Xinjun Li1, Hauke Thomsen1,2,3, Kristina Sundquist1,4,5, Jan Sundquist1,4,5, Asta Försti1,2,6,7, Kari Hemminki1,2,8,9. 1. Center for Primary Health Care Research, Lund University, Malmö, Sweden. 2. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. 3. Genewerk GmbH, Heidelberg, Germany. 4. Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA. 5. Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan. 6. Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany. 7. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. 8. Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany. 9. Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605 Pilsen, Czech Republic.
Abstract
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.
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.
Authors: Ola Landgren; Eric A Engels; Ruth M Pfeiffer; Gloria Gridley; Lene Mellemkjaer; Jørgen H Olsen; Kimberly F Kerstann; William Wheeler; Kari Hemminki; Martha S Linet; Lynn R Goldin Journal: J Natl Cancer Inst Date: 2006-09-20 Impact factor: 13.506