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- Wadstrom, Karin, et al.
(författare)
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Associations between plasma metabolism-associated proteins and future development of giant cell arteritis: results from a prospective study
- 2024
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Ingår i: RHEUMATOLOGY. - : Oxford University Press. - 1462-0324 .- 1462-0332.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to investigate the relationship between biomarkers associated with metabolism and subsequent development of GCA. Method Participants in the population-based Malmo Diet Cancer Study (MDCS; N = 30 447) who were subsequently diagnosed with GCA were identified in a structured process. Matched: GCA-free controls were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics metabolism panel (92 metabolic proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explained the variance in the proteome. Results: There were 95 cases with a confirmed incident diagnosis of GCA (median 12.0 years after inclusion). Among biomarkers with a priori hypotheses, adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated [odds ratio (OR) per S.D. 1.67; 95% CI 1.08-2.57], and fructose-1,6-bisphosphatase 1 (FBP1) was negatively associated (OR per S.D. 0.59; 95% CI 0.35-0.99) with GCA. In particular, ADGRE2 levels were associated with subsequent GCA in the subset sampled <8.5 years before diagnosis. For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those patients sampled closest to diagnosis, with a decreasing trend with longer time to GCA (P = 0.03). In the hypothesis-generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA. Conclusion: Biomarkers identified years before clinical diagnosis indicated a protective role of gluconeogenesis (FBP1) and an association with macrophage activation (ADGRE2 and Metrnl) and proinflammatory signals (ROR1) for development of GCA.
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| 4. |
- Wadstrom, H, et al.
(författare)
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Risk of breast cancer before and after rheumatoid arthritis, and the impact of hormonal factors
- 2020
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 79:5, s. 581-586
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Tidskriftsartikel (refereegranskat)abstract
- To examine the risk of incident breast cancer in women with rheumatoid arthritis (RA), and the risk of RA in women with a history of breast cancer, taking antihormonal treatment for breast cancer into account.MethodsUsing nationwide Swedish registers, women with new-onset RA diagnosed in 2006–2016 were identified and analysed using a cohort and a case–control design. Each patient with RA was matched on age, sex and place of residence to five randomly selected subjects from the general population. Through register linkages, we collected information on breast cancer, breast cancer risk factors (reproductive history and hormone replacement therapy) and socio-economy. The relative risk of breast cancer after RA was assessed using Cox regression, and the relative risk of RA in women with a history of breast cancer was assessed using conditional logistic regression.ResultsThe risk of incident breast cancer in women with RA was reduced and the association was not attenuated by adjustment for breast cancer risk factors (HR=0.80, 95% CI 0.68 to 0.93). The risk of RA in women with a history of breast cancer was similarly reduced (OR=0.87, 95% CI 0.79 to 0.95). Women with breast cancer treated with tamoxifen (OR=0.86, 95% CI 0.62 to 1.20) or aromatase inhibitors (OR=0.97, 95% CI 0.69 to 1.37) did not have an increased risk of RA compared with women with breast cancer treated differently.ConclusionsThe decreased occurrence of breast cancer in patients with RA is present already before RA diagnosis; these reduced risks are not readily explained by hormonal risk factors. Adjuvant antihormonal therapy for breast cancer does not seem to increase RA risk.
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| 5. |
- Wadstrom, H, et al.
(författare)
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RISK OF BREAST CANCER BEFORE AND AFTER RHEUMATOID ARTHRITIS, AND THE IMPACT OF HORMONAL FACTORS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 81-81
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Large cohort studies have consistently reported decreased occurrence of breast cancer among women with RA. However, both the reasons behind this decreased risk and if it is present already before RA diagnosis, is unclear. The occurrence of RA following breast cancer is clinically and etiologically important also for other reasons. Long-term adjuvant anti-hormonal treatment with tamoxifen or aromatase inhibitors has become mainstay for estrogen receptor positive breast cancer, but are often associated with arthralgia as a side effect. Some studies have suggested that these therapies not only induce arthralgia, but also inflammatory arthritis.Objectives:To examine the risk of incident breast cancer in women with RA, and the risk of RA in women with a history of breast cancer, taking anti-hormonal treatment for breast cancer into account.Methods:Using nationwide Swedish registers, women with new-onset RA diagnosed 2006-2016 were identified. Each RA patient was matched on age, sex, and place of residence to 5 randomly selected control subjects from the general population. Through register linkages, we collected information on breast cancer, breast cancer risk factors (age at childbirth, number of children, hormone replacement therapy), and socio-economy. The relative risk of breast cancer after RA was assessed using Cox regression, and the relative risk of RA in women with a history of breast was assessed using conditional logistic regression.Results:The risk of incident breast cancer in women with RA was reduced and the association was not attenuated by adjustment for breast cancer risk factors (HR=0.80, 95%CI 0.68-0.93)(Table 1). The risk was similar among seronegative RA, (HR=0.77, 95%CI 0.58-1.02), and seropositive RA, (HR=0.81, 95%CI, 0.67-0.98), and for all age groups. We noted reduced risks for all TNM stages, and for both pre- and postmenopausal breast cancer (assessed with age cutoff 50 years). The risk of RA in women with a history of breast cancer was similarly reduced (OR=0.87, 95%CI, 0.79-0.95). Odds ratios (OR) stratified by serostatus and age at RA diagnosis yielded similar results. There was no clear trend in the level of risk reduction when examining the risk by menopausal status, or cancer stage at breast cancer diagnosis. Women with breast cancer treated with tamoxifen (OR=0.86, 95%CI 0.62-1.20), or aromatase inhibitors (OR=0.97, 95%CI 0.69-1.37), did not have an increased risk of RA compared to women with breast cancer treated differently.Table 1.Risk of breast cancer in women with RA, overall and by serostatus (events and hazard ratios), and risk of RA in women with a history of breast cancer, overall and by serostatus (events and odds ratios)No. of breast cancers, patients with RANo. of breast cancers, comparators/controlsRR (95% CI)Risk of breast cancer in women with RA19011910.80 (0.68-0.93)Seronegative RA553460.77 (0.58-1.02)Seropositive RA1247720.81 (0.67-0.98)Risk of RA in women with breast cancer55531930.87 (0.79-0.95)Seronegative RA1579210.85 (0.71-1.01)Seropositive RA36720880.88 (0.78-0.98)Conclusion:There is a decreased risk of breast cancer in patients with RA, and a similar decrease in risk of breast cancer before RA diagnosis. We did not find evidence to support that the decreased risk of breast cancer was due to known risk determinants. Furthermore, adjuvant anti-hormonal therapy as used in secondary breast cancer pharmacoprevention did not seem to increase the risk of RA.Disclosure of Interests:Hjalmar WADSTRÖM: None declared, Andreas Pettersson: None declared, Karin Ekström Smedby: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma
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