Suchergebnisse

Childhood acute lymphoblastic leukemia (ALL) has an origin in the fetal period which may distinguish it from ALL diagnosed later in life. We wanted to test whether familial risks differ in ALL diagnosed in the very early childhood from ALL diagnosed later. The Swedish nation-wide family-cancer data were used until year 2016 to calculate standardized incidence ratios (SIRs) for familial risks in ALL in three diagnostic age-groups: 0-4, 5-34 and 35 + years. Among 1335 ALL patients diagnosed before age 5, familial risks were increased for esophageal (4.78), breast (1.42), prostate (1.40) and connective tissue (2.97) cancers and leukemia (2.51, ALL 7.81). In age-group 5-34 years, rectal (1.73) and endometrial (2.40) cancer, myeloma (2.25) and leukemia (2.00, ALL 4.60) reached statistical significance. In the oldest age-group, the only association was with Hodgkin lymphoma (3.42). Diagnostic ages of family members of ALL patients were significantly lower compared to these cancers in the population for breast, prostate and rectal cancers. The patterns of increased familial cancers suggest that BRCA2 mutations could contribute to associations of ALL with breast and prostate cancers, and mismatch gene PMS2 mutations with rectal and endometrial cancers. Future DNA sequencing data will be a test for these familial predictions. ; The study was supported by the European Union's Horizon 2020 research and innovation program, Grant No 856620, the Swedish Research Council (2016-01176; 2018-02400) and the ALF project grant, Region Skane/ Lund University, Sweden.

Background: Familial cancer can be defined through the occurrence of the same cancer in two or more family members. We describe a nationwide landscape of familial cancer, including its frequency and the risk that it conveys, by using the largest family database in the world with complete family structures and medically confirmed cancers. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for concordant cancer among first-degree relatives using the Swedish Cancer Registry from years 1958 through 2016. Results: Cancer risks in a 20–84 year old population conferred by affected parents or siblings were about two-fold compared to the risk for individuals with unaffected relatives. For small intestinal, testicular, thyroid and bone cancers and Hodgkin disease, risks were higher, five-to-eight-fold. Novel familial associations included adult bone, lip, pharyngeal, and connective tissue cancers. Familial cancers were found in 13.2% of families with cancer; for prostate cancer, the proportion was 26.4%. High-risk families accounted for 6.6% of all cancer families. Discussion/Conclusion: High-risk family history should be exceedingly considered for management, including targeted genetic testing. For the major proportion of familial clustering, where genetic testing may not be feasible, medical and behavioral intervention should be indicated for the patient and their family members, including screening recommendations and avoidance of carcinogenic exposure. ; Supported by the European Union's Horizon 2020 research and innovation program, grant No 856620 (Chaperon), the German Jose Carreras Leukemia Foundation, The Swedish Research Council, Jane and Aatos Erkko Foundation, Sigrid Juselius Foundation, Finnish Cancer Organizations, University of Helsinki and Helsinki University Central Hospital.

AbstractDiseases of the myoneural junction and muscle are disabling and some are life-threatening. Recent successes in the identification of the underlying genetic mechanisms have had profound implication for their diagnostics, treatment and classification. We define familial risks for siblings who were hospitalized for or deceased from diseases of the myoneural junction and muscle. A nationwide database on diseases of the myoneural junction and muscle was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register and the Causes of Death Register from years 1987 to 2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs by comparing to those whose siblings had no diseases of myoneural junction and muscle. Among a total of 2307 patients, myasthenia gravis, muscular dystrophy and myotonic disorders were commonest diagnoses. The sibling risks for these disease were 22, 190 and 198, respectively, when a sibling was diagnosed with any disease of the myoneural junction and muscle. The concordant SIRs, both siblings presenting the same disease, were 42 for myasthenia gravis, 737 for muscular dystrophy, 2000 for congenital myopathy, 1211 for myotonic disorder, 909 for periodic paralysis and 209 for unspecified myopathy. Only a few discordant sibling pairs were noted. The very high overall SIRs for the diseases of the myoneural junction and muscle imply that the sporadic forms of these diseases are relatively rare and these diseases are overwhelmingly heritable.

BACKGROUND: Head and neck cancers (HNCs) encompass a heterogeneous group of cancers between the mouth and larynx. Familial clustering in HNCs has been described, but how it influences individual sites and to which extent known risk factors, such as human papilloma virus (HPV) infection, may contribute is not well established. PATIENTS/METHODS: We employed standardized incidence ratios (SIRs) to estimate familial risks for HNC with same (concordant) and different (discordant) cancers among first-degree relatives using data from the Swedish Cancer Registry from 1958 to 2018. RESULTS: Incidence for male and female oropharyngeal cancer increased close to four-fold in the past 39 years. Familial HNC was found in 3.4% of the study population, with an overall familial SIR of 1.78. Patients with concordant nasopharyngeal cancer showed a high risk of 23.97, followed by hypopharyngeal cancer (5.43). The husbands of wives with cervical cancer had an increased risk of oropharyngeal cancer. DISCUSSION/CONCLUSION: Nasopharyngeal cancers lacked associations with lifestyle or HPV associated cancers, suggesting a role for germline genetics, which was also true for the high-risk families of three HNC patients. In the Swedish population with low smoking levels, HPV is becoming a dominant risk factor, emphasizing the need for sexual hygiene and HPV vaccination. ; The study was supported by the European Union's Horizon 2020 research and innovation program, grant no. 856620; the Swedish Research Council (2020-01175; 2018-02400); and the ALF project grant, Region Skane/Lund University, Sweden.

Background: Pernicious anemia (PA) is an autoimmune disease (AID) which is caused by lack of vitamin B12 (cobalamin) due to its impaired uptake. PA is a multifactorial disease which is associated with a number of other AID comorbidities and which is manifested as part of autoimmune polyglandular syndrome. Due to the shortage of family studies on PA, we planned to address the problem by assessing familial risks for concordant PA between family members and for discordant PA in families of other AID patients. Methods: We collected data on patients diagnosed with AIDs from the Swedish hospitals and family data from a population register. We calculated standardized incidence ratios (SIRs) in families for concordant and discordant risks. Results: The number of PA patients in the offspring generation (for which the familial risk was calculated) was 7701; 278 (3.6%) patients had a family history of PA. The population prevalence of PA was 0.9/1000. The familial risk for PA was 3.88 when any first-degree relative was the proband, equal for men and women. The familial risk was two times higher between siblings than between offspring and parents which may be due to complex genetic background. Associations of PA with 14 discordant AIDs were significant; these included some AIDs that have previously been described as comorbidities in PA patients and several yet unreported associations, including rheumatoid arthritis and other AIDs. Conclusions: The familial risks for PA were high suggesting multifactorial genetic etiology. The results call for further population-level studies to unravel mechanisms of familial PA which may help to understand the etiology of this disease. ; is study was supported by the European Union's Horizon 2020 Research and Innovation Program (grant no. 856620), Swedish Research Council (2016-01176 (to Jan Sundquist) and 2018-02400 (to Kristina Sundquist)), Swedish Heart- Lung Foundation, and ALF project grant, Lund University, Sweden.

Autoimmune hepatitis (AH) and primary biliary cirrhosis (PBC) are autoimmune diseases (AIDs) targeting cellular components of the liver. Being rare diseases, limited data are available about familial risks among these AIDs (concordant) or between them and other AIDs (discordant). We aimed to carry out an unbiased study on these AIDs based on medically diagnosed patients. We collected data on patients diagnosed in Swedish hospitals with AH, PBC and other AIDs and calculated familial standardized incidence ratios (SIRs) for concordant and discordant familial relative risks. The number of AH patients was 6,269, of whom 43.0% were male; patient numbers for PBC were 4,269, with 17.8% males. AH accounted for 0.8% and 0.6% of all hospitalized AIDs in Sweden. For AH only the familial risk between siblings was significant (3.83). For PBC the risks for offspring of parents (9.05) and siblings (10.88) were high, but only risk for females was significant. Spousal risks were very high, 5.91 and 6.07 for AH. Risk for AH was 2.21 in families of PBC, and it was 2.47 for PBC in families of AH patients. Among other AIDs, 14 showed a significant association with AH, compared to 16 AIDs with PBC. The surprising finding in this nation-wide family study on medically diagnosed patients was the high risk for AH (6.0) between spouses, which exceed the risk between siblings, suggesting the existence of strong environmental risk factors. AH and PBC were associated with multiple other AIDs. The results call attention to environmental factors in AID etiology which should also be in focus in taking anamnestic data from patients. ; The study was supported by the European Union's Horizon 2020 research and innovation programme, grant No 856620. HT receives salary from GeneWerk GmbH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Genetic and family studies have indicated that Graves disease and Hashimoto thyroiditis have a heritable component which appears to be shared to some extend also with some other autoimmune diseases (AIDs). In the present nation-wide study we describe familial risk for Graves disease and Hashimoto thyroiditis identified from the Swedish Hospital Discharge Register (years 1964 through 2012) and the Outpatient Register (2001 through 2012). Family relationships were obtained from the Multigeneration Register and cancers from the Cancer Registry. Familial standardized incidence ratios (SIRs) were calculated for 29,005 offspring with Graves disease and for 25,607 offspring with Hashimoto thyroiditis depending on any of 43 AIDs in parents or siblings. The concordant familial risks for Graves disease and Hashimoto thyroiditis were 3.85 and 4.75, higher for men than for women. The familial risks were very high (11.35, Graves and 22.06, Hashimoto) when both a parent and a sibling were affected. Spousal familial risks were higher for Hashimoto thyroiditis (1.98/1.93) than for Graves disease (1.48/1.50). For Graves disease, 24 discordant AIDs showed a significant association; for Hashimoto thyroiditis, 20 discordant associations were significant. All significant discordant associations were positive for the two thyroid AIDs, with the exception of Hashimoto thyroiditis with Reiter disease. Overall 8 associations were significant only for Graves disease and 6 Hashimoto thyroiditis. The overall high concordant familial risks for Graves disease and Hashimoto thyroiditis suggest a strong genetic contribution to the familial risk. Significant familial associations among more than half of the 43 AIDs attest to the extensive polyautoimmunity among thyroid AIDs. ; The study was supported by the European Union's Horizon 2020 research and innovation programme, grant No 856620.

BackgroundAlthough studies have shown associations between neighbourhood quality and chronic disease outcomes, such associations are potentially confounded by the selection of different types of people into different neighbourhood environments. We sought to identify the causal effects of neighbourhood deprivation on type 2 diabetes risk, by comparing refugees in Sweden who were actively dispersed by government policy to low-deprivation, moderate-deprivation, or high-deprivation neighbourhoods.MethodsIn this quasi-experimental study, we analysed national register data for refugees who arrived in Sweden aged 25-50 years, at a time when the government policy involved quasi-random dispersal of refugees to neighbourhoods with different levels of poverty and unemployment, schooling, and social welfare participation. Individuals in our sample were assigned to a neighbourhood categorised as high deprivation (≥1 SD above the mean), moderate deprivation (within 1 SD of the mean), or low deprivation (≥1 SD below the mean). The primary outcome was new diagnosis of type 2 diabetes between Jan 1, 2002, and Dec 31, 2010. We used multivariate logistic and linear regressions to assess the effects of neighbourhood deprivation on diabetes risk, controlling for potential confounders affecting neighbourhood assignment and assessing effects of cumulative exposure to different neighbourhood conditions.FindingsWe included data for 61 386 refugees who arrived in Sweden during 1987-91 and who were assigned to one of 4833 neighbourhoods. Being assigned to an area deemed high deprivation versus low deprivation was associated with an increased risk of diabetes (odds ratio [OR] 1·22, 95% CI 1·07-1·38; p=0·001). In analyses that included fixed effects for assigned municipality, the increased diabetes risk was estimated to be 0·85 percentage points (95% CI -0·030 to 1·728; p=0·058). Neighbourhood effects grew over time such that 5 years of additional exposure to high-deprivation versus low-deprivation neighbourhoods was associated with a 9% increase in diabetes risk.InterpretationThis study makes use of a pre-existing governmental natural experiment to show that neighbourhood deprivation increased the risk of diabetes in refugees in Sweden. This finding has heightened importance in the context of the current refugee crisis in Europe.FundingUS National Heart, Lung, and Blood Institute, US National Center for Advancing Translational Sciences, US National Institute on Minority Health and Health Disparities, Swedish Research Council.