| 1. |
- 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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| 2. |
- 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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| 3. |
- Hemminki, Kari, et al.
(författare)
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Origin of B-cell neoplasms in autoimmune disease
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation.
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| 4. |
- Hemminki, Kari, et al.
(författare)
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Risk of Cancer of Unknown Primary after Hospitalization for Autoimmune Diseases.
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 137:12, s. 2885-2895
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Tidskriftsartikel (refereegranskat)abstract
- Cancer of unknown primary (CUP) is a heterogeneous syndrome diagnosed at metastatic sites. The etiology is unknown but immune dysfunction may be a contributing factor. Patients with autoimmune diseases were identified from the Swedish Hospital Discharge Register and linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent CUP and compared with subjects without autoimmune diseases. A total of 789,681 patients were hospitalized for any of 32 autoimmune diseases during years 1964-2012; 2658 developed subsequent CUP, giving an overall SIR of 1.27. A total of 16 autoimmune diseases were associated with an increased risk for CUP; polymyositis/dermatomyositis showed the highest SIR of 3.51, followed by primary biliary cirrhosis (1.81) and Addison's disease (1.77). CUP risk is known to be reduced in long-time users of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin. For patients with ankylosing spondylitis and with some other autoimmune diseases, with assumed chronic medication by NSAIDSs, CUP risks decreased in long-term follow-up. The overall risk of CUP was increased among patients diagnosed with autoimmune diseases, which call for clinical attention and suggest a possible role of immune dysfunction in CUP. The associations with many autoimmune diseases were weak which may imply that autoimmunity may not synergize with CUP-related immune dysfunction. However, long-term NSAID medication probably helped to curtail risks in some autoimmune diseases and CUP risks were generally higher in autoimmune diseases for which NSAIDs are not used and for these CUP appears to be a serious side-effect. This article is protected by copyright. All rights reserved.
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| 5. |
- 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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| 6. |
- Liu, Xiangdong, et al.
(författare)
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Cancer risk and mortality in asthma patients: A Swedish national cohort study.
- 2015
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Ingår i: Acta Oncologica. - 1651-226X. ; 54:8, s. 1120-1127
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Tidskriftsartikel (refereegranskat)abstract
- Background. Previous studies found an increased risk of cancer in hospitalized asthma patients, but it is not known whether patients from primary health care show a similar risk pattern. In addition, it is unclear whether the diagnosis of asthma can influence the prognosis of subsequent cancer. Methods. Asthma patients were identified from Swedish inpatient, outpatient, and primary health care registers, and were linked to the Swedish Cancer Registry to identify subsequent diagnoses of cancer. Standardized incidence ratios (SIRs) were used to examine the risk of cancer in asthma patients compared with subjects without asthma. In addition, we used Cox proportional hazards regression to estimate hazard ratios (HRs) for mortality in patients with both asthma and cancer. Results. A total of 10 649 cancers were diagnosed in patients with previous asthma, with a SIR of 1.19 (95% CI 1.17-1.21). A total of 15 cancer sites showed an increased incidence, whereas two cancer sites showed a decreased risk. Non-allergic asthma showed the highest risk of cancer (SIR = 1.25, 95% CI 1.18-1.32), followed by unspecified asthma (SIR = 1.22, 95% CI 1.19-1.25), status asthmaticus (SIR = 1.19, 95% CI 1.02-1.39), and allergic asthma (SIR = 1.14, 95% CI 1.06-1.22). The risk of cancer was similarly increased in asthma patients diagnosed in primary health care and those diagnosed in hospitals. Cancer patients with previous asthma had increased mortality, with a HR of 1.55 (95% CI 1.50-1.60). HRs ranged from 1.09 to 1.94 for different sites/types of cancer. Conclusions. Patients with asthma, irrespective of whether they were treated in primary health care or hospitals, had an increased risk of cancer. In addition, cancer patients with previous asthma had a worse prognosis compared with those without asthma, suggesting that these patients may require a multidisciplinary approach to manage the comorbidity.
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| 7. |
- Liu, Xiangdong, et al.
(författare)
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Cancer risk in patients with type 2 diabetes mellitus and their relatives.
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 137:4, s. 903-910
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies indicate that risks of certain cancers are increased in individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be representative of the entire population of T2DM patients as most of them are treated in primary health cares. To examine the subsequent cancer risk in individuals with T2DM from hospitals and primary health cares, and in their siblings and spouses, standardized incidence ratios (SIRs) were used to assess systematically risks of 35 cancer sites/types in individuals with T2DM using a nationwide Swedish database covering the period 1964 through 2010. Increased SIRs were recorded for 24 cancer sites/types in individuals with T2DM. The highest SIRs were for pancreatic cancer and liver cancer (2.98 and 2.43, respectively). A decreased SIR was noted for prostate cancer. Five cancers showed increased SIRs during the whole follow-up period: colon, liver, pancreatic, endometrial, and kidney cancers. T2DM patients in inpatient, outpatient and primary health care showed similar risk patterns. The overall SIRs for cancer in the siblings and spouses of individuals with T2DM were 0.97 and 1.01, respectively. The insulin users showed an overall increased risk of cancer. This study showed increased risks of 24 cancers in individuals with T2DM, but not in their siblings or spouses, suggesting that the profound metabolic disturbances of the underlying disease may explain the observed increases. Further studies examining the endogenous and exogenous factors underlying these associations are needed. This article is protected by copyright. All rights reserved.
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