RESUMO
BACKGROUND: Since the early 2000s, overall and site-specific cancer survival have improved substantially in the Nordic countries. We evaluated whether the improvements have been similar across countries, major cancer types, and age groups. MATERIAL AND METHODS: Using population-based data from the five Nordic cancer registries recorded in the NORDCAN database, we included a cohort of 1,525,854 men and 1,378,470 women diagnosed with cancer (except non-melanoma skin cancer) during 2002-2021, and followed for death until 2021. We estimated 5-year relative survival (RS) in 5-year calendar periods, and percentage points (pp) differences in 5-year RS from 2002-2006 until 2017-2021. Separate analyses were performed for eight cancer sites (i.e. colorectum, pancreas, lung, breast, cervix uteri, kidney, prostate, and melanoma of skin). RESULTS: Five-year RS improved across nearly all cancer sites in all countries (except Iceland), with absolute differences across age groups ranging from 1 to 21 pp (all cancer sites), 2 to 20 pp (colorectum), -1 to 36 pp (pancreas), 2 to 28 pp (lung), 0 to 9 pp (breast), -11 to 26 pp (cervix uteri), 2 to 44 pp (kidney), -2 to 23 pp (prostate) and -3 to 30 pp (skin melanoma). The oldest patients (80-89 years) exhibited lower survival across all countries and sites, although with varying improvements over time. INTERPRETATION: Nordic cancer patients have generally experienced substantial improvements in cancer survival during the last two decades, including major cancer sites and age groups. Although survival has improved over time, older patients remain at a lower cancer survival compared to younger patients.
Assuntos
Melanoma , Neoplasias , Masculino , Humanos , Feminino , Melanoma/epidemiologia , Melanoma/terapia , Taxa de Sobrevida , Fatores de Risco , Seguimentos , Países Escandinavos e Nórdicos/epidemiologia , Neoplasias/epidemiologia , Neoplasias/terapia , Neoplasias/diagnóstico , Sistema de Registros , Análise de Sobrevida , IncidênciaRESUMO
BACKGROUND AND PURPOSE: This study is the first report regarding childhood cancer in the Faroe Islands and describes the incidence and survival of childhood cancer over the last 60 years in the Faroe Islands. MATERIAL AND METHODS: We included all Faroese children registered with a cancer diagnosis up to the age of 19 years in the Faroese Cancer Registry from 1960 to 2019 and in the Danish Childhood Cancer Registry from 1985 to 2019 in this study. We report the number of incident cancers classified according to the 12 main diagnostic groups in the International Classification of Childhood Cancer, third edition (ICCC-3), but due to small numbers some groups have been combined in the results shown. We report age-standardized incidence rates (world standard population) (ASIR). We also show all-cause survival by incidence stratified by 20-year periods. RESULTS: There were 114 childhood cancers in the Faroe Islands from 1960 to 2019, corresponding to an ASIR of 13.0 per 100,000 person-years. The most common cancer groups in Faroese children were brain and spinal tumors, followed by leukemias and lymphomas. All-cause survival improved for children diagnosed over time, with a 5-year survival of 43.5% for those diagnosed from 1960 to 1979 and 85.6% for children diagnosed from 2000 to 2019. CONCLUSION: Childhood cancer in the Faroes was slightly rarer than in most other high-income countries. Brain and spinal tumors were the most common cancer group in Faroese children. Survival for Faroese children with cancer has improved substantially in the study period.
Assuntos
Neoplasias do Sistema Nervoso Central , Neoplasias , Neoplasias da Coluna Vertebral , Criança , Humanos , Adulto Jovem , Adulto , Neoplasias/epidemiologia , Incidência , Dinamarca/epidemiologia , Sistema de RegistrosRESUMO
As sustained development in cancer treatment protocols have led to improved survival in most areas of the world, surveillance is needed to ensure that small populations follow suit. Our study reports age-standardized relative cancer survival in the Faroe Islands compared to the other Nordic countries. We present 1- and 5-year survival estimates and corresponding 95% confidence intervals for the Faroe Islands and compare them with estimates for the Nordic countries. The data for this article has been obtained through the NORDCAN collaboration (2019 data). Age-standardized relative survival was estimated using shared R codes on individual-level data within each country. Ten-year calendar inclusion periods were used in addition to the usual 5-year calendar periods to include cancer sites with few cases, which is especially beneficial to the smaller populations. The primary findings were that 1- and 5-year survival were consistently lower in the Faroes for the summary group all sites but non-melanoma skin cancer for both women and men. Further, 5-year survival was lower for women with ovarian cancer and men with lung cancer than in other Nordic countries. Previously, breast cancer survival was low in the Faroes but has improved to a comparable level over the last few years. Colorectal cancer survival was relatively high for both sexes. The reported estimates in this article call for further research to investigate the cancers with lower survival and should call for actions to improve the survival of Faroese cancer patients.
Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Países Escandinavos e Nórdicos , Dinamarca/epidemiologia , Incidência , Sistema de Registros , Fatores de RiscoRESUMO
BACKGROUND: Hope is an integral part of a dying person's needs and an important phenomenon that has not been satisfactorily explored. The tension between hope for a cure and the reality of being terminally ill is a paradox, which in the context of palliative cancer care, nurses and health care professionals must take into consideration. OBJECTIVE: The purpose of this study was to elucidate the phenomenon of hope and to investigate the lived experiences of hope among newly diagnosed patients with advanced cancer. METHOD: The study used a phenomenological-visual method where drawings and post-drawing interviews were used. The participants were six patients who recently had been offered specialised palliative care treatment. They were five women and one man with different cancer diagnoses and between 30 and 82 years of age (median 65 years). The data consisted of six drawings and individual post-drawing interviews with the participants. The study was reported using the COREQ checklist. RESULTS: The study revealed one main concern 'Being in hope' and hope appeared in four different dimensions; internal, external, relational and transcendental. Hopelessness was present at all times. CONCLUSION: Hope pictured in drawings was expressed through colour, shape, lines, symbols and metaphors, and hope incorporated internal, external, relational and transcendental aspects. Hope was constantly fighting against hopelessness and hope integrated with past, present and future. RELEVANCE TO CLINICAL PRACTICE: Drawings, as well as other visual representations, are suitable tools when trying to understand an ineffable phenomenon such as hope experienced by people newly diagnosed with cancer.
Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Masculino , Humanos , Feminino , Idoso , Neoplasias/terapia , Afeto , Lista de Checagem , Pessoal de SaúdeRESUMO
BACKGROUND: The durability of SARS-CoV-2 antibody response and the resulting immunity to COVID-19 is unclear. OBJECTIVES: To investigate long-term humoral immunity to SARS-CoV-2. METHODS: In this nationwide, longitudinal study, we determined antibody response in 411 patients aged 0-93 years from two waves of infections (March to December 2020) contributing 1063 blood samples. Each individual had blood drawn on 4-5 occasions 1-15 months after disease onset. We measured total anti-SARS-CoV-2 receptor-binding domain (RBD) antibody using a qualitative RBD sandwich ELISA, IgM, IgG and IgA levels using an quantitative in-house ELISA-based assay and neutralizing antibodies (NAbs) using an in-house ELISA-based pseudoneutralizing assay. IgG subclasses were analyzed in a subset of samples by ELISA-based assay. We used nonlinear models to study the durability of SARS-CoV-2 antibody responses and its influence over time. RESULTS: After 15 months, 94% still had detectable circulating antibodies, mainly the IgG isotype, and 92% had detectable NAbs. The distribution of IgG antibodies varied significantly over time, characterized by a biphasic pattern with an initial decline followed by a plateau after approximately 7 months. However, the NAbs remained relatively stable throughout the period. The strength of the antibody response was influenced by smoking and hospitalization, with lower IgG levels in smokers and higher levels in hospitalized individuals. Antibody stability over time was mainly associated with male sex and older age with higher initial levels but more marked decrease. CONCLUSIONS: The humoral immune response to SARS-CoV-2 infection varies depending on behavioral factors and disease severity, and antibody stability over 15 months was associated with sex and age.
Assuntos
COVID-19 , Humanos , Masculino , Estudos Longitudinais , SARS-CoV-2 , Anticorpos Antivirais , Anticorpos Neutralizantes , Imunoglobulina G , Dinamarca , ImunidadeRESUMO
Here we present results from FarGen Phase I exomes. This dataset is based on the FarGen cohort, which consists of 1,541 individuals from the isolated population of the Faroe Islands. The purpose of this cohort is to serve as a reference catalog of coding variants, and to conduct population genetic studies to better understand the genetic contribution to various diseases in the Faroese population. The first whole-exome data set comprise 465 individuals and a total of 148,267 genetic variants were discovered. Principle Component Analysis indicates that the population is isolated and weakly structured. The distribution of variants in various functional classes was compared with populations in the gnomAD dataset; the results indicated that the proportions were consistent across the cohorts, but probably due to a small sample size, the FarGen dataset contained relatively few rare variants. We identified 19 variants that are classified as pathogenic or likely pathogenic in ClinVar; several of these variants are associated with monogenetic diseases with increased prevalence in the Faroe Islands. The results support previous studies, which indicate that the Faroe Islands is an isolated and weakly structured population. Future studies may elucidate the significance of the 19 pathogenic variants that were identified. The FarGen Phase I dataset is an important step for genetic research in the Faroese population, and the next phase of FarGen will increase the sample size and broaden the scope.
Assuntos
Exoma , Projetos de Pesquisa , Humanos , Dinamarca/epidemiologia , PrevalênciaRESUMO
Symptoms of long coronavirus disease (COVID) were found in 38% of 170 patients followed for a median of 22.6 months. The most prevalent symptoms were fatigue, affected taste and smell, and difficulties remembering and concentrating. Predictors for long COVID were older age and number of symptoms in the acute phase. Long COVID may take many months, maybe years, to resolve.
RESUMO
OBJECTIVES: Persistence of COVID-19 symptoms in nonhospitalized individuals beyond a few months has not been well characterized. In this longitudinal study from the Faroe Islands, we present prevalence of long COVID in mainly nonhospitalized patients who were followed up for up to 8 months. METHODS: All Faroese individuals with confirmed COVID-19 diagnosis from August to December 2020 were invited to participate in this study (n = 297). Demographic and clinical characteristics and self-reported symptoms were ascertained prospectively using a detailed questionnaire administered at repeated phone interviews. RESULTS: A total of 226 individuals participated at baseline (226/297, 76% participation rate), of whom 170 participants had more than 3 months follow-up. Of these, 39% (n = 67/170, 95% confidence interval [CI] 32-37%) reported persistent symptoms (median [range] 168 [93-231] days) after the acute phase and 8% (n = 14/170, 95% CI 5-13%) reported severe persistent symptoms. The most prevalent symptoms were fatigue (17%) and smell (17%) and taste (14%) dysfunction. Long COVID was more common in people reporting daily medication use (odds ratio 2.34, 95% CI 1.02-5.37). CONCLUSION: Our results show that symptoms may take months to resolve, even among nonhospitalized individuals, with a mild illness in the acute phase. Continued monitoring for long COVID is needed to evaluate the added risk of a potential public health concern.
Assuntos
COVID-19 , COVID-19/complicações , COVID-19/epidemiologia , Teste para COVID-19 , Seguimentos , Humanos , Estudos Longitudinais , Prevalência , SARS-CoV-2 , Síndrome de COVID-19 Pós-AgudaRESUMO
Purpose: In this paper, we present age-standardized cancer incidence and mortality rates in the Faroe Islands. We also compare with the Nordic rates and show incidence rate ratios (IRR) and mortality rate ratios (MRR).Materials and methods: The Faroese cancer registry (FCR) was established in 1994, with incidence available from 1960 and mortality from 1983. The FCR is a part of the NORDCAN collaboration, where the different Nordic countries all report anonymized cancer data by standardized methods, ensuring comparability. Validation efforts revealed that 13% of cases had not been reported to the FCR from 2006 to 2019, emphasizing the need for continued validation efforts of cancer registries. After validation, we submitted the updated cancer cases to NORDCAN and now present this data, taken directly from the NORDCAN website (2019 data).Results: We found that the incidence of the summary group all cancers in the Faroe Islands increased from 1960 to 2019, while cancer mortality decreased from 1983 to 2019. Comparisons with Nordic rates showed significantly lower IRRs for cancer in all cancers, bladder and urinary tract, and skin cancer for both sexes, while IRR was lower for breast cancer in women and prostate cancer in men. Contrary, IRR was higher for rectum and kidney cancer in women and esophagus and testicular cancer in men. There was an increased MRR for cancer in female organs, bladder and urinary tract, and kidney cancer in women, and esophagus and pancreas cancer in men. In contrast, malignant hematopoietic diseases and melanoma in women had a lower MRR.Conclusions: Cancer incidence in the Faroe Islands was lower than in the other Nordic countries. Of particular interest, the incidence of testicular cancer saw a steep increase during the last 20 years, and an investigation into possible causes for this is needed.
Assuntos
Neoplasias Renais , Neoplasias Testiculares , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Mortalidade , Sistema de Registros , Fatores de Risco , Países Escandinavos e Nórdicos/epidemiologia , Taxa de Sobrevida , Neoplasias Testiculares/epidemiologiaRESUMO
The heredity of the malignant blood disorders, leukemias, lymphomas and myeloma, has so far been largely unknown. The present study comprises genealogical investigations of one hundred and twelve Scandinavian families with unrelated parents and two or more cases of malignant blood disease. For comparison, one large family with related family members and three hundred and forty-one cases of malignant blood disease from the Faroese population was included. The inheritance is non-Mendelian, a combination of genomic parental imprinting and feto-maternal microchimerism. There is significantly more segregation in maternal than in paternal lines, predominance of mother-daughter combinations in maternal lines, and father-son combinations in paternal lines. Chronic lymphocytic leukemia is the most frequent diagnosis in the family material, and chronic lymphocytic leukemia has a transgenerational segregation that is unique in that inheritance of susceptibility to chronic lymphocytic leukemia is predominant in males of paternal lines. Male offspring with chronic lymphocytic leukemia in paternal lines have a birth-order effect, which is manifest by the fact that there are significantly more male patients late in the sibling line. In addition, there is contravariation in chronic lymphocytic leukemia, i.e. lower occurrence than expected in relation to other diagnoses, interpreted in such a way that chronic lymphocytic leukemia remains isolated in the pedigree in relation to other diagnoses of malignant blood disease. Another non-Mendelian function appears in the form of anticipation, i.e. increased intensity of malignancy down through the generations and a lower age at onset of disease than otherwise seen in cases from the Cancer Registers, in acute lymphoblastic leukemia, for example. It is discussed that this non-Mendelian segregation seems to spread the susceptibility genes depending on the gender of the parents and not equally to all children in the sibling line, with some remaining unaffected by susceptibility i.e. "healthy and unaffected", due to a birth order effect. In addition, anticipation is regarded as a non-Mendelian mechanism that can amplify, «preserve¼ these vital susceptibility genes in the family. Perhaps this segregation also results in a sorting of the susceptibility, as the percentage of follicular lymphoma and diffuse large B-cell lymphoma is lower in the family material than in an unselected material. Although leukemias, lymphomas and myelomas are potentially fatal diseases, this non-Mendelian distribution and amplification hardly play any quantitative role in the survival of Homo sapiens, because these diseases mostly occur after fertile age.
Assuntos
Leucemia Linfocítica Crônica de Células B , Leucemia , Linfoma Folicular , Mieloma Múltiplo , Criança , Pai , Humanos , Leucemia/genética , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma Folicular/patologia , Masculino , LinhagemRESUMO
The Faroese population isolate harbors epidemiological and genetic characteristics that likely differ from outbred populations. This population-based register study found that the Faroese 2010-2020 crude incidence of amyotrophic lateral sclerosis (ALS) was 4.9/100,000 person-years (95% confidence interval [CI], 3.3-7.0) and the age- and sex-standardized incidence (US 2010 Census Population) was 4.1/100,000 person-years (95% CI, 2.7-6.0), which is a 68% increase from the 1987-2009 estimate. The 2020 crude prevalence was 9.5/100,000 (95% CI, 3.0-19.6) in a population of 52,912 inhabitants. Incidence and prevalence estimates of ALS in the Faroes are high and further research is warranted to uncover the genetic or environmental determinants of ALS in this population.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
Background: The demographic history of the Faroe Islands makes this isolated population - founded in the 9th century - interesting for genetic research. The goal of the FarGen project was to recruit individuals to the FarGen infrastructure to promote research into the genetic features of the Faroese people, and to develop a reference panel of population-specific variants. We aimed to recruit 1500 individuals. Participation was voluntary; participants had to donate a blood sample for whole-genome sequencing, and had to answer a questionnaire regarding sociodemographics, health, motivation and attitude towards participation in genetic research. Methods: A total of 1541 participants voluntarily joined the project, donated a blood sample and returned the questionnaire. Results: Answers from the questionnaire show that participants are, in general, European, have children, have a relatively high level of education, rate their health to be good, are willing to participate in future health-related research, and were motivated to sign up primarily to participate in research to help others and local research competency building. Conclusions: Overall, the initial cohort of the FarGen infrastructure comprises 3% of the Faroese population, and represents the general population well based on the collected sociodemographic data. However, there is an excess of women, and some geographic sub-regions and age groups are slightly underrepresented. We find the recruitment method with voluntary sign-up appropriate, and knowledge acquired through the first phase will aid the next phase of the project, with the aim of expanding the FarGen cohort with additional individuals, bio-specimens and body measurements in order to perform multifactorial analyses.
Assuntos
Atitude , Pesquisa em Genética , Criança , Dinamarca/epidemiologia , Feminino , Humanos , Inquéritos e QuestionáriosRESUMO
Close contacts of coronavirus disease (COVID-19) patients are at high risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. We assessed the seroprevalence of SARS-CoV-2-specific antibodies among quarantined close contacts of COVID-19 patients in the Faroe Islands. We invited quarantined close contacts of COVID-19 index patients identified during March 3-April 22, 2020, to participate in this study; 584 (81%) contacts consented and underwent serologic testing. Among the 584 participants, 32 (5.5%) were seropositive for total antibody against SARS-CoV-2. Household and young or elderly contacts had higher risk for seropositivity than other contacts. We found a secondary attack rate of 19.2%. Seroprevalence among close contacts was almost 10-fold higher than among the general population of the Faroe Islands. Regularly testing household close contacts of COVID-19 patients might help track the transmission of SARS-CoV-2.
Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Características da Família , Humanos , Quarentena , Estudos SoroepidemiológicosRESUMO
The Faroe Islands was one of the first countries in the Western Hemisphere to eliminate coronavirus disease (COVID-19). During the first epidemic wave in the country, 187 cases were reported between March 3 and April 22, 2020. Large-scale testing and thorough contact tracing were implemented early on, along with lockdown measures. Transmission chains were mapped through patient history and knowledge of contact with prior cases. The most common reported COVID-19 symptoms were fever, headache, and cough, but 11.2% of cases were asymptomatic. Among 187 cases, 8 patients were admitted to hospitals but none were admitted to intensive care units and no deaths occurred. Superspreading was evident during the epidemic because most secondary cases were attributed to just 3 infectors. Even with the high incidence rate in early March, the Faroe Islands successfully eliminated the first wave of COVID-19 through the early use of contact tracing, quarantine, social distancing, and large-scale testing.
Assuntos
COVID-19/epidemiologia , Busca de Comunicante , Distanciamento Físico , Quarentena , Adolescente , Adulto , Idoso , COVID-19/prevenção & controle , Criança , Pré-Escolar , Dinamarca/epidemiologia , Epidemias , Feminino , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
In the Faroe Islands, a clustering of amyotrophic lateral sclerosis (ALS) was observed on the geographically isolated island, Suðuroy. This study aims to estimate the frequency of familial ALS (fALS) in the Faroes including 43 patients diagnosed with ALS. Patients with fALS were identified through medical records and the Faroese Multi Generation Register. Firstly, fALS was recognized when occurring between first- or second-degree relatives. Secondly, families and individuals with fALS were recognized through pedigrees (≥3 cases within 3 generations). The prevalence of ALS was 3 times higher in Suðuroy compared to the nationwide prevalence. The frequency of fALS was at least 14% (n = 6) and mean survival time was 1.7 years shorter for fALS compared to sporatic ALS (p = 0.01. SD = 0.5, range 1.0-2.2). This study is suggestive of familial clustering in excess of expected for ALS and supports a genetic contribution to ALS in the Faroe Islands albeit environmental exposure within families cannot be excluded.
Assuntos
Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/genética , Dinamarca , Humanos , Linhagem , PrevalênciaRESUMO
BACKGROUND: Little is known about long-term recovery from coronavirus disease 2019 (COVID-19) disease, especially in nonhospitalized individuals. In this longitudinal study we present symptoms registered during the acute phase as well as long COVID (ie, long-lasting COVID-19 symptoms) in patients from the Faroe Islands. METHODS: All consecutive patients with confirmed reverse transcription-polymerase chain reaction testing from April to June 2020 were invited to participate in this study for the assessment of long COVID. Demographic and clinical characteristics and self-reported acute and persistent symptoms were assessed using a standardized detailed questionnaire administered at enrollment and at repeated phone interviews in the period 22 April to 16 August. RESULTS: Of the 180 participants (96.3% of the 187 eligible COVID-19 patients), 53.1% reported persistence of at least 1 symptom after a mean of 125 days after symptoms onset, 33.0% reported 1 or 2 symptoms, and 20.1% reported 3 or more symptoms. At the last follow-up, 46.9% were asymptomatic compared with 4.4% during the acute phase. The most prevalent persistent symptoms were fatigue, loss of smell and taste, and arthralgias. CONCLUSIONS: Our results show that it might take months for symptoms to resolve, even among nonhospitalized persons with mild illness course in the acute phase. Continued monitoring for long COVID is needed.
Assuntos
COVID-19 , COVID-19/complicações , Fadiga , Humanos , Estudos Longitudinais , SARS-CoV-2 , Síndrome de COVID-19 Pós-AgudaRESUMO
We conducted a nationwide study of the prevalence of severe acute respiratory syndrome coronavirus 2 infection in the Faroe Islands. Of 1,075 randomly selected participants, 6 (0.6%) tested seropositive for antibodies to the virus. Adjustment for test sensitivity and specificity yielded a 0.7% prevalence. Our findings will help us evaluate our public health response.
Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/sangue , SARS-CoV-2 , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Long-term collection of dried blood spot (DBS) samples through newborn screening may have retrospective and prospective advantages, especially in combination with advanced analytical techniques. This work concerns whether linked-reads may overcome some of the limitations of short-read sequencing of DBS samples, such as performing molecular phasing. We performed whole-exome sequencing of DNA extracted from DBS and corresponding whole blood (WB) reference samples, belonging to a trio with unaffected parents and a proband affected by primary carnitine deficiency (PCD). For the DBS samples we were able to phase >21% of the genes under 100 kb, >40% of the SNPs, and the longest phase block was >72 kb. Corresponding results for the WB reference samples was >85%, >75%, and >915 kb, respectively. Concerning the PCD causing variant (rs72552725:A > G) in the SLC22A5 gene we observe full genotype concordance between DBS and WB for all three samples. Furthermore, we were able to phase all variants within the SLC22A5 gene in the proband's WB data, which shows that linked-read sequencing may replace the trio information for haplotype detection. However, due to smaller molecular lengths in the DBS data only small phase blocks were observed in the proband's DBS sample. Therefore, further optimisation of the DBS workflow is needed in order to explore the full potential of DBS samples as a test bed for molecular phasing.
Assuntos
Teste em Amostras de Sangue Seco , Sequenciamento do Exoma , Genoma Humano , Polimorfismo de Nucleotídeo Único , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Malignant blood disorders depend on heritable susceptibility genes and occur in familial aggregations. We suggest a model of transgenerational segregation of the susceptibility genes based on the study of malignant blood disorders in Norwegian and Danish families with unrelated parents, and in the inbred Faroese population with related parents. This model, consisting of parental genomic imprinting and mother-son microchimerism, can explain the male predominance in most of the diseases, the predominance of affected parent-offspring when parents are not related, and the different modes of segregation in males and females. The model displays a specific pattern in the distribution of affected relatives for each diagnosis, viz. a characteristic distribution in the pedigrees of family members with malignant blood disorder related to the proband. Three such patterns, each reflecting a specific transgenerational passage, were identified: (1) alterations in the number of affected relatives in paternal lines alone, e.g. in patterns for probands with multiple myeloma; (2) alterations in the number of affected relatives in both paternal and maternal lines for probands with chronic lymphocytic leukemia; and (3) no alterations in the numbers of male and female affected relatives in the parental lines, e.g. for probands with some types of malignant lymphoma.