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Sökning: WFRF:(Ji Jianguang)

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1.
  • Jin, Ying-Hui, et al. (författare)
  • Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
  • 2020
  • Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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2.
  • Ai, Jin Wei, et al. (författare)
  • Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms : An Analysis of Seven Patients in China
  • 2020
  • Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3–16 days), 7 with anorexia (7–22 days), 6 with upper abdominal discomfort (1–7 days), and 4 with nausea (1–7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.
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3.
  • Calling, Susanna, et al. (författare)
  • Shared and non-shared familial susceptibility of coronary heart disease, ischemic stroke, peripheral artery disease and aortic disease.
  • 2013
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 168:3, s. 2844-2850
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Little is known about whether the four main manifestations of arterial vascular disease (coronary heart disease=CHD, ischemic stroke, peripheral artery disease=PAD, and aortic (i.e. atherosclerosis/aneurysm) disease=AD) share familial susceptibility. The aim of this nationwide study was to determine the familial risks of concordant (same disease in proband and exposed relative) and discordant (different disease in proband and exposed relative) cardiovascular disease (CVD). METHODS: Data from the Swedish Multigeneration Register on individuals aged 0-76years were linked to Swedish Hospital Discharge Register data for the period 1964-2008. Standardized incidence ratios (SIRs) for CHD (n=140,708 cases), ischemic stroke (n=73,771), PAD (n=18,982) and AD (n=7879) were calculated for siblings of individuals hospitalized due to CHD, stroke, PAD or AD compared to those of unaffected siblings. The procedure was repeated for parent-offspring and spouses. RESULTS: All concordant and discordant sibling risks were increased for both males and females. Concordant risks were generally higher than discordant risks. The highest sibling risks were observed for premature concordant disease (<55years for males and <65years for females): SIR for CHD=1.93 (95% CI: 1.90-1.96), SIR for ischemic stroke=1.45 (1.39-1.50), SIR for PAD=2.76 (2.54-3.00), and SIR for AD=6.36 (5.28-7.59). Premature parent-offspring transmission followed the same pattern. The disease risk was modestly increased in spouses, highest for AD (SIR=1.48 (1.28-1.69)) and PAD (SIR=1.27 (1.21-1.32)). CONCLUSIONS: The four main manifestations of CVD share familial susceptibility, but unique site-specific familial factors may exist.
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4.
  • Castro, Felipe A., et al. (författare)
  • Increased Risk of Hepatobiliary Cancers After Hospitalization for Autoimmune Disease
  • 2014
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-7714 .- 1542-3565. ; 12:6, s. 1038-1045
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Some autoimmune diseases are associated with increased risk of liver cancer. However, there has been no comprehensive evaluation of autoimmune diseases among patients who develop different subtypes of hepatobiliary cancer. We examined the association between autoimmune diseases and cancers of the liver and biliary tract in the Swedish population. METHODS: We analyzed data from national datasets at the Center for Primary Health Care Research (Lund University, Sweden). Data on patients with autoimmune disorders were retrieved from the Swedish Hospital Discharge Register, from 1964 through 2008; 33 diseases were evaluated. Hepatobiliary cancer cases were retrieved from the Swedish Cancer Registry. We calculated standardized incidence ratios (SIRs) and hazard ratios for incident cancers and deaths from hepatobiliary cancers. RESULTS: Among 402,462 patients with autoimmune disorders, 582 were diagnosed with primary liver cancer, 330 with gallbladder cancer, 115 with extrahepatic bile duct cancer, and 43 with ampulla of Vater cancers. We identified 14 autoimmune conditions that were significantly associated with increased risk of primary liver cancer (overall SIR [any autoimmune disease], 2.1; 95% confidence interval [CI], 2.0-2.3), 5 conditions associated with gallbladder cancer (overall SIR, 1.3; 95% CI, 1.1-1.4), and 3 associated with extrahepatic bile duct cancer (overall SIR, 1.6; 95% CI, 1.3-1.9). The autoimmune disorders with the strongest association with primary liver cancer were primary biliary cirrhosis (SIR, 39.5; 95% CI, 28.2-53.8) and autoimmune hepatitis (SIR, 29.0; 95% CI, 9.1-68.2); ulcerative colitis was strongly associated with extrahepatic bile duct cancer (SIR, 5.6; 95% CI, 3.6-8.4). Celiac disease, Crohn's disease, systemic sclerosis, and ulcerative colitis were associated with at least 2 types of cancer. Increased hazard ratios were observed only for patients with biliary tract cancer who had been hospitalized for autoimmune conditions. CONCLUSIONS: In a study of the Swedish population, we identified an increased risk of hepatobiliary cancers among individuals diagnosed with autoimmune disease. Associations among different cancer types indicate that shared immunomodulatory mechanisms determine susceptibility to hepatobiliary cancer.
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6.
  • Chen, Tianhui, et al. (författare)
  • Effect of a Detailed Family History of Melanoma on Risk for Other Tumors: A Cohort Study Based on the Nationwide Swedish Family-Cancer Database
  • 2014
  • Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 134:4, s. 930-936
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the Swedish Family-Cancer Database, we assessed the effect of a detailed family history of melanoma on risk for other tumors (other than melanoma). Among 248,011 individuals with a family history of melanoma, 43,931 other tumors were diagnosed from 1958 to 2010. Standardized incidence ratios (SIRs) were calculated for other tumors in patients who had a family history of melanoma, as compared with those without. A detailed family history of melanoma was investigated according to an increasing number of melanomas in either 1 or >= 2 first-degree relatives (FDRs). Associations were considered significant when there were at least two independently significant SIRs or a statistically significant trend of increasing SIRs with increasing number of melanomas in relatives. The applied criteria for significant associations were convincingly met by pancreatic, breast, prostate, and squamous cell skin tumors and ependymoma, although there was significant but not overwhelming evidence for thyroid, parathyroid, lung, and unknown primary tumors, meningioma, mycosis fungoides, and myeloid leukemia. To our knowledge, no studies have previously considered a detailed family history of melanoma and the use of internal validation to assess familial associations of melanoma with other tumors. We established associations for 12 other tumors, and the associations for myeloid leukemia, parathyroid, and unknown primary tumors are, to our knowledge, previously unreported.
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8.
  • Fallah, Mahdi, et al. (författare)
  • Autoimmune diseases associated with non-Hodgkin lymphoma: A nationwide cohort study.
  • 2014
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 25:10, s. 2025-2030
  • Tidskriftsartikel (refereegranskat)abstract
    • The cumulative risk of NHL in Sweden by age 80 years has increased to 1.1 in women and 1.6% in men in 2011. Increased risk of non-Hodgkin lymphoma (NHL) associated with personal histories of some autoimmune diseases (ADs) are known. It is unclear whether there are other NHL-related ADs and whether this association holds across different sex, age and year of diagnosis, or NHL histological subtypes.
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9.
  • Fallah, M., et al. (författare)
  • Hodgkin lymphoma after autoimmune diseases by age at diagnosis and histological subtype
  • 2014
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 25:7, s. 1397-1404
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased risk of Hodgkin lymphoma (HL) associated with personal history of several autoimmune diseases (ADs), such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and immune thrombocytopenic purpura, are known. Whether there are other HL-related ADs and whether the increased risk of HL after ADs holds across sex, age, year of diagnosis, or HL histological subtype is unclear. We systematically analyzed the risk of HL in 878 161 Swedish patients diagnosed with 33 different ADs in 1964-2010. During similar to 10-year follow-up of ADs patients, 371 incident HL cases were diagnosed. Significantly increased overall standardized incidence ratio (SIR) for HL after ADs was 2.0 (95% confidence interval: 1.8-2.2); AD-specific SIRs: autoimmune hemolytic anemia 19.9 (7.2-43.6), sarcoidosis 10.3 (7.8-13.4), systemic lupus erythematosus 8.4 (5.2-12.9), immune thrombocytopenic purpura 7.0 (3.2-13.3), polyarteritis nodosa 6.6 (1.2-19.5), polymyositis/dermatomyositis 6.3 (2.0-14.9), Behcet's disease 5.6 (2.7-10.3), Sjogren's syndrome 5.0 (2.1-9.8), rheumatoid arthritis 3.2 (2.6-3.9), polymyalgia rheumatica 2.2 (1.4-3.5), and psoriasis 1.9 (1.3-2.6). Men with AD had slightly higher risk of HL (2.4, 2.0-2.7) compared with women (1.8, 1.5-2.0). Only 23% of ADs were diagnosed before age 35 years and the overall SIR for HL diagnosis before age 35 [1.4, (1.0-1.8)] was lower than that in older ages [35 a parts per thousand currency sign age < 50: 2.1 (1.6-2.7); age a parts per thousand yen 50: 2.2 (2.0-2.5)], except for sarcoidosis [age < 35: 19.3 (10.5-32.5); 35 a parts per thousand currency sign age < 50: 10.4 (5.7-17.5); age a parts per thousand yen 50: 8.4 (5.6-12.1)]. Risks of all classical HLs significantly increased after ADs: lymphocyte depletion 3.7 (1.5-7.6), lymphocyte-rich 3.7 (2.3-5.9), mixed cellularity 2.4 (1.8-3.2), and nodular sclerosis 1.7 (1.3-2.1). Several, but not all ADs (11/33), had a positive association with all classical histological subtypes of HL. Higher risks of classical HL after polyarteritis nodosa, polymyositis/dermatomyositis, Behcet's disease, Sjogren's syndrome, polymyalgia rheumatica, and psoriasis were novel findings of this study.
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10.
  • Frank, Christoph, et al. (författare)
  • The population impact of familial cancer, a major cause of cancer
  • 2014
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 134:8, s. 906-1899
  • Tidskriftsartikel (refereegranskat)abstract
    • The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many cancers, but an unbiased estimation of the PAF for familial risk requires a large study population to include rare cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were calculated for familial relative risk among first-degree relatives (FDRs) and second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or in situ cancers. Calculations were based on the Swedish Family-Cancer Database considering 8,148,737 individuals. To assess environmental effects, PAFs were also calculated for concordant cancers among spouses. Almost all cancers showed a significant familial risk. The highest PAFs were found for the common cancers of the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In the FDRs, the overall PAF for any concordant cancer was 4.20%, but in the SDRs, it was only 0.34%. The overall PAFs for in situ cancers were 0.86% and 0.56% for the FDRs and SDRs, respectively. The overall independent familial PAF was 5.96% for the invasive and in situ cancers in the FDRs and SDRs. The cancers between spouses yielded an overall PAF of 0.14%. For esophageal cancer, the risk among spouses was higher than the familial risk. Our study shows that the overall familial PAF of 5.96%, although underestimated for sex-specific cancers, ranks as the third most common population burden after tobacco smoking and unhealthy diet.
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11.
  • Freccero, Carl, et al. (författare)
  • Primary adherence to antidepressant prescriptions in primary health care: a population-based study in Sweden.
  • 2016
  • Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 34:1, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Medical adherence is important in the treatment of depression. Primary medical adherence, i.e. patients collecting their newly prescribed medications from pharmacies, is very different depending on the drug prescribed Objective To assess the rate of primary medical adherence in patients prescribed antidepressants and to identify characteristics that make patients less likely to pick up prescriptions. Methods An observational study was performed using primary health care data from Sweden on patients who were prescribed antidepressants. Univariate and multivariate logistic regression was used to determine differences in pick-up rate according to patient characteristics. Main outcome Pick-up rate, defined as collection of a prescription within 30 days. Results A total of 11 624 patients received an antidepressant prescription during the study period, and the overall pick-up rate was 85.1%. The pick-up rate differed according to country of birth: individuals born in the Middle East and other countries outside Europe had lower primary medical adherence than Swedes, with adjusted odds ratios (ORs) of 0.58 and 0.67, respectively. Patients at ages 64-79 years had a higher pick-up rate compared with those aged 25-44 years (OR 1.71). Divorced patients had a lower rate compared with married patients (OR 0.80). Conclusion Immigrants from the Middle East and other countries outside Europe and younger and divorced patients had lower primary medical adherence, which calls for clinical attention and preventive measures. Key points Primary medical adherence is important in the treatment of depression. Are patient characteristics associated with primary medical adherence? The overall primary medical adherence rate was 85%. The rate differed by country of birth, age at diagnosis of depression, and marital status. Clinical attention is needed in patients who do not pick up their antidepressants.
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12.
  • Hemminki, Kari, et al. (författare)
  • Age-Dependent Metastatic Spread and Survival : Cancer of Unknown Primary as a Model
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • 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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13.
  • Hemminki, Kari, et al. (författare)
  • Autoimmune disease and subsequent digestive tract cancer by histology
  • 2012
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:4, s. 6-927
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Dysregulation of the immune function in autoimmune diseases could potentially lead to cancer development and there is definite evidence linking some autoimmune mechanisms with cancer. We analyzed systematically the occurrence of histology-specific digestive tract cancers in patients diagnosed with 33 different autoimmune diseases in order to address the question of shared susceptibility. Patients and methods: Standardized incidence ratios (SIRs) were calculated for subsequent digestive tract cancers up to the year 2008 and in patients hospitalized for autoimmune disease after the year 1964. Results: Myasthenia gravis associated with five different cancers with SIRs ranging from 1.35 to 2.78. Pernicious anemia, Crohn disease, ulcerative colitis, systemic lupus erythematosis and psoriasis were also associated with cancers at multiple sites. Rheumatoid arthritis associated with no cancer and the standardized incidence ratio was decreased for colon adenocarcinoma, also in ankylosing spondylitis patients. Conclusions: Increased risks of cancer were observed in patients with several autoimmune diseases. Myasthenia gravis and pernicious anemia were associated with many cancers; this is possibly related to immunosuppressant medication in myasthenia gravis. The decreased risks in colon and rectal adenocarcinomas in rheumatoid arthritis and ankylosing spondylitis suggest underlying inflammatory mechanisms as the risks may have been suppressed by the use of anti-inflammatory medication.
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14.
  • Hemminki, Kari, et al. (författare)
  • Autoimmune diseases and hematological malignancies : exploring the underlying mechanisms from epidemiological evidence
  • 2020
  • Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 64, s. 114-121
  • Forskningsöversikt (refereegranskat)abstract
    • Autoimmune diseases are characterized by the irregular functioning of the immune system that leads to the loss of tolerance to self-antigens. The underlying nature of autoimmune diseases has led to speculation that the risk of malignancy might be higher or lower in patients with such diseases. However, the rarity and heterogeneity of both autoimmune diseases and malignancies is the main challenge for systematic exploration of associations between autoimmune diseases and cancer. The nationwide usages of electronic health records in Sweden and other countries has created longitudinal clinical datasets of large populations, which are ideal for quantifying the associations as well as possible guidance concerning the underlying mechanisms. In this report, we firstly summarize the population-based epidemiological association studies between autoimmune diseases and subsequent hematological malignancies using data derived mainly from Swedish nationwide data. These include over one million cancer cases and approximately 500,000 patients with medically diagnosed autoimmune disease. We further discuss the underlying mechanisms that contribute to the observed association between autoimmune diseases and hematological malignancies, including shared genetics, environmental factors, medical treatments of autoimmune diseases as well as dysregulated immune function.
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15.
  • Hemminki, Kari, et al. (författare)
  • Concordance of survival in family members with prostate cancer
  • 2008
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 26:10, s. 1705-1709
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Several earlier studies have assessed survival in prostate cancer based on familial risk of this disease. As a novel concept, we posit that factors governing survival in prostate cancer are likely to be different from those governing risk of prostate cancer. To prove this, we searched for familial clustering of survival (ie, concordance of survival among family members).PATIENTS AND METHODS: We used the nationwide Swedish Family-Cancer Database to estimate hazard rates (HRs) for cause-specific and overall survival in invasive prostate cancer. HRs show the probability of death in the study group compared with the reference group. The study covered 610 sons of affected fathers with median follow-up times for survival ranging from 34 to 76 months.RESULTS: When the survival in sons was analyzed according to the fathers' length of survival, there was a concordance of prognosis; the HR was 0.62 for sons whose fathers had survived longer than 59 months, compared with sons whose fathers had survived fewer than 24 months (P for trend, .02). On a continuous scale, the sons' survival increased almost linearly with the fathers' survival time. When the analysis was reversed and HRs were derived for fathers, the concordance of good and poor survival remained.CONCLUSION: The results are consistent in showing that both good and poor survival in prostate cancer aggregate in families. Genetic factors are likely to contribute to the results, which provide the first challenging population-level evidence on heritability in prognosis of prostate cancer.
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16.
  • Hemminki, Kari, et al. (författare)
  • Effect of autoimmune diseases on incidence and survival in subsequent multiple myeloma
  • 2012
  • Ingår i: Journal of Hematology & Oncology. - : Springer Science and Business Media LLC. - 1756-8722. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with many types of autoimmune diseases (AIDs) are at an increased risk of cancer, which may depend on underlying dysregulation of the immune system or treatment. We systematically analyzed myeloma risk and survival in patients diagnosed with 33 different AIDs. Methods: Data on patients with AIDs were retrieved from the Swedish Hospital Discharge Register and were linked to myeloma diagnoses from the Cancer Registry. Standardized incidence ratios (SIR) and hazard ratios (HRs) were calculated for subsequent myeloma between 1964 and 2008. Results: Among patients with the 33 AIDs analyzed, 457 cases of myeloma were diagnosed. The overall SIR for myeloma was 1.12 and the overall HR was 0.92 and non-significant. SIRs for myeloma were significantly increased after ankylosing spondylitis (2.02) and systemic sclerosis (2.63). Only the HR for myeloma after rheumatic fever (5.27) was significantly increased. The SIR for myeloma before age 60 years was 1.45; the SIR for myeloma was only increased in the period 1964-1990 (1.31) and not later (1.04). Only the SIR for myeloma after ankylosing spondylitis was increased in the period 1991-2008 (2.09); the HRs for myeloma were increased after polymyositis/ dermatomyositis (6.44) and rheumatic fever (4.43) but there were only three deaths of myeloma after these AIDs. Conclusions: The present data showed an increase in myeloma SIR after two AIDs, ankylosing spondylitis and systemic sclerosis, and in HR after rheumatic fever. The overall myeloma risk after any AID was no longer increased in the latter follow-up period of 1991 through 2008.
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17.
  • Hemminki, Kari, et al. (författare)
  • Effect of autoimmune diseases on mortality and survival in subsequent digestive tract cancers
  • 2012
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:8, s. 2179-2184
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with some autoimmune diseases (AIDs) are at increased risk of cancer, possibly a result of an underlying dysregulation of the immune system, medication, treatment or, probably, surveillance bias. Data on cancer mortality and survival in patients previously diagnosed with AIDs would provide novel information on these comorbidities and their clinical implications. Standardized mortality ratios (SMRs) and hazard ratios (HRs) were calculated for subsequent deaths from seven digestive tract cancers between 1964 and 2008 in patients hospitalized for any of 33 AIDs. There were 33 increased SMRs for specific cancers after a defined AID; similarly, 21 HRs were increased. Both the SMR and HR were increased after 10 autoimmune disorders, including pernicious anemia, systemic lupus erythematosus and psoriasis. Increased SMRs and unchanged HRs were noted for 23 cancers. Myasthenia gravis was associated with SMRs for five cancers but no increases in HRs. For nine cancers, including esophageal cancer after ulcerative colitis and rheumatoid arthritis, the SMR was unchanged but the HR increased. The increases in SMRs provide evidence that cancer risks were truly increased and largely unaffected by surveillance bias. The prognostic survival data should contribute to clinical evaluation and therapeutic planning.
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18.
  • Hemminki, Kari, et al. (författare)
  • Effect of autoimmune diseases on risk and survival in female cancers.
  • 2012
  • Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 127:1, s. 180-185
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Patients with autoimmune (AI) diseases are diagnosed with increased frequencies of some cancers, which may depend on the underlying dysregulation of the immune system or treatment. Data on female cancers are limited. METHODS: We analyzed systematically risk and survival of female cancers of the breast, uterus, ovary and other genital organs in close to 200,000 patients diagnosed with any of 33 different AI diseases. Standardized incidence ratios (SIRs) for risk and hazard ratios (HRs) for survival were calculated for subsequent incident cancers or cancer deaths up to year 2008. RESULTS: For all breast cancer after any AI diseases, the SIR was 0.94; SIRs were modestly increased after two AI diseases and decreased after nine AI diseases, including Sjogren syndrome (0.46). For cervical cancer, the risk was increased after discoid lupus erythematosus (3.34) and systemic sclerosis (2.43). The HR was 2.12 in chronic rheumatic heart disease patients. The overall SIR for endometrial cancer was 0.85, with low SIR in ankylosing spondylitis (0.37); the HR was 4.05 for Sjogren syndrome. The SIR for ovarian cancer was increased for polymyositis/dermatomyositis (3.26) while the HR was increased for multiple sclerosis (2.43). The overall SIR for other genital cancers was increased to 1.54 and a very high risk of 35.88 was observed in localized scleroderma. CONCLUSIONS: Breast, endometrial and ovarian cancers were decreased after all AI diseases and most significant changes after individual AI diseases were towards lower risks. Probably treatment related factors explain the findings. For cervical and other genital cancers all significant changes were increased risks.
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19.
  • Hemminki, Kari, et al. (författare)
  • Effect of autoimmune diseases on risk and survival in histology-specific lung cancer
  • 2012
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 40:6, s. 1489-1495
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with autoimmune diseases are at an increased risk of cancer due to underlying dysregulation of the immune system or treatment. Data on cancer incidence, mortality and survival after autoimmune diseases would provide further information on the clinical implications. We systematically analysed data on lung cancer in patients diagnosed with 33 different autoimmune diseases. Standardised incidence ratios (SIRs), standardised mortality ratios (SMRs) and hazard ratios (HRs) were calculated for subsequent incident lung cancers or lung cancer deaths up to 2008 in patients hospitalised for autoimmune disease after 1964. Increased risks of lung cancer were recorded for SIRs after 12 autoimmune diseases, SMRs after 11 autoimmune diseases and HRs after two autoimmune diseases. The highest SIRs and SMRs, respectively, were seen after discoid lupus erythematosus (4.71 and 4.80), polymyosistis/dermatomyositis (4.20 and 4.17), systemic lupus erythematosus (2.47 and 2.69), rheumatic fever (2.07 and 2.07) and systemic sclerosis (2.19 and 1.98). Autoimmune disease did not influence survival overall but some autoimmune diseases appeared to impair survival in small cell carcinoma. All autoimmune diseases that had an SIR >2.0 are known to present with lung manifestations, suggesting that the autoimmune process contributes to lung cancer susceptibility. The data on survival are reassuring that autoimmune diseases do not influence prognosis in lung cancer.
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20.
  • Hemminki, Kari, et al. (författare)
  • Familial bladder cancer and the related genes.
  • 2011
  • Ingår i: Current Opinion in Urology. - 0963-0643. ; 21, s. 386-392
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE OF REVIEW: Family history of bladder cancer is a known risk factor for bladder cancer but new data have emerged on the influence of a family history of other tumours than bladder cancer. Recent data have shown that family history influences survival of bladder cancer. Gene identification has been successful particularly on low-risk genes influencing susceptibility and prognosis. RECENT FINDINGS: Familial clustering of bladder cancer has been found with cancers of the stomach, larynx, kidney, endometrium and the bone marrow (leukaemia). Shared smoking habits are an explanation to these findings and between spouses these appear to be the only explanation to the clustering of cancers with bladder cancer. Family members also share prognosis of bladder cancer, either good or poor survival. Among the low-penetrant genes, the variants within the genes encoding metabolic enzymes have been consistently associated with susceptibility to bladder cancer and the evidence is compelling for NAT2 slow acetylator and GSTM1 null genotypes. SUMMARY: Smoking is the only identifiable environmental factor explaining familial clustering of bladder cancers and other cancers. Genetic factors are likely to contribute to many of the described associations but the identified genes are probably an introduction to the genetics of bladder cancer.
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21.
  • Hemminki, Kari, et al. (författare)
  • Familial risks for hospitalized Graves' disease and goiter
  • 2009
  • Ingår i: European Journal of Endocrinology. - 1479-683X. ; 161:4, s. 623-629
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Familial Clustering of a disease is an indicator of a possible heritable Cause. provided that environmental sharing can be excluded. Thus. data on familial risks are important For genetic Studies and for clinical genetic counseling. Design: We carried Out a nationwide family study on nontoxic and toxic nodular goiters, and Graves' disease in order to search for familial clustering of these diseases at the population level. Methods: The Swedish Multigeneration Register on 0-75 year old Subjects was linked to the Hospital Discharge Register from years 1987 to 2007. Standardized incidence ratios (SIRs) were calculated for offspring of affected parents and for siblings by comparing to those whose relatives had no hospitalization for thyroid disease. Results: The number of hospitalized patients in the offspring generations was 11 659 for nontoxic goiter, 9514 for Graves' disease, and 1728 For toxic nodular goiter. Familial Cases accounted for 8.2, 5.2, and 2.1% of all patients respectively The highest familial risk for offspring of affected parents was noted for Graves' disease (SIR 3.87), followed by toxic nodular goiter (3.37) and nontoxic goiter (3.15). Familial risks were higher for affected siblings: toxic nodular goiter (11.66). Graves' disease (5.51). and nontoxic goiter (5.40). Weaker familial associations were observed between the three diseases. Conclusions: To Our knowledge this is it first population-based family study On these thyroid diseases. The observed high familial aggregation for defined thyroid diseases cannot be explained by the known genetic basis, calling for further Studies into genetic and environmental etiology of thyroid diseases.
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22.
  • Hemminki, Kari, et al. (författare)
  • Familial risks in cancer of unknown primary: tracking the primary sites.
  • 2011
  • Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 29:4, s. 435-440
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE Cancer of unknown primary (CUP) is diagnosed at the metastatic stage, and despite extensive diagnostic work-up, the primary tumor often remains unidentified. No data are available on familial clustering of CUP. We hypothesize that familial clustering of CUP with other cancers may be informative of the primary sites. PATIENTS AND METHODS A total of 35,168 patients with CUP were identified in the Swedish Family-Cancer Database, and risks between family members were calculated for concordant (CUP-CUP) and discordant (CUP-any other cancer) cancers using standardized incidence ratio (SIR). Results Familial cases of CUP accounted for 2.8% of all CUP cases in the offspring generation. Familial SIR for CUP was 1.69 when a sibling was diagnosed with CUP. As to discordant associations between siblings, CUP was associated with lung (SIR, 1.87), kidney (SIR, 1.82), liver (SIR, 1.67), ovarian (SIR, 1.45), colorectal (SIR, 1.26), and breast (SIR, 1.15) cancers and melanoma (SIR, 1.26). Upper aerodigestive tract, bladder, pancreatic, and prostate cancers were additionally associated with CUP. Notably, CUP was associated with families of kidney, lung, and colorectal cancers. CONCLUSION The present data show that CUP is not a disease of random metastatic cancers but, instead, a disease of a defined set of cancers. The association of CUP with families of kidney, lung, and colorectal cancers suggests a marked genetic basis and shared metastatic mechanisms by many cancer types. Familial sites shared by CUP generally match those arising in tissue-of-origin determinations and, hence, suggest sites of origin for CUP. Mechanistic exploration of CUP may provide insight into defense against primary tumors and the metastatic process.
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23.
  • Hemminki, Kari, et al. (författare)
  • Histology-specific risks in testicular cancer in immigrants to Sweden
  • 2010
  • Ingår i: Endocrine-Related Cancer. - 1479-6821. ; 17:2, s. 329-334
  • Tidskriftsartikel (refereegranskat)abstract
    • The changes of cancer incidence upon immigration have been used as an estimator of environmental influence on cancer risk. The previous immigrant studies have indicated that the origins of testicular cancer are at an early age in life, probably in the intrauterine period. We wanted to reexamine the critical periods on histology-specific testicular cancer in sons of immigrants to Sweden. We used the nationwide Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for testicular cancer in sons of parents immigrating to Sweden from low-and high-risk countries compared with the native Swedes. Among the large immigrant groups, the SIRs for sons of two Finnish and Asian parents were decreased if the sons were born outside Sweden. The sons of a Danish immigrant couple showed an increased risk of testicular cancer. The changes in SIR were most systematic for seminoma. The present patterns of testicular cancer risk among sons of immigrants point to the early environmental risk factors, which influence the risk probably after the intrauterine period. These factors appear to influence seminoma risk in a more enduring way than they influence non-seminoma. Endocrine-Related Cancer (2010) 17 329-334
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24.
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25.
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26.
  • Hemminki, Kari, et al. (författare)
  • Liver and gallbladder cancer in immigrants to Sweden.
  • 2010
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 46, s. 926-931
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The changes of cancer incidence upon immigration can be used as an estimator of environmental influence on cancer risk. We studied site-specific liver and biliary cancers in first-generation immigrants to Sweden with an aim to search for aetiological clues and to find evidence for indigenous incidence rates. MATERIAL AND METHODS: We used the nation-wide Swedish Family-Cancer Database to calculate standardised incidence ratios (SIRs) in immigrants compared to native Swedes. RESULTS: A total of 1428 cancers were identified in immigrants whose median ages (years) at immigration were 27 for men and 26 for women and whose median diagnostic ages were 64 and 66, respectively. The highest SIRs of 6.7 for primary liver cancer were observed for men from East Asia and sub-Saharan Africa. Increased SIRs were recorded for male immigrants from previous Yugoslavia (1.78), Southern Europe (2.91), Turkey (2.15) and Asian Arab countries (2.89). For gallbladder cancer, only women from the Indian subcontinent (3.84) and Chile (2.34) had increased risk while some Northern European immigrants showed decreased risks. CONCLUSIONS: Primary liver cancer was increased in immigrants from endemic regions of hepatitis B virus infection but also from large regions lacking cancer incidence data, North Africa, Asian Arab countries, Turkey and previous Yugoslavia; these are probably intermediary risk regions for this infection. The consideration of these regions as risk areas would justify active diagnostic and vaccination programs. The increase in gallbladder cancer in Chileans and Indians suggests that some persistent damage was inflicted before emigration, characterisation of which will be a challenge for aetiological studies.
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27.
  • Hemminki, Kari, et al. (författare)
  • Location of metastases in cancer of unknown primary are not random and signal familial clustering.
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • 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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28.
  • Hemminki, Kari, et al. (författare)
  • Origin of B-cell neoplasms in autoimmune disease
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
  • 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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29.
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30.
  • Hemminki, Kari, et al. (författare)
  • Risk of cancer in patients with medically diagnosed hay fever or allergic rhinitis.
  • 2014
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 135:10, s. 2397-2403
  • Tidskriftsartikel (refereegranskat)abstract
    • Data on allergic conditions as risk or protective factors for cancer are controversial probably because most studies have used self-reported data on mixed groups of allergies in a case-control setting. We define cancer risks in medically diagnosed hay fever/allergic rhinitis patients in a nationwide cohort study. A total of 138,723 hay fever/allergic rhinitis patients were identified from three Swedish health care databases and standardized incidence ratios (SIRs) were calculated for subsequent cancers identified from the Swedish Cancer Registry. Overall cancer risk was not changed (SIR 1.03). For individual cancers, the highest SIR was observed for nasal cancer (SIR 2.63), followed by testicular (1.46) and endocrine tumors (1.42), and kidney (1.31), prostate (1.18) and breast (1.11) cancers. The results were consistent in the three sources of data and all SIRs were above unity, albeit mainly not statistically significant. The SIRs for nervous system tumors were above unity and of borderline significance. SIRs were decreased for esophageal (0.50), liver (0.62) and lung (0.78) cancers, and the three sources of data agreed in the direction of the effect. The increased risks for testicular, renal, prostate and endocrine cancers may be explained by immunological mechanisms. Excess risk for these cancer accounts for a significant population attributable fraction. Nervous system cancers showed a borderline increase and none of the histological types were significantly decreased, providing strong evidence against the published case-control studies, which have reported protective effects. The reasons for the reduced risks for esophageal, liver and lung cancer remain to be explained.
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31.
  • Hemminki, Kari, et al. (författare)
  • Risk of Cancer of Unknown Primary after Hospitalization for Autoimmune Diseases.
  • 2015
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 137:12, s. 2885-2895
  • 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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32.
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33.
  • Hemminki, Kari, et al. (författare)
  • Subsequent brain tumors in patients with autoimmune disease.
  • 2013
  • Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 15:9, s. 1142-1150
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPrevious studies have reported increased risk of brain tumors after allergic conditions, but no systematic analyses of these tumors in patients with autoimmune disease (AId) have been performed. No data are available on survival among patients with AId from brain tumors. We analyzed systematically risks and survival in histological types of brain tumors among patients who received a diagnosis of 33 different AIds.Patients and MethodsStandardized incidence ratios (SIRs) for brain tumors or hazard ratios (HRs) of deaths after brain tumors were calculated up to 2008 in 402 462 patients hospitalized for AId after 1964 and were compared with data on the population not hospitalized for AIds.ResultsBrain tumors were diagnosed in 880 patients with AId. No increased or decreased risks (SIRs) were noted for glioma, whereas the increased SIRs for meningioma after many AIds were likely to be attributable to surveillance bias. The data on survival showed overall decreases for glioma (HR, 1.15) and meningioma (HR, 1.26). The survival in both was decreased in patients with chronic rheumatic heart disease, multiple sclerosis, and rheumatoid arthritis. Overall, HRs were increased for glioma after 6 AIds and for meningioma after 7 AIds.ConclusionsThe present data showed that none of the 33 AIds influenced the risk of glioma. However, many AIds negatively influence survival in glioma and meningioma, probably through added physical burden or therapeutic limitations. Information of an existing AId in patients with newly diagnosed brain tumors should help the prognostic assessment and the design of treatment.
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34.
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35.
  • Hemminki, Kari, et al. (författare)
  • Subsequent leukaemia in autoimmune disease patients.
  • 2013
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 161:5, s. 677-687
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have shown that patients diagnosed with some autoimmune (AI) diseases are at an increased risk of leukaemia but limited data are available on survival. We systematically analysed the risks (standardized incidence ratio, SIR) and survival (hazard ratio, HR) in nine types of leukaemia among 402 462 patients hospitalized for any of 33 AI diseases and compared to persons not hospitalized for AI diseases. Risk for all leukaemia was increased after 13 AI diseases and survival was decreased after six AI diseases. SIRs were increased after all AI diseases for seven types of leukaemia, including SIR 1·69 (95% confidence interval (CI): 1·29-2·19) for acute lymphoblastic leukaemia (ALL), 1·85 (95% CI: 1·65-2·07) for acute myeloid leukaemia, 1·68 (95% CI: 1·37-2·04) for chronic myeloid leukaemia, 2·20 (95% CI: 1·69-2·81) for 'other myeloid leukaemia', 2·45 (95% 1·99-2·98) for 'other and unspecified leukaemia', 1·81 (95% CI: 1·11-2·81) for monocytic leukaemia, and 1·36 (95% CI: 1·08-1·69) for myelofibrosis. The HRs were increased for four types of leukaemia, most for myelofibrosis (1·74, 95% CI: 1·33-2·29) and ALL (1·42, 95% CI: 1·03-1·95). Some AI diseases, including rheumatoid arthritis, were associated with increased SIRs and HRs in many types of leukaemia. The present data showed increases in risk and decreases in survival for many types of leukaemia after various AI diseases. Leukaemia is a rare complication in AI disease but findings about this comorbidity at the time of leukaemia diagnosis may help to optimize the treatment and improve survival.
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36.
  • Hemminki, Kari, et al. (författare)
  • Subsequent Type 2 Diabetes in Patients with Autoimmune Disease.
  • 2015
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
  • 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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37.
  • Hemminki, Kari, et al. (författare)
  • Survival in breast cancer is familial
  • 2008
  • Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 110:1, s. 177-182
  • Tidskriftsartikel (refereegranskat)abstract
    • Several earlier studies have assessed survival in breast cancer based on familial risk of this disease. The results have been conflicting and suggest that the risk and prognostic factors of cancer are largely distinct. As a novel concept, we searched for familial clustering of survival, i.e., concordance of survival among family members. We used the nation-wide Swedish Family-Cancer Database to estimate hazard ratios (HRs) for cause-specific and overall survival in invasive breast cancer. HR shows the probability of death in the study group compared the reference group. The study covered 1277 mother-daughter pairs with familial breast cancer. Their median follow-up times for survival ranged from 96 to 122 months. When the survival in daughters was analyzed according to the mothers' length of survival, there was a concordance of prognosis. The HR was 0.65 in daughters whose mothers had survived > or = 120 months compared to daughters whose mothers had survived less than 36 months (P-value for trend 0.02). When the analysis was reversed and HRs were derived for mothers, the results were essentially similar (P-value for trend 0.02). The survival did not differ between patients with familial or sporadic breast cancer. The results are consistent in showing that both good and poor survival in breast cancer aggregates in families, which is a novel population-level finding for any cancer. The consistency of the results suggests that the prognosis in breast cancer is in part heritable which is likely to be explained by yet unknown genetic mechanisms.
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38.
  • Hemminki, Karl, et al. (författare)
  • The Swedish Family-Cancer Database 2009: prospects for histology-specific and immigrant studies
  • 2010
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:10, s. 2259-2267
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish Family-Cancer Database comprises a total of 11.8 million individuals covering the Swedish population of the past 100 years. Version VIII of the Database is described in the present article. Cancer cases were retrieved from the Swedish Cancer Registry for the period 1958-2006, including more than 1 million first primary cancers. The number of familial cancers in offspring is 14,000 when a parent was diagnosed with a concordant (same) cancer and the number of concordant siblings was 6,000. From the year 1993 onwards histopathological data according to the SNOMED classification were used, which entails advantages for certain cancers, such as breast cancer. Even though the specific morphological classification only covers a limited number of years, it does cover most familial cancers in the offspring generation. The Database records the country of birth for each subject. A total of 1.79 million individuals were foreign born, Finns and other Scandinavians being the largest immigrant groups. The cancer incidence in the first-generation immigrants was compared to that in native Swedes using standardised incidence ratios (SIRs) to measure relative risk. The SIRs ranged widely between the immigrant groups, from 1.9-fold for myeloma to 25-fold for melanoma. The differences in SIRs were smaller in the second-generation immigrants. The usefulness and the possible applications of the Family-Cancer Database have increased with increasing numbers of cases, and the numerous applications have been described in some 300 publications. Familial cancer studies are in the stimulating interphase of the flourishing disciplines of genetics and epidemiology.
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39.
  • Hosseinali Khani, Maziar, 1975-, et al. (författare)
  • Socioeconomic characteristics and comorbidities of diverticular disease in Sweden 1997-2012
  • 2017
  • Ingår i: International Journal of Colorectal Disease. - : SPRINGER. - 0179-1958 .- 1432-1262. ; 32:11, s. 1591-1596
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: This study aimed to evaluate the association of socioeconomic status and comorbidities with uncomplicated and complicated diverticular disease (DD) in Sweden.Methods: We identified all individuals aged >= 30 years in Sweden diagnosed with DD between 1997 and 2012 using the Swedish National Population and Housing Census and the Hospital Discharge Register. Data were analyzed by multivariable logistic regression, with individual-level characteristics as covariates.Results: A total of 79,481 patients (median age 66 [range 3086] years) were hospitalized for DD, 15,878 (20%) of whom for complicated DD. Admissions for both uncomplicated and complicated DD were more common in women (p < 0.001). A low education level was identified as a risk factor for uncomplicated (unadjusted hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.75-1.82; adjusted HR 1.22, 95% CI 1.19-1.24) and complicated DD(unadjusted HR 1.84, 95% CI 1.77-1.92; adjusted HR 1.26, 95% CI 1.21-1.32). Patients with the lowest income had a lower risk of hospitalization for uncomplicated (adjusted HR 0.94, 95% CI 0.91-0.96) and complicated DD (adjusted HR 0.87, 95% CI 0.83-0.92) than those with the highest income. The correlation coefficient between income and education was 0.25. Diabetes and cardiovascular disease were identified as protective factors against uncomplicated DD (adjusted HR 0.68, 95% CI 0.66-0.69 and HR 0.79, 95% CI 0.74-0.84, respectively).Conclusions: Patients with the lowest education level had an increased risk of hospitalization for DD. Further studies are needed to explore the association of diabetes and cardiovascular disease with uncomplicated DD.
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40.
  • Hu, Li-Peng, et al. (författare)
  • Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression
  • 2022
  • Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0024 .- 1525-0016. ; 30:10, s. 3284-3299
  • Tidskriftsartikel (refereegranskat)abstract
    • Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio=0.50) and metastasis (hazard ratio=0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP+) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation and cell cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.
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41.
  • Huang, Qiulin, et al. (författare)
  • Burden of malignant mesothelioma in China during 1990-2019 and the projections through 2029
  • Ingår i: Journal of the National Cancer Center. - 2667-0054.
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo provide the most up-to-date data on the burden of malignant mesothelioma (MM) and the projections through 2029 in China.MethodsData on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease (GBD) 2019 database, including annual cases and deaths data and age-standardized rates of incidence, mortality, and disability-adjusted life-years (DALYs) associated with MM among different age groups. Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95% confidence interval (CI), while the projections through 2029 were calculated by Bayesian age-period-cohort model. Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.ResultsWe observed a significant elevation in incident new cases and deaths over last 3 decades, increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases. We found roughly 6% increase in the proportion of incident cases for those aged > 70 years (30% in 2019 versus 24% in 1990), while for the proportion of deaths similar elevation for those aged > 70 years was also found. Additionally, men had significantly higher DALYs due to MM across age groups compared to women. Asbestos consumption in China dramatically dropped since 2012 and reached bottom in 2017 with 230 kilotons. By 2029, the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.ConclusionWe found, for the first time using GBD data on the Chinese population, that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade, suggesting an urgent need for a complete ban on chrysotile asbestos in China.
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42.
  • Huang, Shan, et al. (författare)
  • Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner
  • 2023
  • Ingår i: Cellular Oncology. - : Springer Science and Business Media LLC. - 2211-3428 .- 2211-3436. ; 46:4, s. 953-967
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Available evidence indicates that dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes. Aspirin is a well-known non-steroid anti-inflammatory drug. This anti-inflammatory property has turned aspirin into a potential drug for inflammation-related cancers such as colorectal cancer (CRC). Here, we aimed to explore whether the anti-cancer effect of aspirin against CRC could be improved by combined administration with dipyridamole.METHODS: Population-based clinical data analysis was conducted to assess a possible therapeutic effect of combined dipyridamole and aspirin treatment in inhibiting CRC compared with either monotherapy. This therapeutic effect was further verified in different CRC mouse models, i.e. an orthotopic xenograft mouse model, an AOM/DSS mouse model, an Apc min/+ mouse model and a patient derived xenograft (PDX) mouse model. The in vitro effects of the drugs on CRC cells were tested using CCK8 and flow cytometry assays. RNA-Seq, Western blotting, qRT-PCR and flow cytometry were used to identify the underlying molecular mechanisms. RESULTS: We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect.CONCLUSIONS: Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents.
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43.
  • Huang, Wuqing, et al. (författare)
  • Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study
  • 2021
  • Ingår i: eLife. - 2050-084X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lipid metabolism plays an important role in viral infections. We aimed to assess the causal effect of lipid-lowering drugs (HMGCR inhibitiors, PCSK9 inhibitiors and NPC1L1 inhibitior) on COVID-19 outcomes using 2-sample Mendelian Randomization (MR) study.Methods: We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including eQTLs of drugs target genes, and genetic variants within or nearby drugs target genes associated with LDL cholesterol from GWAS. Summary-data-based MR (SMR) and inverse-variance weighted MR (IVW-MR) were used to calculate the effect estimates.Results: SMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (OR=1.38, 95%CI=1.06-1.81). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR=1.32, 95%CI=1.00-1.74). No consistent evidence from both analyses was found for other associations.Conclusions: This 2-sample MR study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization.Funding: Fujian Province Major Science and Technology Program.
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44.
  • Huang, Wuqing, et al. (författare)
  • Mortality patterns in long-term survivors of childhood or adolescent central nervous system tumour in Sweden
  • 2019
  • Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 145:3, s. 541-549
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: A growing number of young patients with central nervous system (CNS) tumour survived for more than five years. However, these long-term survivors might be at risk of multiple late effects thus leading to a higher risk of late mortality. We aimed to explore the risk of late mortality and the pattern of mortality among long-term survivors of childhood or adolescent CNS tumour.METHODS: We identified 5-year survivors with childhood or adolescent CNS tumour before age 20 years through the Swedish Cancer Registry. Five controls were randomly matched for each patient to generate the reference group. We retrieved information about death via Cause of Death Register. We calculated the absolute excess risk (AER) of death and the hazard ratio (HR) of death using Cox proportional hazard model.RESULTS: Long-term survivors with CNS tumour suffered a significant higher risk of overall mortality (HR 6.56, 95% CI 5.71-7.53; AER 5.89, 95% CI 5.03-6.87). The mortality rate declined with the increasing survival time, but it was still higher even after 30 years of follow-up. Malignant neoplasms contributed mostly to late mortality with an AER of 3.75 (95% CI 2.95-4.75). Female survivors, survivors diagnosed at a younger age and survivors with medulloblastoma were particularly strongly associated with a higher risk of death.CONCLUSIONS: Long-term survivors of childhood and adolescent CNS tumours are at a higher risk of late mortality, and the risk of death is affected by gender, age at diagnosis and types of CNS tumour.
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45.
  • Huang, Wuqing, et al. (författare)
  • PDE5 inhibition mitigates heart failure in hyperlipidemia
  • 2024
  • Ingår i: Biomedicine and Pharmacotherapy. - 0753-3322. ; 175
  • Tidskriftsartikel (refereegranskat)abstract
    • PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a significantly lower risk of HF compared with patients who used alprostadil, especially among individuals with hyperlipidemia (adjusted HR = 0.56, 95% CI = 0.40–0.78). In animal models, sildenafil significantly recovered the cardiac structure and function induced by AAB surgery, as well as reversed liver dysfunction and ameliorated hyperlipidemia induced by HFD via reducing the level of ALT, AST and serum lipids. Lipidomic analysis identified four lipid metabolites involved in sildenafil administration, including FA 16:3, LPC O-18:1, DG24:0_18:0 and SE28:1/20:4. This study revealed the protective effect of PDE5 inhibitors against HF in hyperlipidemia, indicating the potential of being repurposed as an adjuvant for HF prevention in patients with hyperlipidemia if these findings can be further confirmed in clinical trials.
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46.
  • Huang, Wuqing, et al. (författare)
  • Phosphodiesterase-5 inhibitors use and risk for mortality and metastases among male patients with colorectal cancer
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3191-3191
  • Tidskriftsartikel (refereegranskat)abstract
    • Phosphodiesterase-5 (PDE5) inhibitors are suggested to have anti-tumor effects and to inhibit surgery-induced immunosuppression. We aimed to explore whether post-diagnostic use of PDE5 inhibitors was associated with a better prognosis among male patients with colorectal cancer (CRC) and the role of open surgery in the association. Here we show that post-diagnostic use of PDE5 inhibitors is associated with a decreased risk of CRC-specific mortality (adjusted HR = 0.82, 95% CI 0.67-0.99) as well as a decreased risk of metastasis (adjusted HR = 0.85, 95% CI 0.74-0.98). Specifically, post-operative use of PDE5 inhibitors has a strong anti-cancer effect. The reduced risk of metastasis is mainly due to distant metastasis but not regional lymphatic metastasis. PDE5 inhibitors have the potential to be an adjuvant drug for patients with CRC to improve prognosis, especially those who have undergone open surgery.
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47.
  • Huang, Wuqing, et al. (författare)
  • Poor academic performance in offspring of survivors with childhood or adolescent central nervous system tumor in Sweden
  • 2020
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:10, s. 2687-2694
  • Tidskriftsartikel (refereegranskat)abstract
    • The number of children who were born after their parents were diagnosed with central nervous system (CNS) tumor is increasing, but it remains largely unknown regarding the academic performance of these children. We aimed to investigate whether children of survivors with childhood or adolescent CNS tumor were associated with poor academic performance. Children of survivors of CNS tumor were identified by combining the nationwide Swedish Cancer Register and the Multi-Generation Register, and those who have completed compulsory education in Sweden between 1989 and 2015 were included in our study. “Poor academic performance” was defined as a z-score of the academic performance below the 10th percentile. Conditional logistic regression and quantile regression were used to examine the association. A total of 655 children were born after their parental diagnosis of CNS tumor and they had 1.39 times higher risk of achieving poor academic performance as compared to the matched comparisons (95% CI = 1.10-1.76). The poor academic performance was even more pronounced in boys, among those with a paternal diagnosis of CNS tumor and those with a parental ependymoma. The observed association differed depending on preterm birth. In addition, the strength of the association declined with the increased quantiles of academic performance z-score. Our data suggest that parental CNS tumor affects the subsequent academic achievements among children born after the parental tumor.
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48.
  • Huang, Wuqing, et al. (författare)
  • Psychiatric disorders in offspring of childhood or adolescent central nervous system tumor survivors : a national cohort study
  • 2021
  • Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 10:2, s. 675-683
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Children experience a higher risk of psychiatric problems when their parents are diagnosed with cancer. However, the psychological effect among offspring who are born after parental cancer diagnosed in childhood or adolescence is unknown. We aimed to investigate the risk of psychiatric disorders in children of survivors with childhood or adolescent central nervous system (CNS) tumors.METHODS: By combining several nationwide Swedish registers, we identified all children who had at least one parent previously diagnosed with CNS tumor below the age of 20. Five children without parental CNS tumor were randomly selected for the matching. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence interval (CI).RESULTS: The incidence rate of psychiatric disorders was 8.46 per 1000 person-years in children of CNS tumor survivors, whereas the rate was 7.47 in the matched comparisons, yielding an adjusted HR of 1.10 (95% CI = 0.94, 1.28). Boys of survivors had a higher risk of psychiatric disorders (adjusted HR = 1.29, 95% CI = 1.04, 1.59). The risk of the specific types of psychiatric disorders in children of tumor survivors was comparable with that in the matched comparisons, except for mental retardation. Children of survivors experienced 2.36 times higher risk of mental retardation (95% CI = 1.21, 4.58), mainly of mild mental retardation (adjusted HR = 2.99, 95% CI = 1.40, 6.38).CONCLUSION: Children of survivors with CNS tumor in early life did not experience a significantly increased risk of overall psychiatric disorders, with the exception of an elevated risk of mental retardation that was mainly mild.
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49.
  • Huang, Wuqing, et al. (författare)
  • Risk of Being Born Preterm in Offspring of Cancer Survivors : A National Cohort Study
  • 2020
  • Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: With the increased number of cancer survivors, it is necessary to explore the effect of cancer and its treatments on pregnancy outcomes, such as preterm birth, which seriously endangers the health of offspring. We aimed to explore the risk of being born preterm among offspring of cancer survivors. Materials and Methods: This is a retrospective cohort study. All singleton live births between 1973 and 2014 in Sweden with information of birth outcomes were retrieved from the Swedish Medical Birth Register. By linking to several Swedish registers, we identified all parents of children and parental cancer diagnosis. Logistic regression was used to estimate odds ratios and 95% confidence intervals. Results: As compared to the children without parental cancer, the risk of being born preterm was significantly higher among children of overall female cancer survivors born after cancer diagnosis with an adjusted OR of 1.48 (95 CI% = 1.39-1.59), in particular those diagnosed with childhood cancer and cancer in female genital organs. Besides, the risk might continuously decline with time at the first 8 years after maternal diagnosis. A higher risk of being born preterm was found among offspring of male survivors diagnosed with central nervous system cancer (Adjusted OR = 1.26, 95% CI = 1.04-1.53). Conclusions: Our study provides evidence for a higher risk of being born preterm among children of female cancer survivors and male survivors with central nervous system tumor, as well as indicates that the effect on female reproductive system from cancer and related-treatments might decline with time.
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50.
  • Huang, Wuqing, et al. (författare)
  • Risk of being born preterm in offspring of survivors with childhood or adolescent central nervous system tumour in Sweden
  • 2020
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:1, s. 100-106
  • Tidskriftsartikel (refereegranskat)abstract
    • An increasing number of patients with central nervous system (CNS) tumour could survive to reproductive age. However, it is largely unknown whether the history of CNS tumour might affect pregnancy outcome. We aimed to explore the risk of being born pretem among children of CNS tumour survivors. By linking several nationwide registers in Sweden, we identified 1369 children whose parents were childhood or adolescent CNS tumour survivors. Children whose parents did not have CNS tumour were matched randomly with a 5:1 ratio to generate the reference group. Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI). The prevalence of preterm birth (PTB) was 6.9% among children of survivors with CNS tumour and 5.2% among the matched controls. Children of survivors had an increased risk of PTB (adjusted OR=1.29, 95%CI 1.01-1.65) compared to the matched controls. This risk was increased specifically among offspring of those diagnosed in childhood (adjusted OR=1.53, 95%CI 1.14-2.06) but not adolescence (adjusted OR=0.89, 95%CI 0.56-1.41). For families with more than one child, the risk was slightly lower among the second child as compared to the first child. The risk was negatively associated with time interval between parental diagnosis and childbirth. Parental medulloblastoma and ependymoma were most strongly associated with a higher risk of PTB. Children of survivors with CNS tumour experienced an elevated risk of PTB. However, the risk diminishes gradually following parental diagnosis of CNS tumour. Offspring of childhood CNS tumour survivors and medulloblastoma or ependymoma survivors may have the highest risk of PTB. This article is protected by copyright. All rights reserved.
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