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- Wernroth, M. -L, et al.
(författare)
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Childhood bereavement and risk of type 1 diabetes : a Swedish population-based register study
- 2021
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:Suppl. 1, s. 140-140
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Loss of a first-degree family member in childhood constitutes a major psychological stressor, and is associated both with subsequent psychiatric and somatic morbidity. The potential influence on type 1 diabetes risk has however not yet been fully elucidated. In this study we therefore aimed to investigate the impact of childhood bereavement on type 1 diabetes risk.Materials and methods: We conducted a population-based study in Sweden, encompassing 2,321,318 children born in Sweden January 1 1990 to December 31 2012. The follow up ended December 31 2013, at death of the child, type 1 diabetes diagnosis, emigration or when the child turned 19 years. All children were followed from the age of one, with exposure defined as death of a mother, father, or sibling. Type 1 diabetes diagnoses were extracted from the National Patient Register. We applied Cox proportional hazards models with attained age as time scale and loss of family member as a time varying variable, adjusting for potential confounders including parental type 1 diabetes, parental country of birth, and region of residence. We further categorized child age at bereavement as pre-school (1-6 years), school age (7-12 years) and teenage (13-18 years).Results: During follow-up (median 10.8 years), 50,253 (2.2%) children experienced loss of a family member. Median age at loss was 9.6 years, and 32% of all deaths were categorized as traumatic (accident, suicide, violence, or other sudden unnatural deaths). In total 10,965 children were diagnosed with type 1 diabetes during follow-up and median age at diagnosis was 8.5 years. We observed no overall association between childhood bereavement and type 1 diabetes risk (crude HR 1.00, 95% CI 0.86-1.18, adjusted HR 0.96, 95% CI 0.82 -1.13). The risk was not influenced by sex of the child, cause of death of family member, or familial relationship to the deceased. However, we noted an association when the exposure occurred during the teenage years (adjusted HR 1.67, 95% CI 1.15-2.43).Conclusion: Overall, childhood bereavement was not associated with the risk of type 1 diabetes, but the impact of childhood loss on type 1 diabetes may be modified by age at bereavement.
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- Wernroth, Mona-Lisa
(författare)
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Type l diabetes in childhood and adolescence, environmental exposures and gut microbiota
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Environmental factors leading to disturbances in the gut microbiota might play an important role as triggers for, and/or contributing factors in, the development of type 1 diabetes (T1D). The overall aim of the research underlying this thesis was to study the influence of environmental factor exposure on the risk of T1D in childhood and adolescence, and gut microbiota composition in early childhood.In this project, national registers provided information about T1D onset and exposure to animals, antibiotics, caesarean section and severe stress, defined as death of a first degree relative. In the first study (1,999 T1D events), no evidence supported an association between early exposure to dog or farm animals and T1D in childhood. In the second study (1,297 T1D events), dispensed prescriptions of antibiotics in the first year of life was found to be associated with T1D during childhood. Sibling analysis did not indicate confounding from familial factors. Furthermore, the effect estimate for the association between antibiotics and T1D was largest in children delivered by caesarean section. In the third study (10,789 T1D events), death of a close relative was associated with an increased risk for T1D within the first years following the loss, and when the loss occurred during the teenage years. The fourth study was a longitudinal study using 16S rRNA sequencing to analyse faecal samples from 83 children to study the gut microbiota development from birth to 2 years of age. Having a furry pet in the household was associated with a lower abundance of a bacterial species belonging to the genus Bifidobacterium. The overall gut microbiota composition was associated with prenatal exposure to antibiotics and caesarean section. Finally, caesarean section was associated with a lower abundance of Bacteroidetes and a higher abundance of Firmicutes.In conclusion, no evidence was found in the present study to support the association of exposure to animals to lowered risk of T1D in the general population. Although exposure to antibiotics was associated with T1D, it is likely to only make a small contribution to the overall risk of T1D. Our findings support the hypothesis that severe stress might accelerate T1D onset during certain time periods. Furthermore, our findings add to the body of research showing that exposure to animals, prenatal antibiotics and caesarean section account for some of the inter-individual variation in early childhood microbiota development.
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- Bergh, Cecilia, 1972-
(författare)
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Life-course influences on occurrence and outcome for stroke and coronary heart disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although typical clinical onset does not occur until adulthood, cardiovascular disease (CVD) may have a long natural history with accumulation of risks beginning in early life and continuing through childhood and into adolescence and adulthood. Therefore, it is important to adopt a life-course approach to explore accumulation of risks, as well as identifying age-defined windows of susceptibility, from early life to disease onset. This thesis examines characteristics in adolescence and adulthood linked with subsequent risk of CVD. One area is concerned with physical and psychological characteristics in adolescence, which reflects inherited and acquired elements from childhood, and their association with occurrence and outcome of subsequent stroke and coronary heart disease many years later. The second area focuses on severe infections and subsequent delayed risk of CVD. Data from several Swedish registers were used to provide information on a general population-based cohort of men. Some 284 198 males, born in Sweden from 1952 to 1956 and included in the Swedish Military Conscription Register, form the basis of the study cohort for this thesis. Our results indicate that characteristics already present in adolescence may have an important role in determining long-term cardiovascular health. Stress resilience in adolescence was associated with an increased risk of stroke and CHD, working in part through other CVD factors, in particular physical fitness. Stress resilience, unhealthy BMI and elevated blood pressure in adolescence were also associated with aspects of stroke severity among survivors of a first stroke. We demonstrated an association for severe infections (hospital admission for sepsis and pneumonia) in adulthood with subsequent delayed risk of CVD, independent of risk factors from adolescence. Persistent systemic inflammatory activity which could follow infection, and that might persist long after infections resolve, represents a possible mechanism. Interventions to protect against CVD should begin by adolescence; and there may be a period of heightened susceptibility in the years following severe infection when additional monitoring and interventions for CVD may be of value.
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- Fall, Katja
(författare)
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Medical interventions and gastric cancer risk : an observational approach
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Helicobacter pylori infection is undoubtedly the most important risk factor for gastric cancer. A causal relationship with gastric cancer, however, has not been clearly established and the carcinogenic mechanism is still ambiguous. There is a growing consensus for introduction of large-scale eradication programs, but it is yet unknown if elimination of H. pylori would reduce the incidence of gastric cancer. To address this question, randomized intervention trials using gastric cancer as end-point have been initiated, but conclusive results will not be available in the near future since these trials require very large samples and lengthy follow-up. Using observational data on medical interventions, the aim of this thesis was to investigate characteristics of the relationship between H. pylori infection and gastric cancer, and to assess the risk of gastric cancer following antibiotic and anti-inflammatory treatments. In a previous cohort study of 39,000 hip replacement patients, identified in the Swedish Inpatient Register, a declining risk of gastric cancer was observed with increasing time after hip surgery. Here, we tested the hypothesis that the risk reduction was mediated through incidental eradication of H. pylori, caused by the prophylactic antibiotic treatment given at time of surgery. In a case-control study, 'nested' within the original cohort (174 cases, 462 controls), we found that both long-term antibiotic treatment before surgery (OR, 0.3 95% Cl, 0. 1-0.7) and prophylactic antibiotic treatment (OR, 0.7 95% Cl, 0.5- 1. 1) conferred a reduction in gastric cancer risk. To further test the hypothesis that exposure to heavy antibiotic treatment reduces the risk of gastric cancer, we assessed cancer risk among 336,017 patients hospitalized for one of ten selected infectious diseases, identified in the Swedish Inpatient Register. The gastric cancer risk in the infectious disease cohort was similar to that expected in the background population, and the data did thus not further support our hypothesis. As an alternative explanation, the apparent reduction in gastric cancer risk may have resulted from intense exposure to aspirin and other non-steroid anti-inflammatory drugs used by the hip replacement patients, who typically have intractable pain prior to their operations. Analysis of data from a population-based case-control study (567 cases, 1165 controls) showed a 30% (OR, 0.7 95% Cl, 0.6-1.0) reduced gastric cancer risk among users of aspirin compared to non-users, as well as an inverse trend with increased number of tablets used (p=0.02). Although largely unclear, the carcinogenic action of H. pylori is believed to be mediated through induction and maintenance of chronic inflammation. We aimed to test whether a noninfectious chronic inflammation, i.e. reactive gastritis induced by duodeno-gastric bile reflux following cholecystectomy, also increases the risk of gastric cancer. To address this issue, we assessed the gastric cancer risk within a cohort of 251,672 cholecystecomized patients that were followed for up to 27 years after surgery. A modest excess risk of gastric cancer was observed, but the association was inconsistent over gender strata and disappeared over time. Although not discarding the prospect of gastric cancer prevention by eradication of H. pylori, neither do these results unambiguously support the notion that antibiotic treatment reduces the risk of gastric cancer. Highlighting the role of inflammation - possibly H. pylori specific - a protective effect of nonsteroid anti-inflammatory drugs (aspirin) on gastric carcinogenesis was suggested.
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| 9. |
- Fang, Fang, et al.
(författare)
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Stress and cancer : Nordic pieces to the complex puzzle
- 2015
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 30:7, s. 525-527
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Fiorentino, M., et al.
(författare)
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Immunohistochemical Expression of BRCA1 in Prostate Cancer
- 2009
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Ingår i: Laboratory Investigation. - : Nature Publishing Group. - 0023-6837 .- 1530-0307. ; 22, s. 169A-169A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: BRCA1 is a multifunctional protein involved in DNA repair, gene transcription and the regulation of cell-cycle check-points. While germline mutations of BRCA1 are rare in prostate cancer and seem to play a limited role in tumor susceptibility, BRCA1 expression has not been investigated to date.Design: We analyzed the immunohistochemical expression of BRCA1 in paraffin embedded samples from 524 men with prostate cancer belonging to the Physicians’ Health Study and the Swedish Watchful Waiting cohorts of prostate cancer patients. High density tissue micro-arrays (TMA) including at least three tumor cores for each case were utilized for the immunohistochemical staining with the monoclonal MS110 antibody specific for the N-terminus of the 220 kDa BRCA1 protein. Cases were scored as negative or positive for BRCA1 immunostaining. The Ki67 proliferation index was also assessed on the same TMAs and evaluated by quantitative image analysis.Results: A positive nuclear immunostaining for BRCA1 was revealed in 62 of 524 (11.9%) patients while normal prostate control cores were all negative. BRCA1 positive tumors were associated with 4 times greater proliferation rate compared to BRCA1 negative tumors (p ∼ 0.0003). In addition, we found a linear trend such that tumors with greater number of TMA cores expressing BRCA1 had stronger extent of proliferation. Men with BRCA1 positive tumors had a slightly higher Gleason’s score (mean 7.5) compared to those negative for BRCA1 (mean 7) No significant correlation was found between BRCA1 staining and cancer-specific death.Conclusions: BRCA1 protein is expressed in a small subset of prostate cancers characterized by high proliferation index but not in normal prostate tissue. Expression of BRCA1 might be acquired in selected tumors to prevent DNA damage in actively replicating cells. A different role independent of germline mutations might be disclosed for BRCA1 as cell cycle regulator in prostate cancer.
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