scholarly journals Familial Risk and Heritability of Hematologic Malignancies in the Nordic Twin Study of Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3023
Author(s):  
Signe B. Clemmensen ◽  
Jennifer R. Harris ◽  
Jonas Mengel-From ◽  
Wagner H. Bonat ◽  
Henrik Frederiksen ◽  
...  

We aimed to explore the genetic and environmental contributions to variation in the risk of hematologic malignancies and characterize familial dependence within and across hematologic malignancies. The study base included 316,397 individual twins from the Nordic Twin Study of Cancer with a median of 41 years of follow-up: 88,618 (28%) of the twins were monozygotic, and 3459 hematologic malignancies were reported. We estimated the cumulative incidence by age, familial risk, and genetic and environmental variance components of hematologic malignancies accounting for competing risk of death. The lifetime risk of any hematologic malignancy was 2.5% (95% CI 2.4–2.6%), as in the background population. This risk was elevated to 4.5% (95% CI 3.1–6.5%) conditional on hematologic malignancy in a dizygotic co-twin and was even greater at 7.6% (95% CI 4.8–11.8%) if a monozygotic co-twin had a hematologic malignancy. Heritability of the liability to develop any hematologic malignancy was 24% (95% CI 14–33%). This estimate decreased across age, from approximately 55% at age 40 to about 20–25% after age 55, when it seems to stabilize. In this largest ever studied twin cohort with the longest follow-up, we found evidence for familial risk of hematologic malignancies. The discovery of decreasing familial predisposition with increasing age underscores the importance of cancer surveillance in families with hematological malignancies.

Blood ◽  
2020 ◽  
Vol 136 (25) ◽  
pp. 2881-2892
Author(s):  
Abi Vijenthira ◽  
Inna Y. Gong ◽  
Thomas A. Fox ◽  
Stephen Booth ◽  
Gordon Cook ◽  
...  

Abstract Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Jacobsen ◽  
D Modin ◽  
L Koeber ◽  
E L Fosboel ◽  
A Axelsson

Abstract Background Patients with hypertrophic cardiomyopathy (HCM) are generally considered to have an increased morbidity and mortality due to symptomatic heart failure, atrial fibrillation, stroke and sudden cardiac death. Data reporting the mortality compared with background populations are however conflicting and primarily based on small cohorts from tertiary centers. Purpose We aimed to investigate whether a nationwide cohort of patients with HCM had an increased risk of death compared with a matched cohort derived from the general Danish population. Methods Using nationwide registries, we identified all patients with a first-time HCM diagnosis in Denmark between 2007 and 2016. Patients were matched 1:5 on age, sex and HCM diagnosis date to controls using risk set sampling. The study population was followed until death, emigration, or end of study period Jan. 1, 2017–whichever came first. Mortality was compared using Kaplan Meier plots and multivariable adjusted Cox proportional hazard analysis. Results We identified 3010 patients diagnosed with HCM (53.8% male) per registry codes. Men were on average 8.5 years younger at diagnosis than women (62.6 years [p25-p75: 49.8–73.9] vs. 71.1 years [p25-p75: 59.7–80.6]). Patients with HCM had more comorbidities than matched controls. The median time of follow-up was 4.4 years (p25-p75: 2.3, 6.7). For HCM patients and matched controls, 1-year, 5-year and 10-year probabilities of death were 10% (95% CI 9–12%), 28% (95% CI 26–30%) and 47% (95% CI 42–51%) and 2% (95% CI 1–3%), 13% (95% CI 12–14%) and 24% (95% CI 23–25%) respectively (Figure 1). After adjusting for comorbidities and medications a diagnosis of HCM was associated to a 107% increased risk of death (hazard ratio 2.07 [95% confidence interval 1.60, 2.68], p<0.0001). Figure 1 Conclusion In a Danish nationwide cohort, HCM was associated with a significantly higher risk of death compared with the background population. This study emphasizes the importance of continued, life-long follow-up of patients with HCM with the aim to anticipate and treat preventable adverse events. Furthermore, the findings stress the need to develop effective disease-modifying treatment strategies.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5000-5000
Author(s):  
Meera Sridharan ◽  
Aref Al-Kali ◽  
Aneel A. Ashrani ◽  
Kebede Begna ◽  
Michelle Elliott ◽  
...  

Abstract Background Tunneled central venous catheters have traditionally been used for administration of chemotherapy (chemo) for acute leukemia treatment. Peripherally inserted central catheters (PICC) are increasingly being used, but there is an increased risk of PICC-associated thrombosis (PAT). There is limited information on management of PAT in this subgroup of patients (pt). Methods In this retrospective cohort study we investigated the primary management of PICC related upper extremity venous thrombosis (TB) in pt with hematologic malignancy undergoing chemo at Mayo Clinic Rochester.  Eligible pt were 18 years and older, had documentation of PICC placement at our institution, initiation of chemo within a week of PICC placement, and the TB was objectively documented by compression venous ultrasound (CVU).   Superficial venous TB (SVT) was defined as TB of subcutaneous veins (basilic and cephalic) and deep venous TB (DVT) defined as TB of brachial, axillary, subclavian, or innominate superior vena cava and internal jugular veins. We retrospectively stratified initial management (IM) into 1) PICC removal alone (PR), 2) PR and therapeutic anticoagulation (AC), 3) AC alone, and 4) conservative management (CM) consisting of symptomatic care and observation.  We also investigated factors influencing IM of PAT.  Long term outcomes including incidence of pulmonary embolism (PE), post phlebitic syndrome and recurrence of TB were noted. Results Between 2006 and 2012, 190 pt with AML (n=160), MDS or MDS/MF (n=10), or ALL (n=20) met our study criteria.  Overall, 40/190 (21.6%) developed PAT: AML n=38, ALL n=1, MDS/MF n=1. SVT occurred in 16/40 (40%) pt and DVT occurred in 24/40 (60%) pt. IM is shown in Table 1. One pt with SVT received AC for 6 weeks as well as PR.  In this pt, IM included AC because of proximity of TB to deep veins. 7 pt had a follow up (f/u) CVU within 3 months demonstrating: TB progression (prog, n=1, IM with PR alone but with prog AC was started); TB stability (stab, n=2, both IM with PR alone) and TB resolution/improvement (R/I, n= 4, 2 IM with PR and 2 IM with CM)  In the 5 pt with CM, 2 pt had f/u CVU demonstrating improvement, one pt had charted clinical improvement , and 2 pt had no charted clinical f/u. Of DVT pt on AC (n=14), 5 pt completed at least 2 months of AC.  Reasons for early cessation (n=9) of AC included thrombocytopenia (tcp, n=4), hematoma (n=1), hematuria (n=1), subarachnoid hemorrhage (n=1), and unknown (n=1).   One pt died 2 days after presence of DVT was noted. Two pt initially treated with PR alone developed a second TB with placement of a new PICC on contralateral arm and AC was subsequently initiated (duration: 3 months (n=1), and 8 days (n=1)). 14 pt with DVT had f/u CVU within 3 months which demonstrated prog (n=2), stab (n= 8), or R/I ( n=4) of TB (Table 2). The 2 pt with TB prog subsequently received longer term AC guided by platelet count.   In 5 pt with PICC not initially removed, 3 pt had PR after completion of chemo. (1-4 days), one pt had PR at discharge (27 days from TB), and one pt had PICC in place on discharge. One pt with DVT experienced a PE within one year f/u.  This pt had initially completed 3 days of AC which was stopped because of tcp. Conclusion In this cohort of patients with PAT, the most common IM consisted of PR, which appeared to result in a low recurrence rate among pt with SVT.  In pt with DVT, the role of AC remains to be defined given the abbreviated course of AC in most pt.  Though, the lack of CVU followup in all pt limits conclusions, there appeared to be a low rate of symptomatic prog.  Initiation of AC was largely guided by platelet count and degree of occlusive symptoms. Thrombocytopenia was also the most commonly cited reason for discontinuing AC.  Close clinical follow up aided by the use of CVU was integral to ensure that PAT did not lead to further adverse events. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1933-1933
Author(s):  
Adam Suleman ◽  
Abi Vijenthira ◽  
Alejandro Berlin ◽  
Anca Prica ◽  
Danielle Rodin

Abstract Background: The use of virtual care, defined as providing healthcare in ways other than in-person visits, dramatically increased during the COVID-19 pandemic to minimize infection risk and maintain care provision. However, the majority of studies evaluating the use of virtual care in oncology have focused on patients with solid tumor malignancies. Patients with hematologic malignancies represent a unique population related to their underlying malignancy and treatment, but the extent to which virtual care has been successfully integrated into clinical practice is unknown. As the demand for incorporating virtual care into routine clinical practice grows, understanding how to safely and effectively use virtual care in this specific patient population is essential. Methods: A scoping review was conducted to describe the use of virtual care in the management of patients with hematologic malignancies and to examine physician- and patient-reported outcomes based on its use. A comprehensive search strategy was used to identify articles on the use of virtual modalities (digital applications, phone visits, or video visits) to deliver routine clinical care to patients with hematologic malignancies published in English between January 2000 and April 2021 in the following databases: PubMed, Medline, EMBASE, CINAHL and Scopus. No restrictions were applied to the phase of care (surveillance, active treatment, and or survivorship). A combination of search terms to encompass hematologic malignancies and virtual care was used. Screening and data abstraction were performed by two independent reviewers (AS, AV) and conflicts were adjudicated by two additional reviewers (DR, AP). Data were extracted to assess the study design, population, setting, patient characteristics, virtual care methodology and study results. Results: A total of 350 abstracts were screened and 60 studies underwent full-text review. Of these, 15 studies met inclusion criteria (13 retrospective studies, 1 prospective pilot study, and 1 randomized controlled trial). The majority of papers were published from 2020 onward (Figure 1). Three studies found that app-based tools were effective in monitoring patient symptoms and triggering alerts which resulting in sooner follow-up if indicated. One app-based tool was also used in a resource limited country during the COVID-19 pandemic to allow for communication between hematologists and their patients. Four studies described the use of phone-based interventions for new consults and follow-up visits. Phone visits for used even in high-risk patients (for example, in 29 out of 50 patients with chronic graft-versus-host disease after allogeneic stem cell transplant). Five studies found that videoconferencing, with both physicians and oncology nurses, was highly rated by patients. Emerging themes included high levels of patient satisfaction across all domains of virtual care. Provider satisfaction scores were rated lower than patient scores, with concerns about technical issues leading to challenges with virtual care. Four studies found that virtual care allowed providers to promptly respond to patient concerns, specifically when patients were experiencing side-effects or had questions about their treatment. One study also suggested a decreased risk of death when telemedicine was used to monitor symptoms in patients with diffuse large B-cell lymphoma. There were no data addressing the impact of virtual care on costs or resource utilization. Conclusion: The use of virtual care in patients with hematologic malignancies appears to be feasible, even in high-risk populations. Patients were highly satisfied with virtual care, although providers had some challenges related to the specific technologies. More research is needed to evaluate the optimal method of integrating virtual care, informed by a wider range of patient-related outcomes, as well as the downstream consequences of this integration for patient, providers, and health systems. Figure 1 Figure 1. Disclosures Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3830-3830
Author(s):  
Gregory A. Abel ◽  
Christopher R. Friese ◽  
Bridget A. Neville ◽  
Lisa C. Richardson ◽  
Katherine M. Wilson ◽  
...  

Abstract Abstract 3830 Background: Although the primary care physician (PCP) is often the first point of contact for patients with suspected hematologic malignancy, little is known about hematologic referrals from primary care, including their frequency, the factors that affect choice of specialist, and the quality of information exchanged. Methods: In April 2010, we administered a 34-item questionnaire to a random sample of 190 physicians in the state of Massachusetts identified as PCPs (family practice, general practice, or internal medicine) in the American Medical Association's physician file. PCPs were given the opportunity to complete the survey via post or Internet. An additional mailing was sent to non-respondents, followed by at least two attempts at telephone contact. Physicians were asked for the approximate number of patients seen in the past year with suspected hematologic malignancy, the frequency of formal specialty referral, and informal “curbside” referral. PCPs were also queried about the factors that influence their choice of specialist, and about the information exchange with the specialist; these measures were then analyzed by self-reported PCP characteristics using chi-square statistics. Results: As of August, 2010, 118 physicians had responded (response rate = 62.1%). 67.8% identified themselves as internists, and 61.9% were male. The median reported patient panel size during the prior 12 months was 1800; median percentage of patients ≥ 65 years was 30.0%; median percentage of patients in managed care was 55.0%; and median year of graduation from residency, 1996. PCPs were evenly distributed with respect to academic affiliation (from no affiliation to full-time faculty). The median number (IQR) of patients in the prior 12 months who were suspected of having hematologic malignancy was 5 (3, 10). Among suspected hematologic malignancies, the median number formally referred to a specialist (hematologist or surgeon) was 5 (3, 10), and the median number who received informal “curbside” consult was 0 (0, 0.5). Respondents rated the importance of several factors in their choice of specialist (1 = not important at all to 5 = extremely important). Those factors rated ≥ 3 included reputation of specialist/facility (94.9%), patient's preference for site of care (92.4%), distance of site from patient's home (89.8%), specialist's affiliation with a cancer center (88.1%), practice's affiliation with specialist (82.2%), personal relationship with specialist (79.7%), patient's ability to pay (67.0%), and availability of clinical trials at the referral site (63.6%). The following table summarizes responses to questions about flow of referral information and follow-up: Conclusions: Consultation for suspected hematologic malignancy from PCPs is relatively infrequent, tends to manifest through formal referral as opposed to informal discussion, and is most often affected by specialist reputation and patient preference for site of care. Only about half of our respondents reported providing the specialist with a referral letter or email, which may result in poor quality of referral information. Alternately, a high number reported giving a copy of abnormal test results to their patients to bring to the specialist, which may ameliorate this issue and reflect an ongoing evolution in the patient/provider partnership. Moreover, fairly often, patients have not been to see the specialist upon follow-up with their PCP. This finding seems to reflect patient cancellations rather than a failure in physician systems, suggesting that increases in patient education and personalized follow-up may be the best approach to ensure completion of timely hematologic referrals. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
pp. 140349482095332 ◽  
Author(s):  
Merete Osler ◽  
Martin Dalgaard Villumsen ◽  
Martin Balslev Jørgensen ◽  
Jacob V.B. Hjelmborg ◽  
Kaare Christensen ◽  
...  

Aim: Our aim was to explore whether familial factors influence the risk of ischemic heart disease, stroke, and their co-occurrence. Methods: In total, 23,498 monozygotic and 39,540 same-sex dizygotic twins from the Danish Twin Registry were followed from 1977 to 2011 in the Danish National Patient Registry for ischemic heart disease and stroke. Time-to-event analyses accounting for censoring and competing risk of death were used to estimate familial risk (casewise concordance relative to the cumulative incidence) and heritability of ischemic heart disease, stroke, and the co-occurrence by age. Results: During follow-up, we observed 5561 and 4186 twin individuals with ischemic heart disease and stroke respectively, with 936 twin pairs concordant for ischemic heart disease and stroke. Familial risks were significant for both, with higher cumulative risks in monozygotic than in dizygotic twins. Estimates for heritability were significant for ischemic heart disease as well as for stroke diagnosed after the age of 80. The casewise concordance of ischemic heart disease in twins whose co-twin was diagnosed with stroke did not differ for monozygotic and dizygotic twins; however, from age 55 it was 10% higher than the cumulative risk in the overall twin cohort and was 25% higher at age 90. A similar pattern was seen for stroke following the co-twin’s ischemic heart disease. Conclusions: As in previous studies, we found a higher heritability of ischemic heart disease than of stroke. There was a significant familial risk but no heritability for the co-occurrence of ischemic heart disease and stroke. The co-occurrence is therefore likely due to other shared familial than genetic factors, highlighting that preventive initiatives should target families rather than individuals.


Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 682-682
Author(s):  
Luciano J. Costa ◽  
Kelly N. Godby ◽  
Saurabh Chhabra ◽  
Robert Frank Cornell ◽  
Parameswaran Hari ◽  
...  

Background: The management of patients with multiple myeloma (MM) has evolved significantly over the last two decades with increased utilization of autologous hematopoietic cell transplantation (AHCT) and introduction of proteasome inhibitors (PIs) and immunomodulatory agents (IMIDs) and concomitant improvement in survival, particularly in younger patients. Both AHCT and the IMID lenalidomide have been associated with increased risk of second malignant neoplasms (SMN) in clinical trials, with the risk reaching 6.9% at 5 years in a recent meta-analysis. We intended to assess whether an increase in incidence of SMN was evident at the population level and the impact of the changing SMN risk on survival of MM patients. Methods: We utilized the Surveillance, Epidemiology and End Results 13 (SEER 13) registries to analyze three cohorts of patients: those diagnosed during 1995-1999 (pre-thalidomide, limited use of AHCT, 15 years of follow up), 2000-2004 (post-thalidomide, pre lenalidomide and bortezomib, increased utilization of AHCT, 10 years of follow up) and 2005-2009 (post-lenalidomide and bortezomib, higher utilization of AHCT, 5 years of follow up). Follow up is current to the end of 2014. We included patients younger than 65 years at the time of diagnosis of MM as first malignant neoplasm to focus the analysis in patients more likely to receive AHCT and presumably prolonged lenalidomide exposure. For each cohort, we calculated the incidence of SMN considering death from any cause as a competing risk. Since comparison by era is subject to confounding by attained age, we analyzed and compared standardized incidence ratios (SIRs) for SMN and causes of death (COD) in intervals of 5 years: years 1-5 and years 6-10 from diagnosis. Results: There were 2,720 patients in the 1995-1999, 3,246 in the 2000-2004 and 3,867 in the 2005-2009 cohort. Median age of diagnosis was 56 years and 56.6% of the patients were males with no differences across cohorts. Non-Hispanic Whites were 55.9%, non-Hispanic Blacks 23.2%, Hispanics 12.6% and individuals of other race/ethnicities 8.2%. Median follow up of survivors was 198 months (range 1-239), 141 months (range 1-179) and 81 months (range 0-119) in the 1995-1999, 2000-2004 and 2005-2009 cohorts respectively. Cumulative incidences of SMN at 90 months were 4.7% (95% C.I. 4.0-5.6%), 6.0% (95% C.I. 5.2%-6.8%) and 6.3% (95% C.I. 5.5%-7.1%), respectively in the 3 consecutive cohorts, P=0.0008. The statistically significant, yet small increase in SMN is accompanied with decline in all-cause mortality in the same period from 69.9% for the 1995-1999 cohort to 60.4% for the 2000-2004 cohort to 52.8% for the 2005-2009 cohort, P&lt;0.0001. During years 1-5 after MM diagnosis, the risk of another cancer of any type evolved from lower than expected in an age, gender and race-matched population for patients diagnosed in 1995-1999 (SIR=0.77, 95% C.I. 0.59-0.99) to similar to expected for patients diagnosed in 2005-2009 (SIR=1.15, 95% C.I. 0.97-1.36), driven particularly by increase in hematologic malignancies from SIR=1.28 (95% C.I. 0.47-2.78) to SIR=2.17 (95% C.I. 1.27-3.48),(Figure). For years 6-10, the overall risk of subsequent malignancy in MM survivors is similar to the matched population for both the 1995-1999 and the 2000-2004 cohorts (most recent cohort with 10-year follow up). However, the risk of subsequent hematologic malignancy is increased in both periods with the most substantial change being in the risk of lymphomas evolving from SIR=0.59 (95% C.I. 0.01-3.29) for the 1995-1999 cohort to SIR=3.31 (95% C.I. 1.51-6.27) for the 2000-2004 cohort. As expected, overall mortality in years 1-5 declined sharply across the three cohorts (Table), driven by decline in both MM-associated (from 159.4 to 91.7/1,000 patient-year) and cardiovascular mortality (from 12.6 to 9.1/1,000 patient-year). Importantly, there was no discernible increase in risk of death from SMN (from 4.5 to 3.9/1,000 patient-year). Conclusions: This population study confirms that the evolution of MM therapy in the US in the last 20 years is associated with a small, statistically significant increase in the risk of SMN in patients &lt;65 years. Such increase is driven mostly by the increased incidence of hematologic malignancies. The study also demonstrates that the mortality from SMN is modest, has not significantly increased over time and is obscured by the robust reduction in mortality from MM. Disclosures No relevant conflicts of interest to declare.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S317-S317
Author(s):  
Shelby Daniel-Wayman ◽  
Gary Fahle ◽  
Tara Palmore ◽  
Kim Green ◽  
D Rebecca Prevots

Abstract Background Norovirus, astrovirus, and sapovirus are known to cause acute gastroenteritis and are associated with chronic viral excretion in stool among immunocompromised patients. Because molecular tools for their detection only recently became widely available, the prevalence and chronic excretion of these viruses has not been well defined. We describe features of these viral infections among patients receiving care at the Clinical Center of the National Institutes of Health. Methods We identified patients with a positive BioFire FilmArray® gastrointestinal panel result for norovirus, astrovirus, or sapovirus from September 15, 2015 through November 30, 2016. We reviewed patient medical records to abstract clinical and microbiologic information. Chronic excretion was defined as more than one positive test for a given virus with more than 30 days between tests. Results Of 932 samples tested, 102 (11%) samples from 48 patients tested positive for norovirus, 15 (2%) samples from 11 patients tested positive for sapovirus, and 16 (2%) samples from 7 patients tested positive for astrovirus. One of these patients had a sample that tested positive for both sapovirus and norovirus, and one tested positive for astrovirus and sapovirus at separate points during the study period. Of the 48 patients with norovirus, 16 (33%) had evidence of chronic excretion, with a median duration of 189 days (range 72–372). Of these 16, 14 were known or suspected to be immunodeficient, and 4 had hematologic malignancies. Of 7 patients with astrovirus, 1 (14%) had evidence of chronic excretion (132 days). This patient had a hematologic malignancy and was taking immunosuppressive medication. No patients with sapovirus had evidence of chronic excretion. Overall, 20 (31%) patients additionally tested positive for another gastrointestinal pathogen, most commonly enteropathogenic E. coli and C. difficile. Conclusion Norovirus remains common in this immunocompromised patient population, and both sapovirus and astrovirus are present. Additional follow-up in this and other cohorts with new molecular tools will enable more complete description of the prevalence, excretion duration, and clinical features of infection with these enteric viruses. This research was supported by the Intramural Research Program of the NIH, NIAID, and the NIH CC. Disclosures All authors: No reported disclosures.


2006 ◽  
Vol 22 (3) ◽  
pp. 111-117 ◽  
Author(s):  
A. De Silvestri ◽  
C. Belloni ◽  
M. De Amici ◽  
P. Mazzola ◽  
M. Zorzetto ◽  
...  

Aim:We investigated on parental history and IgE serum level in 2588 consecutive newborns to individuate babies “at risk” of atopy at birth and we analysed the polymorphisms of class III region to evaluate the association with immunogenetic markers of HLA: C4A, C4B, LTA, RAGE and TNFA genes; we performed TNF and IgE receptor (FCERB1) physiologically related gene polymorphisms.Result:791 babies/2588 (30.6%) were considered “at risk” for atopy and followed-up: 400 had familial history of atopy (at least one parent or sibling), 256 had IgE > 0.35 kUA/l at birth and during the follow-up and 135 were positive for both conditions.The allele C4B2 was significantly more frequent in the sample of babies at risk (22.1% vs 10%,p< 0.001). Furthermore, the mean value of IgE at birth in babies carrying the allele C4B2 was 2.26 KUA/l versus 0.74 KUA/l in those not carrying this allele (p= 0.01). No significant association emerged for RAGE at the centromeric end of class III region and for LTA, TNFA at the telomeric one. TNFRI, TNFRII and FCERB1 gene polymorphisms also seemed not implicated.Conclusion: Our study confirms that HLA class III region seems involved in familial predisposition to atopy, and C4B gene probably acts as a marker of a more restricted subregion.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 11-11
Author(s):  
Lorelei A. Mucci ◽  
Jacob Hjelmborg ◽  
Kathryn Penney ◽  
Axel Skytthe ◽  
Jennifer Harris ◽  
...  

11 Background: Twin studies estimate familial risk and heritability by leveraging the unique genetic relatedness of twins. We analyzed data from the Nordic Twin Study to investigate the genetic underpinnings of risk of genitourinary cancers. Methods: The cohort included 202,868 monozygotic (MZ) and same-sex dizygotic (DZ) twins from nationwide registries with follow-up via cancer registries. We examined cancers of the prostate, bladder, kidney and testes, and estimated familial risk, risk of a specific cancer in a twin, given that his co-twin was diagnosed with the same cancer, and heritability, the proportion of variation in cancer risk due to genetic differences. Statistical models used time-to-event analyses and accounted for censoring and competing risk of death. Results: During 32 years of follow-up, 5,041 cases of genitourinary cancer were diagnosed. The cumulative incidences in the cohort overall were 10.5% for prostate, 2.2% for bladder, 0.8% for kidney and 0.5% for testes. The strongest familial effects were found for testicular cancer. The familial risks of testicular cancer were 6% for DZ and 14% for MZ twins, i.e. a 12-fold and 28-fold higher risk for DZ and MZ twins, respectively, when their twin was also diagnosed with testicular cancer. Familial risk was also elevated for prostate, bladder, and kidney cancer and showed higher estimates among MZ than DZ twins. Statistically significant estimates of heritability were observed for prostate (57%) and kidney (38%) cancer, while testicular cancer showed evidence of both genetic (37%) and shared environmental (24%) effects. Conclusions: Familial risk estimates provide evidence of significant excess risks for individuals whose siblings develop genitourinary cancers. The higher concordance in MZ vs. DZ twins translated to strong heritability estimates for these malignancies. Results from this study have the potential to be directly translated to clinical practice and genetic counseling, and provide a context for the findings from genome wide association studies.


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