| 1. |
- Hemminki, Kari, et al.
(författare)
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The epidemiology of Graves' disease: Evidence of a genetic and an environmental contribution.
- 2010
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 34, s. 307-313
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Tidskriftsartikel (refereegranskat)abstract
- Previous family and twin studies have indicated that Graves' disease has a heritable component. Family studies have also shown that some autoimmune disease cluster in families and genetic studies have been able to show shared susceptibility genes. In the present nation-wide study we describe familial risk for Graves' disease among parents and offspring, singleton siblings, twins and spouses with regard to age of onset, gender and number and type of affected family members. Additionally familial association of Graves' disease with any of 33 other autoimmune and related conditions was analyzed. The Swedish Multigeneration Register on 0-75-year-old subjects was linked to the Hospital Discharge Register from years 1987-2007. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized for Graves' disease compared to those whose relatives were unaffected. The total number of hospitalized Graves' patients was 15,743. Offspring with an affected family member constituted 3.6% of all patients among offspring. The familial SIR was 5.04 for individuals whose sibling was affected but it increased to 310 when two or more siblings were affected; the SIR in twins was 16.45. Familial risks were higher for males than for females. The SIR was increased to 6.22 or 30.20 when parental age was limited to 50 or 20 years, respectively. Graves' disease associated with 19 other autoimmune and related conditions, including Addison's disease, type 1 diabetes mellitus, Hashimoto/hypothyroidism, pernicious anemia, polymyositis/dermatomyositis, myasthenia gravis, discoid lupus erythematosus and localized scleroderma. Remarkably, there was a high disease concordance of 2.75 between spouses. The clustering between spouses suggests environmental effects on Graves' disease which may contribute to the observed gender effects. The demonstrated high risks should be considered in clinical counseling and in prevention plans.
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| 2. |
- Hemminki, Kari, et al.
(författare)
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Cancer risk in amyloidosis patients in Sweden with novel findings on non-Hodgkin lymphoma and skin cancer
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 25:2, s. 511-518
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic amyloidosis (SSA) is a common form of amyloidosis but it remains often unnoticed because of the slow progression in old patients. The cause for SSA is the accumulation of wild-type transthyretin amyloids in critical tissues. We provide here data showing that SSA may be associated with old-age non-Hodgkin lymphoma.Systemic amyloidoses include immunoglobulin light chain (AL) amyloidosis, serum amyloid (AA)-related amyloidosis and senile systemic amyloidosis (SSA). AL amyloidosis is associated with myeloma, and we showed recently that transthyretin-related hereditary amyloidosis was related to non-Hodgkin lymphoma (NHL). In SSA, amyloids constitute wild-type transthyretin. We wanted to analyze cancer risks in amyloidosis, particularly in SSA. Nonhereditary amyloidosis patients were identified from the Swedish Hospital Discharge and Outpatients Registers from years 1997 through 2010. Their cancer risk was assessed based on the Swedish Cancer Registry using standardized incidence ratio (SIR) between amyloidosis patients and the remaining population. To gain information about amyloidosis subtypes, we used the Swedish Prescribed Drug Register from years 2005 through 2010 to find out the specific medication prescribed. Among 1400 identified amyloidosis patients, cancer risk was increased for myeloma, NHL and squamous cell skin cancer. Myeloma and skin cancers were diagnosed 7-8 years earlier than in the population, whereas NHL was diagnosed in elderly patients. The SIR was 204 for myeloma in patients who received AL amyloidosis medication, and it was 17.22 in patients receiving rheumatoid arthritis medication, suggesting AA amyloidosis. In remaining patients, including SSA, NHL risk was 14.78, including lymphoplasmacytic lymphoma and Waldenstrom macroglobulinemia (51.41) and diffuse large B-cell lymphoma (18.69). In these patients, endometrial cancer (7.04) and cancer of unknown primary site (6.56) were also increased. SSA is likely to be a main cause of NHL in the elderly population. The present findings suggest a novel mechanism for amyloidosis-related cancer, highlighting the role of chronic stimulation by amyloid.
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| 3. |
- Hemminki, Kari, et al.
(författare)
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Familial Association of Inflammatory Bowel Diseases With Other Autoimmune and Related Diseases
- 2010
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 105:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Familial risk estimates are useful for genetic counseling, etiological understanding, and design of gene identification studies. We wanted to estimate the associations of ulcerative colitis (UC) and Crohn's disease (CD) with 32 autoimmune and related diseases among parents and offspring, singleton siblings, twins, and spouses. METHODS: The Multigeneration Register in Sweden provides reliable access to information on families among 11.5 million individuals throughout the last century. The diseases in individual family members were obtained through linkage to the Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95 % confi dence intervals were calculated as relative risks for UC/CD in family members of patients diagnosed with any of the 34 diseases compared with those lacking affected family members through years 1964-2004. RESULTS: Among a total of 441,642 patients diagnosed with autoimmune and related conditions, 25,846 were diagnosed with UC and 18,885 with CD. Familial cases amounted to 5.4 % of all UC patients and 6.5 % of CD patients. SIR for UC was 3.9 (95% confidence interval 3.5 - 4.3) in offspring of affected parents, 4.6 (3.0-7.4) in siblings, 10.4 (6.5-15.8) in families of affected parents and siblings, and 6.3 (1.9-17.7) for monozygotic twins. The respective SIRs for CD were 6.0 (5.4-6.7), 6.3 (4.1-9.8), 34.0 (24.9-45.3), and 23.4 (10.1-51.1). All discordant associations, i. e., those between CD and other diseases, were also found for UC, including ankylosing spondylitis, asthma, polymyalgia rheumatica, psoriasis, and sarcoidosis. For UC, six additional associations were observed. No correlations between specifi c diseases were found among spouses, but between UC or CD and any disease it was 1.1 (1.0-1.1). CONCLUSIONS: The concordant familial risks for UC and CD were lower than those commonly cited. Both diseases are associated with several autoimmune and related diseases, suggesting genetic sharing. Am J Gastroenterol 2010; 105: 139- 147; doi: 10.1038/ ajg. 2009.496; published online 25 August 2009
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| 4. |
- Hemminki, Kari, et al.
(författare)
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Familial Risks for Type 2 Diabetes in Sweden
- 2010
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:2, s. 293-297
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - Our aim was to characterize familial risks for type 2 diabetes by the type and number of affected family members, including half-siblings, adoptees, and spouses, to quantify risks and estimate the contribution of environmental effect. RESEARCH DESIGN AND METHODS - Families were identified from the Multigeneration Register, and type 2 diabetic patients were obtained from the Hospital Discharge Register. Standardized incidence ratios were calculated for offspring with type 2 diabetes whose family members were hospitalized for type 2 diabetes at ages >39 years compared With those lacking affected family members. RESULTS - The number of hospitalized type 2 diabetic patients was 157,549. Among 27,895 offspring, 27.9% had a parent or sibling also hospitalized for type 2 diabetes. The familial relative risk (RR) ranged from 2.0 to >30, depending on the number and type of probands. The highest RRs of type 2 diabetes were found in individuals who had at least two siblings affected by type 2 diabetes, irrespective of the parental disease. Adoptees showed no risk from adopted parents. CONCLUSIONS - The Study, the largest yet published, showed that familial RRs varied by the number and type Of affected family member. However, much Of the familial clustering remains yet to be genetically explained. The high risk should be recognized in clinical genetic counseling. The data from adoptees confirmed the genetic basis Of the familial associations, but those from half siblings and Spouses Suggested that a smaller part of familial Clustering may be accounted for by environmental factors.
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| 5. |
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| 6. |
- Hemminki, Kari, et al.
(författare)
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Incidence and survival in non-hereditary amyloidosis in Sweden
- 2012
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 12:974
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyloidosis is a heterogeneous disease caused by deposition of amyloid fibrils in organs and thereby interfering with physiological functions. Hardly any incidence data are available and most survival data are limited to specialist clinics. Methods: Amyloidosis patients were identified from the Swedish Hospital Discharge and Outpatients Registers from years 2001 through 2008. Results: The incidence of non-hereditary amyloidosis in 949 patients was 8.29 per million person-years and the diagnostic age with the highest incidence was over 65 years. Secondary systemic amyloidosis showed an incidence of 1 per million and a female excess and the largest number of subsequent rheumatoid arthritis deaths; the median survival was 4 years. However, as rheumatoid arthritis deaths also occurred in other diagnostic subtypes, the incidence of secondary systemic amyloidosis was likely to be about 2.0 per million. The median survival of patients with organ-limited amyloidosis was 6 years. Most myeloma deaths occurred in patients diagnosed with unspecified or 'other' amyloidosis. These subtypes probably accounted for most of immunoglobulin light chain (AL) amyloidosis cases; the median survival time was 3 years. Conclusions: The present diagnostic categorization cannot single out AL amyloidosis in the Swedish discharge data but, by extrapolation from myeloma cases, an incidence of 3.2 per million could be ascribed to AL amyloidosis. Similarly, based on rheumatoid arthritis death rates, an incidence of 2.0 could be ascribed to secondary systemic amyloidosis.
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| 7. |
- Hemminki, Kari, et al.
(författare)
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Incidence of hereditary amyloidosis and autoinflammatory diseases in Sweden: endemic and imported diseases
- 2013
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyloidoses are a heterogeneous group of progressive diseases caused by tissue deposition of misfolded proteins. According to the International Classification of Diseases, hereditary amyloidosis is divided into neuropathic and non-neuropathic forms. In Sweden, neuropathic heredofamilial amyloidosis has been identified as familial amyloidotic polyneuropathy (FAP), a fatal disease that is treated by liver transplantation. The non-neuropathic form includes familial autoinflammatory diseases. As no incidence data on these hereditary diseases are available and as even diagnostic data on non-neuropathic forms are lacking we determined the incidence of these diseases and characterized non-neuropathic conditions. Methods: Patients were identified using data from the Swedish Hospital Discharge Register and from the Outpatient Register for 2001 through 2008. All patients discharged with hereditary amyloidosis diagnoses were included and standardized incidence rates were calculated. Results: Non-neuropathic disease was diagnosed in 210 patients, with an incidence of 2.83 per million. FAP was diagnosed in 221 patients, with an incidence of 2.02 per million. Two northern provinces that are home to 5% of the Swedish population accounted for 77% of FAP cases; the incidence in one of them, West Bothnia, was 100 times that in the rest of Sweden. Approximately 98% of non-neuropathic disease patients were immigrants, most of whom were from the Eastern Mediterranean area. Young Syrian descendants had the highest incidence rate, which was over 500-fold higher than that in individuals with Swedish parents. Even the early onset of these conditions identified them as familial autoinflammatory diseases. Conclusions: FAP cases were highly concentrated in the two northernmost provinces. Non-neuropathic familial autoinflammatory diseases were of early-onset and immigrant origin most likely related to periodic fever syndromes. Paradoxically, FAP has remained endemic, in spite of population movements within the country, while familial autoinflammatory diseases, with an incidence exceeding that of FAP, were brought into the country as a result of immigration mainly from the Eastern Mediterranean area.
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| 8. |
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| 9. |
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| 10. |
- Hemminki, Kari, et al.
(författare)
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Obesity and familial obesity and risk of cancer.
- 2011
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Ingår i: European Journal of Cancer Prevention. - 1473-5709. ; 20, s. 438-443
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with a risk of at least 20 different cancers. We aimed at defining cancer risks in prospectively recruited patients with a novel subgroup, those with a family history of obesity. We defined a cohort of 30 020 patients who had been hospitalized since 1964. Cancer risks in these patients were followed through 2006. Standardized incidence ratios were calculated for cancer using those not hospitalized for obesity as a reference population. We could also identify persons who had been hospitalized for type 2 diabetes. A total of 1721 patients were diagnosed with cancer after hospitalization for obesity, showing an increased risk for 12 cancers and a decrease for breast cancer. The largest increases were found for nervous system hemangioma (13.64, 95% confidence interval 2.57-40.37) and other male genital (3.94, 1.24-9.26), bone (3.41, 1.23-7.47), small intestinal (2.93, 1.60-4.93), kidney (2.46, 1.97-3.02), and endometrial (2.32, 2.01-2.66) cancers. Among endocrine cancers, adrenal tumors showed the highest risk, of 3.74 (1.86-6.72). The overall risk was 1.19 (1.13-1.25). Family history of obesity was associated with formerly unrecognized increased risks of gallbladder and colon cancers and ocular melanoma. Cancer risks in this relatively young obese population differed quantitatively from those found after type 2 diabetes. The novel findings included rare and relatively benign tumors, probably found in endocrinological and other medical examinations for obesity and related conditions. Similarly, male genital cancer may be related to sexual behavior, and bone cancers, found in old individuals, could be related to propensity for fractures.
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