Kari Hemminki1,2, Otto Hemminki3,4, Asta Försti1,2, Kristina Sundquist2,5, Jan Sundquist2,5, Xinjun Li2. 1. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 2. Center for Primary Health Care Research, Lund University, Malmö, Sweden. 3. Department of Urology, Helsinki University Hospital, Helsinki, Finland. 4. Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 5. Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
OBJECTIVE: To assess detailed familial risks for medically diagnosed urolithiasis (UL, urinary tract stone disease) based on nationwide hospital and population records. PATIENTS/SUBJECTS AND METHODS: Subjects were identified from the Swedish Multigeneration Register in which there were 211 718 patients with UL. Standardised incidence ratios (SIRs) were calculated by comparison to individuals without a family history of UL. RESULTS: The highest familial SIRs were invariably found for the same (concordant) type of UL: 2.18 for kidney, 2.20 for ureter, and 1.93 for bladder. SIRs increased from 1.84, when one parent was affected, to 3.54 when both parents were affected, which was a multiplicative interaction. The SIR was 1.79 when one sibling was affected but it increased to 24.91 when two siblings were affected. Such excessive risks (5.2% of familial cases) are probably explained by high-penetrant genes. A low SIR of 1.29 between spouses suggested a minor contribution by shared environmental factors on the familial risk. CONCLUSIONS: The results point to underlying genetic causes for the observed familial clustering and establish the genetic landscape of UL. Family histories should be taken in UL diagnostics and prevention could follow guidelines recommended for recurrent UL.
OBJECTIVE: To assess detailed familial risks for medically diagnosed urolithiasis (UL, urinary tract stone disease) based on nationwide hospital and population records. PATIENTS/SUBJECTS AND METHODS: Subjects were identified from the Swedish Multigeneration Register in which there were 211 718 patients with UL. Standardised incidence ratios (SIRs) were calculated by comparison to individuals without a family history of UL. RESULTS: The highest familial SIRs were invariably found for the same (concordant) type of UL: 2.18 for kidney, 2.20 for ureter, and 1.93 for bladder. SIRs increased from 1.84, when one parent was affected, to 3.54 when both parents were affected, which was a multiplicative interaction. The SIR was 1.79 when one sibling was affected but it increased to 24.91 when two siblings were affected. Such excessive risks (5.2% of familial cases) are probably explained by high-penetrant genes. A low SIR of 1.29 between spouses suggested a minor contribution by shared environmental factors on the familial risk. CONCLUSIONS: The results point to underlying genetic causes for the observed familial clustering and establish the genetic landscape of UL. Family histories should be taken in UL diagnostics and prevention could follow guidelines recommended for recurrent UL.
Authors: Kari Hemminki; Otto Hemminki; Anni I M Koskinen; Asta Försti; Kristina Sundquist; Jan Sundquist; Xinjun Li Journal: BMC Nephrol Date: 2018-07-03 Impact factor: 2.388