| 1. |
- Blunk, Inga, et al.
(författare)
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Genomic imprinting analyses identify maternal effects as a cause of phenotypic variability in type 1 diabetes and rheumatoid arthritis
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Imprinted genes, giving rise to parent-of-origin effects (POEs), have been hypothesised to affect type 1 diabetes (T1D) and rheumatoid arthritis (RA). However, maternal effects may also play a role. By using a mixed model that is able to simultaneously consider all kinds of POEs, the importance of POEs for the development of T1D and RA was investigated in a variance components analysis. The analysis was based on Swedish population-scale pedigree data. With P = 0.18 (T1D) and P = 0.26 (RA) imprinting variances were not significant. Explaining up to 19.00% (± 2.00%) and 15.00% (± 6.00%) of the phenotypic variance, the maternal environmental variance was significant for T1D (P = 1.60 × 10−24) and for RA (P = 0.02). For the first time, the existence of maternal genetic effects on RA was indicated, contributing up to 16.00% (± 3.00%) of the total variance. Environmental factors such as the social economic index, the number of offspring, birth year as well as their interactions with sex showed large effects.
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| 2. |
- Chen, Tianhui, et al.
(författare)
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Risk of Second Primary Cancers in Multiple Myeloma Survivors in German and Swedish Cancer Registries.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- We aimed at investigating the distribution and risk of second primary cancers (SPCs) in multiple myeloma (MM) survivors in Germany and Sweden to provide etiological understanding of SPCs and insight into their incidence rates and recording practices. MM patients diagnosed in 1997-2010 at age ≥15 years were selected from the Swedish (nationwide) and 12 German cancer registries. Standardized incidence ratios (SIRs) were used to assess risk of a specific SPC compared to risk of the same first cancer in the corresponding background population. Among 18,735 survivors of first MM in Germany and 7,560 in Sweden, overall 752 and 349 SPCs were recorded, respectively. Significantly elevated SIRs of specific SPCs were observed for acute myeloid leukemia (AML; SIR = 4.9) in Germany and for kidney cancer (2.3), AML (2.3) and nervous system cancer (1.9) in Sweden. Elevated risk for AML was more pronounced in the earlier diagnosis period compared to the later, i.e., 9.7 (4.2-19) for 1997-2003 period versus 3.5 (1.5-6.9) for 2004-2010 in Germany; 3.8 (1.4-8.3) for 1997-2003 versus 2.2 (0.3-7.8) for 2004-2010 in Sweden. We found elevated risk for AML for overall, early diagnosis periods and longer follow-up times in both populations, suggesting possible side effects of treatment for MM patients.
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| 3. |
- Hemminki, Kari, et al.
(författare)
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Age-Dependent Metastatic Spread and Survival : Cancer of Unknown Primary as a Model
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- In order to describe a novel approach for the clinical study of metastases, we provide here age-specific incidence and survival data for cancer of unknown primary (CUP). Metastases in various organs are found at CUP diagnosis, which have implications for prognosis, and we hypothesize similar prognostic implications for metastases found at diagnosis of primary cancers. We identified 33,224 CUP patients from the Swedish Cancer Registry and calculated incidence rates (IRs) for CUP development. Cox proportional hazards regression models were performed to estimate hazard ratios (HRs) for relative survival in CUP patients compared to the general population. In age-group specific analyses, a maximal IR was reached at age 85-89 years, followed by a marked decline to age 90+ (7-fold in men and 3-fold in women). The overall HR for relative survival declined systematically by age. CUP may be applied as an epidemiological age-incidence model for cancer metastases providing evidence in line with autopsy data that the metastatic potential, as shown by the incidence of CUP, appears to weaken markedly at age 85 years, depending on metastatic locations. The relative death rates were highest among young patients, which was probably entirely due to the low death rates in young background population.
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| 4. |
- Hemminki, Kari, et al.
(författare)
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Familial Risks between Urolithiasis and Cancer
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Author(s). Urolithiasis (UL, urinary tract stone disease) has been reported to increase subsequent cancers in the urinary tract. Recently, we showed data that surveillance bias may be an important confounder in the reported associations. In the present approach we want to address the question of possible cancer risk posed by UL mechanistically. Both UL and cancer have strong genetic components and we hypothesize that familial association between UL and cancer may be plausible. We thus assess familial risks between UL and cancer, hoping to find an explanation why UL may pose a risk of cancer. UL patients were identified from hospital inpatient and outpatient records and they were organized in families based on the Multigeneration Register into which also national cancer data were linked. Standardized incidence ratios were calculated for cancer in the offspring generation when parents were diagnosed with UL, and conversely for UL when parents were diagnosed with cancer. Familial risks between UL and cancer were generally small and inconsistent providing no convincing support of genetic sharing between UL and cancer. However, bladder UL was associated weakly with prostate cancer, and ureter and bladder UL were associated with salivary gland cancer. Potential mechanisms for these findings are proposed.
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| 5. |
- Hemminki, Kari, et al.
(författare)
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Location of metastases in cancer of unknown primary are not random and signal familial clustering.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer of unknown primary (CUP) is a fatal disease diagnosed through metastases. It shows intriguing familial clustering with certain defined primary cancers. Here we examine whether metastatic location in CUP patients is related to primary non-CUP cancers in relatives based on the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for CUP patients defined by metastatic location depending on cancer in their first degree relatives. SIRs for CUP were high in association with liver (3.94), ovarian (3.41), lung (2.43) and colorectal cancers (1.83) in relatives. The SIR was 1.63 for CUP with metastases in the abdomen when a relative was diagnosed with ovarian cancer. CUP with liver metastases associated with liver (1.44) cancer in relatives. CUP with head and neck region metastases associated with relatives' esophageal (2.87) cancer. CUP metastases in the thorax associated with a relative's cancers in the upper aerodigestive tract (2.14) and lung (1.74). The findings, matching metastatic location in CUP and primary cancer in relatives, could be reconciled if these cases of CUP constitute a phenotypically modified primary lacking tissue identification, resulting from epitope immunoediting. Alternatively, CUP metastases arise in a genetically favored tissue environment (soil) promoting growth of both primary cancers and metastases (seeds).
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| 6. |
- Hemminki, Kari, et al.
(författare)
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Subsequent Type 2 Diabetes in Patients with Autoimmune Disease.
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Immunological data show that type 2 diabetes (T2D) manifests autoimmune features. We wanted to test the association epidemiologically by assessing subsequent diagnosis of T2D following diagnosis of autoimmune disease (AId) and subsequent AId after T2D in the same individuals. Patients were identified from three Swedish health databases. A total of 32 different AId were included. Standardized incidence ratios (SIRs) were calculated for T2D diagnosis in patients with previously diagnosed AId and compared to those without a previous AId. Among a total of 757,368 AId patients, 15,103 were diagnosed with T2D, giving an overall SIR for T2D of 1.66. T2D risks were increased after 27 AIds; the highest SIRs were noted for chorea minor (8.00), lupoid hepatitis (5.75), and Addison disease (2.63). T2D was increased after 27 of 32 AIds but we were unable to control for factors such as obesity and smoking. However, the clearly increased risks for T2D in most types of AId patients, and in reverse order increased risks for AId after T2D, do not support an overall confounding by life-style factors. Mechanistic links shared by T2D, AId and life-style factors such as obesity, perhaps through chronic inflammation, may drive autoimmune activation of T2D and many AIds.
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| 7. |
- Hemminki, Kari, et al.
(författare)
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Surveillance Bias in Cancer Risk after Unrelated Medical Conditions : Example Urolithiasis
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- We analysed cancer risks in patients with urinary tract stones but some features of the generated results alarmed us about possible surveillance bias, which we describe in this report. We used nationwide Swedish hospital records to identify patients with urinary tract stones (N = 211,718) and cancer registration data for cancer patients for years 1987 to 2012. Standardized incidence ratios (SIRs) for cancer were calculated after the last medical contact for urinary tract stones. All cancers were increased after kidney (SIR 1.54, 95%CI: 1.50-1.58), ureter (1.44, 1.42-1.47), mixed (1.51, 1.44-1.58) and bladder stones (1.63, 1.57-1.70). The risk of kidney cancer was increased most of all cancers after kidney, ureter and mixed stones while bladder cancer was increased most after bladder stones. All SIRs decreased steeply in the course of follow-up time. Tumour sizes were smaller in kidney cancer and in situ colon cancers were more common in patients diagnosed after urinary tract stones compared to all patients. The results suggest that surveillance bias influenced the result which somewhat surprisingly appeared to extend past 10 years of follow-up and include cancers at distant anatomical sites. Surveillance bias may be difficult to avoid in the present type of observational studies in clinical settings.
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| 8. |
- Hemminki, Kari, et al.
(författare)
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The Incidence of Senile Cataract and Glaucoma is Increased in Patients with Plasma Cell Dyscrasias : Etiologic Implications
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Plasma cell dyscrasias, including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), Waldenström macroglobulinemia (WM) and light chain AL amyloidosis, are characterized by clonal expansion of plasma cells which produce a vast amount of an immunoglobulin-derived M-protein. We noted that MGUS diagnosis often coincided with diagnoses of senile cataract and glaucoma and tested the associations of MGUS, MM, WM and AL amyloidosis with subsequent eye diseases identified from the Swedish patient registers between 1997 and 2012. Standardized incidence ratios (SIRs) for senile cataract was significantly increased to 1.80 after MGUS, 1.70 after MM, 1.85 after WM and 2.31 after AL amyloidosis. The SIR for glaucoma was 1.60 after MGUS, 1.76 after WM and 2.18 after AL amyloidosis. All SIRs decreased systematically from age below 60 years to over 79 years, but most risks were also significant in age group over 79 years. The M-protein and the related increase in blood viscosity could be a novel etiologic discovery for these common eye diseases. As MGUS prevalence is around 3% at 60 years and close to 10% at age over 80 years, its contribution to the eye disease burden is expected to be remarkably high.
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| 9. |
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| 10. |
- Jansåker, Filip, et al.
(författare)
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Neighborhood deprivation and coronary heart disease in patients with bipolar disorder
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to study the potential effect of neighborhood deprivation on incident and fatal coronary heart disease (CHD) in patients with bipolar disorder. This was a nationwide cohort study which included all adults aged 30 years or older with bipolar disorder (n = 61,114) in Sweden (1997–2017). The association between neighborhood deprivation and the outcomes was explored using Cox regression analysis, with hazard ratios (HRs) and 95% confidence intervals (CIs). Patients with bipolar disorder living in neighborhoods with high or moderate levels of deprivation were compared with those living in neighborhoods with low deprivation scores. There was an association between level of neighborhood deprivation and incident and fatal CHD among patients with bipolar disorder. The HRs were 1.24 (95% CI 1.07–1.44) for men and 1.31 (1.13–1.51) for women for incident CHD among patients with bipolar disorder living in high deprivation neighborhoods compared to those from low deprivation neighborhoods, after adjustments for potential confounders. The corresponding HR for fatal CHD were 1.35 (1.22–1.49) in men and 1.30 (1.19–1.41) in women living in high deprivation neighborhoods. Increased incident and fatal CHD among patients with bipolar disorder living in deprived neighborhoods raises important clinical and public health concerns.
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