and deranges their hemopoiesis at cellular level. We speculate that hyperfunctioning JAK2 can modify osteoclast (OCL) homeostasis in MPN patients. We studied 18 newly diagnosed MPN patients and four age-matched normal donors (ND). Osteoclast forming assays started from selected monocytes also and under titrated concentrations of the JAK2 Inhibitor AG-490 (Tyrphostin). Genomic DNA was extracted from the formed osteoclasts, and the JAK2V617F/JAK2WT genomic DNA ratio was calculated. OCLs formed from monocytes derived from heterozygous (Het) for the JAK2V617F mutation MPN patients, were three times more compared to those from JAK2 wild type (WT) MPN patients (p=0,05) and from ND as well (p=0,03). The ratio of JAK2V617F/JAK2WT genomic DNA was increased in OCLs compared to the input monocyte cells showing a survival advantage of the mutated clone. In comparison to ND and JAK2 WT MPN patients, OCLs from patients JAK2V617F (Het) were more susceptible to JAK2 inhibition. These alterations in osteoclast homeostasis, attributed to mutated JAK2, can deregulate the hemopoietic stem cell niche in MPN patients.

Increased risk of cancer in patients with retinal vein occlusion: a 12-year nationwide cohort study

2020 ◽  
pp. bjophthalmol-2020-316947
Author(s):  
Min Seok Kim ◽  
Joon Hee Cho ◽  
Seong Jun Byun ◽  
Chang-Mo Oh ◽  
Kyu Hyung Park ◽  
...  
Keyword(s):  
Retinal Vein Occlusion ◽  
Cox Regression ◽  
Subsequent Development ◽  
Population Based ◽  
Control Group ◽  
Time Varying ◽  
Vein Occlusion ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Subsequent Cancer

AimsTo investigate the association between incident retinal vein occlusion (RVO) and the subsequent development of cancer.MethodsIn this nationwide population-based retrospective study using 2002–2013 National Health Insurance Service database which covers the entire South Korean population, 186 701 incident RVO patients and their 1:1 propensity-score matched controls were included. We defined the fixed cohort from January 1st, 2004 to December 31st, 2013; the cohort included patients who suffered incident RVO after entering the cohort and their matched controls, and excluded patients having any cancer history before entering the cohort. The association of RVO and cancer was assessed by time-varying covariate Cox regression models; Model 1 included RVO as a time-varying covariate, Model 2 included Model 1 plus demographic information and Model 3 included Model 2 and comorbidities.ResultsRVO was associated with an increased risk of subsequent cancer (HR=1.29; 95% CI, 1.26–1.31 in Model 1), which was consistent in Models 2 and 3. The incidence rate of overall cancer during the study period was 25.55 (95% CI, 25.19–25.91) per 1000 person-years in the RVO group and 18.62 (95% CI, 18.46–18.79) per 1000 person-years in the control group. In the subgroup analysis, haematological malignancies showed the highest association with RVO (HR=1.65; 95% CI, 1.49–1.83).ConclusionPatients with RVO have an increased risk of subsequent cancer development even after adjusting for demographic factors and comorbidities. Further study is warranted to elucidate these associations to provide proper recommendations for RVO patients regarding the cancer screening.

scholarly journals Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR–ABL-Negative Myeloproliferative Neoplasm

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1037
Author(s):  
Alessandro Allegra ◽  
Giovanni Pioggia ◽  
Alessandro Tonacci ◽  
Marco Casciaro ◽  
Caterina Musolino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Chronic Inflammation ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Tumor Stage ◽  
Driver Mutations ◽  
Hematopoietic Stem ◽  
Chronic Myeloproliferative Neoplasms ◽  
Inflammatory State

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have recently been revealed to be related to chronic inflammation, oxidative stress, and the accumulation of reactive oxygen species. It has been proposed that MPNs represent a human inflammation model for tumor advancement, in which long-lasting inflammation serves as the driving element from early tumor stage (over polycythemia vera) to the later myelofibrotic cancer stage. It has been theorized that the starting event for acquired stem cell alteration may occur after a chronic inflammation stimulus with consequent myelopoietic drive, producing a genetic stem cell insult. When this occurs, the clone itself constantly produces inflammatory components in the bone marrow; these elements further cause clonal expansion. In BCR–ABL1-negative MPNs, the driver mutations include JAK 2, MPL, and CALR. Transcriptomic studies of hematopoietic stem cells from subjects with driver mutations have demonstrated the upregulation of inflammation-related genes capable of provoking the development of an inflammatory state. The possibility of acting on the inflammatory state as a therapeutic approach in MPNs appears promising, in which an intervention operating on the pathways that control the synthesis of cytokines and oxidative stress could be effective in reducing the possibility of leukemic progression and onset of complications.

Marked Increase in Incident Gynecomastia: A 20-Year National Registry Study, 1998 to 2017

2020 ◽  
Vol 105 (10) ◽  
pp. 3134-3140 ◽  
Author(s):  
Trine Koch ◽  
Elvira V Bräuner ◽  
Alexander S Busch ◽  
Martha Hickey ◽  
Anders Juul
Keyword(s):  
Age Groups ◽  
Population Based ◽  
Incidence Rates ◽  
National Registry ◽  
Registry Study ◽  
Age Related ◽  
Danish Health ◽  
Increased Risk ◽  
National Patient ◽  
First Time

Abstract Context Gynecomastia, the proliferation of mammary glandular tissue in the male, is a frequent but little-studied condition. Available prevalence data are based on selected patient populations or autopsy cases with their inherent bias. Objective The objective of this work is to evaluate the age-related incidence and secular trends in gynecomastia in the general population. Design An observational, 20-year national registry study was conducted. Setting This population-based study used nationwide registry data. Participants Participants included all Danish males (age 0-80 years) with a first-time diagnosis of gynecomastia. Main Outcome Measures All Danish males (age 0-80 years) were followed up for incident diagnosis of gynecomastia in the Danish National Patient Registry from 1998 to 2017 using the International Codes of Diseases, 10th revision, and the Danish Health Care Classification System. Age-specific incidence rates were estimated. The hypothesis tested in this study was formulated prior to data collection. Results Overall, a total 17 601 males (age 0-80 years) were registered with an incident diagnosis of gynecomastia within the 20-year study period, corresponding to 880 new cases per year and an average 20-year incidence of 3.4 per 10 000 men (age 0-80 years). The average annual incidence was 6.5/10 000 in postpubertal males age 16 to 20 years and 4.6/10 000 in males age 61 to 80 years, with a respective 5- and 11-fold overall increase in these 2 age groups over the 20-year period. Conclusions The incidence of gynecomastia has dramatically increased over the last 20 years, implying that the endogenous or exogenous sex-steroid environment has changed, which is associated with other adverse health consequences in men such as an increased risk of prostate cancer, metabolic syndrome, type 2 diabetes, or cardiovascular disorders.

scholarly journals Body Mass Index and Total Symptom Burden in Myeloproliferative Neoplasms Discovery of a U-shaped Association

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2202 ◽  
Author(s):  
Sarah Friis Christensen ◽  
Robyn Marie Scherber ◽  
Nana Brochmann ◽  
Martin Goros ◽  
Jonathan Gelfond ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Symptom Burden ◽  
Normal Weight ◽  
Analysis Of Covariance ◽  
Cross Sectional ◽  
Increased Risk

Elevated body mass index (BMI) is a global health problem, leading to enhanced mortality and the increased risk of several cancers including essential thrombocythemia (ET), a subtype of the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN). Furthermore, evidence states that BMI is associated with the severity of symptom burden among cancer patients. MPN patients often suffer from severe symptom burden. The purpose of this study was to examine whether deviations from a normal BMI in an MPN population are associated with higher symptom burden and reduced quality of life (QoL). A combined analysis of two large cross-sectional surveys, the Danish Population-based Study, MPNhealthSurvey (n = 2044), and the international Fatigue Study (n = 1070), was performed. Symptoms and QoL were assessed using the validated Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). Analysis of covariance was used to estimate the effects of different BMI categories on symptom scores while adjusting for age, sex, and MPN subtype. A U-shaped association between BMI and Total Symptom Burden was observed in both datasets with significantly higher mean scores for underweight and obese patients relative to normal weight (mean difference: underweight 5.51 (25.8%), p = 0.006; obese 5.70 (26.6%) p < 0.001). This is an important finding, as BMI is a potentially modifiable factor in the care of MPN patients.

scholarly journals Association between shiftwork and the risk of colorectal cancer in females: a population-based case–control study

2018 ◽  
Vol 75 (5) ◽  
pp. 344-350 ◽  
Author(s):  
Wa Mwenga Walasa ◽  
Renee N Carey ◽  
Si Si ◽  
Lin Fritschi ◽  
Jane S Heyworth ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Case Control Study ◽  
Early Morning ◽  
Population Based ◽  
Case Control ◽  
Colorectal Cancer Risk ◽  
Adverse Health Outcomes ◽  
Increased Risk ◽  
Control Study

ObjectiveResearch indicates that shiftwork may be associated with increased risks of adverse health outcomes, including some cancers. However, the evidence of an association between shiftwork and colorectal cancer risk is limited and inconclusive. Further, while several possible pathways through which shiftwork might result in cancer have been proposed, few studies have taken these factors into account. We investigated the association between two types of shiftwork (graveyard shiftwork and early-morning shiftwork) and six mechanistic shiftwork variables (including light at night and phase shift) and the risk of colorectal cancer among females in an Australian population-based case–control study. Graveyard shiftwork was the primary exposure of interest.MethodsParticipants (350 cases and 410 controls) completed a lifetime occupational history, and exposure to each of the eight shiftwork variables was assigned to participants through a job exposure matrix. We used logistic regression to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for the association between different shiftwork variables and the risk of colorectal cancer, adjusting for potential demographic, lifestyle and medical confounders.ResultsWorking in an occupation involving long-term exposure (>7.5 years) to graveyard shiftwork was not associated with colorectal cancer risk (adjusted OR 0.95, 95% CI 0.57 to 1.58). Similarly, no increased risks of colorectal cancer were seen for any of the other seven shiftwork variables examined.ConclusionsNo evidence of an increased risk of colorectal cancer among females who had worked in occupations involving shiftwork was observed in this study.

Prevalence of multiple sclerosis in Denmark 1950—2005

2010 ◽  
Vol 16 (5) ◽  
pp. 520-525 ◽  
Author(s):  
Joan Bentzen ◽  
Esben Meulengracht Flachs ◽  
Egon Stenager ◽  
Henrik Brønnum-Hansen ◽  
Nils Koch-Henriksen
Keyword(s):  
Multiple Sclerosis ◽  
Confidence Interval ◽  
Environmental Changes ◽  
Population Based ◽  
National Registry ◽  
Age At First Birth ◽  
Genetic Changes ◽  
Increased Risk ◽  
Using Data ◽  
Multiple Sclerosis Patients

Multiple sclerosis is an inflammatory disease of the central nervous system of unknown aetiology. Its prevalence varies by ethnicity and place: persons of northern European descent are at increased risk while persons living at lower latitudes appear to be protected against the disease. The Danish Multiple Sclerosis Registry is a national registry established in 1956 after a population-based survey which receives information from numerous sources. It is considered to be more than 90% complete, with a validity of 94%. Using data from the Registry, we calculated prevalences per 100,000 inhabitants. The standardized prevalence of multiple sclerosis increased from 58.8 (95% confidence interval: 54.9—62.7) in 1950 to 154.5 per 100,000 (95% confidence interval: 148.8—160.2) in 2005, and the female to male ratio increased from 1.31 in 1950 to 2.02 in 2005. The increase in prevalence is due to both increased survival of multiple sclerosis patients and an increased incidence rate. The rise in prevalence in the past 50 years is probably due more to environmental factors than to genetic changes in the Danish population. Among women, environmental changes could include older age at first birth, use of oral contraceptives, or changes in sun behaviour and/or vitamin D status.

TET2 and ASXL1 Mutations in Leukemic Transformation of Chronic Myeloproliferative Neoplasms.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2894-2894 ◽  
Author(s):  
Omar Abdel-Wahab ◽  
Taghi Manshouri ◽  
Jay Patel ◽  
Kelly Harris ◽  
Jin Juan Yao ◽  
...  
Keyword(s):  
De Novo ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Leukemic Transformation ◽  
Exact Test ◽  
Chronic Myeloproliferative Neoplasms ◽  
Secondary Acute Myeloid Leukemia ◽  
Paired Samples ◽  
Mutational Status ◽  
De Novo Aml

Abstract Abstract 2894 Poster Board II-870 Recent studies have identified TET2 and ASXL1 mutations in myeloid malignancies, suggesting that acquisition of these mutant alleles might precede the acquisition of JAK2 in some myeloproliferative neoplasm (MPN) patients. Moreover, the observation that JAK2 mutations are observed in minority of patients with leukemic transformation of JAK2-mutant MPNs suggests the possibility that JAK2 mutations are dispensable for leukemic transformation. However the role of TET2 and ASXL1 mutations in leukemic transformation has not been evaluated. We therefore investigated the mutational status of JAK2, TET2, and ASXL1 in 63 patients with leukemic transformation from a pre-existing MPN, including 49 unpaired secondary acute myeloid leukemia (sAML) samples and 14 patients for whom paired MPN and sAML samples were available. Mutations of TET2 and ASXL1 were found at a higher frequency in sAML samples transformed from MPNs than reported for sporadic MPNs (9/46 (19.6%) and 7/46 (15.2%), respectively). This was also higher than the mutational frequency of TET2 and ASXL1 in de novo AML (6.4% (3/47) and 4.3% (2/47), respectively) but similar to that of AML transformed from MDS (12.8% (5/39) and 15.4% (6/39)). All possible genetic combinations of JAK2, TET2, and ASXL1 status were observed in sAML patients. Analysis of paired samples reveal that TET2 mutations are far more likely to occur at leukemic transformation of MPN than at MPN diagnosis (p=0.013, Fisher's exact test) whereas ASXL1 mutations were equally likely to occur at MPN or sAML. Although mutations in JAK2 and in TET2 may not be retained at leukemic transformation from MPN, mutations in ASXL1 at MPN diagnosis were consistently retained at leukemic transformation. In addition, individual cases were observed where TET2 and/or ASXL1 mutations were found before acquisition of JAK2 mutations or clinical evidence of MPN, as well as cases where TET2 and ASXL1 mutations were acquired during leukemic transformation of a JAK2V617F-positive clone. These data suggest the mutational order of events in MPN and sAML pathogenesis might vary in different patients, and that TET2 and ASXL1 mutations might contribute in different patients to the development of MPN and/or to leukemic transformation. In addition, the identification of transformed AML cases with no evidence of pre-existing JAK2, TET2, and ASXL1 mutations indicates the existence of other, not yet identified, mutations necessary for leukemic transformation of MPNs. Disclosures: Levine: Novartis: Research Funding; TargeGen: Consultancy. Verstovsek:Incyte: ; Exelixis: ; Cephalon: ; SBIO: ; AstraZeneca: .

Family History Of Hematologic Malignancies and Disorders In a Population Based Study Of Myelodysplastic Syndromes (MDS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1541-1541
Author(s):  
Angela R. Smith ◽  
Erica D. Warlick ◽  
Rachel K. Fonstad ◽  
Michelle A. Roesler ◽  
Jenny N. Poynter ◽  
...  
Keyword(s):  
Family History ◽  
Conflicts Of Interest ◽  
Positive Family History ◽  
Hematologic Malignancies ◽  
Population Based ◽  
Newly Diagnosed ◽  
Population Based Study ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
History Of

Abstract Background MDS is a clonal hematopoietic stem cell disorder characterized by dysplastic changes in the bone marrow, ineffective hematopoiesis and an increased risk for developing acute myeloid leukemia (AML). The majority of MDS cases are sporadic, but rare familial cases have been described and are often ascertained through clinic-based referrals. To our knowledge, no population based study of MDS has examined the frequency of family history of hematologic malignancies and disorders in patients, nor associations with disease characteristics and outcomes. Methods Newly diagnosed MDS cases are being identified by rapid case ascertainment by the Minnesota Cancer Surveillance System (MCSS), a population-based cancer registry in Minnesota. Eligibility criteria include all newly diagnosed cases of MDS during the period April 1, 2010-October 31, 2014, between 20-85 years, Minnesota resident, and ability to understand English or Spanish. Proxy interviews are not being conducted. Medical records and biologic samples are obtained and questionnaires are filled out by participants. Centralized pathology and cytogenetics review confirm diagnosis and classify by subtype and risk score including the Revised International Prognostic Scoring System (IPSS-R). Since 2010, information on family history has been obtained through questionnaire responses and/or medical record review on 353 MDS patients. Cases were considered to have a positive family history if they reported a first degree relative with MDS, leukemia, lymphoma or other hematologic condition (multiple myeloma [n=4], Waldenstrom’s macroglobulinemia [n=1] and idiopathic thrombocytopenic purpura [n=1]). Treatment related MDS cases were excluded leaving 330 MDS patients for analysis. Unconditional logistic regression was used to calculate crude odds ratios (ORs) and 95% confidence intervals (CI) overall and by sex. Results A total of 61/330 (18.5%) cases reported a family history of a hematologic condition. The mean age at diagnosis was 71.3 years in those with a family history compared to 72.2 years in those without a family history (p=0.53). There was no difference in the sex distribution between the two groups. Though not statistically significant, the odds of having abnormal cytogenetics or an IPSS-R of High/Very High was lower for those having a positive family history (OR 0.57 [CI 0.25-1.33, p=0.19 and 0.67 [CI 0.24-1.84, p=0.29], respectively). The odds of survival at one year after diagnosis was significantly higher in those with a family history (OR 2.79 [CI 1.04-7.51, p=0.04]) compared to those without (Table). Further stratification by sex revealed that this association was strongest for males (OR=4.23, [CI 0.94-19.0, p=0.06] compared to females (OR=1.84 [CI=0.47-7.19, p=0.38]). Discussion In this population based study of adults with MDS, the prevalence of MDS cases having a positive family history was higher than previous reports. Additionally, cases reporting a family history of hematologic malignancies and disorders appear to experience lower risk disease and have significantly improved overall survival, especially males. It is possible that patients with a family history of hematologic conditions are diagnosed earlier in the course of their disease secondary to increased awareness about blood disorders and/or more active screening within the family. Our analysis is limited by relatively small numbers, but enrollment is ongoing so subsequent analyses with larger numbers of subjects may be more revealing. Additionally, a prospective study to examine these families further, including detailed medical histories and collection of biospecimens (saliva, blood, skin) for genetic analyses is underway in order to identify potential mechanisms and mutations involved in the development of MDS and progression to AML. Disclosures: No relevant conflicts of interest to declare.

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