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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 4. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 5. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 6. |
- Jiao, Xiang, et al.
(författare)
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PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
- 2017
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:61, s. 102769-102782
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Tidskriftsartikel (refereegranskat)abstract
- Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
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| 7. |
- van Kuilenburg, Andre B. P., et al.
(författare)
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Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 380:15, s. 1433-1441
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Tidskriftsartikel (refereegranskat)abstract
- We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5′ untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing.
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| 8. |
- Borgquist, Signe, et al.
(författare)
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Long-term exposure to insulin and volumetric mammographic density : Observational and genetic associations in the Karma study
- 2018
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long-term insulin exposure has been implicated in breast cancer etiology, but epidemiological evidence remains inconclusive. The aims of this study were to investigate the association of insulin therapy with mammographic density (MD) as an intermediate phenotype for breast cancer and to assess associations with long-term elevated circulating insulin levels using a genetic score comprising 18 insulin-associated variants. Methods: We used data from the KARolinska MAmmography (Karma) project, a Swedish mammography screening cohort. Insulin-treated patients with type 1 (T1D, n = 122) and type 2 (T2D, n = 237) diabetes were identified through linkage with the Prescribed Drug Register and age-matched to 1771 women without diabetes. We assessed associations with treatment duration and insulin glargine use, and we further examined MD differences using non-insulin-treated T2D patients as an active comparator. MD was measured using a fully automated volumetric method, and analyses were adjusted for multiple potential confounders. Associations with the insulin genetic score were assessed in 9437 study participants without diabetes. Results: Compared with age-matched women without diabetes, insulin-treated T1D patients had greater percent dense (8.7% vs. 11.4%) and absolute dense volumes (59.7 vs. 64.7 cm3), and a smaller absolute nondense volume (615 vs. 491 cm3). Similar associations were observed for insulin-treated T2D, and estimates were not materially different in analyses comparing insulin-treated T2D patients with T2D patients receiving noninsulin glucose-lowering medication. In both T1D and T2D, the magnitude of the association with the absolute dense volume was highest for long-term insulin therapy (≥ 5 years) and the long-acting insulin analog glargine. No consistent evidence of differential associations by insulin treatment duration or type was found for percent dense and absolute nondense volumes. Genetically predicted insulin levels were positively associated with percent dense and absolute dense volumes, but not with the absolute nondense volume (percentage difference [95% CI] per 1-SD increase in insulin genetic score = 0.8 [0.0; 1.6], 0.9 [0.1; 1.8], and 0.1 [- 0.8; 0.9], respectively). Conclusions: The consistency in direction of association for insulin treatment and the insulin genetic score with the absolute dense volume suggest a causal influence of long-term increased insulin exposure on mammographic dense breast tissue.
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| 9. |
- Brand, Judith S., et al.
(författare)
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Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:4, s. 1012-1019
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.RESEARCH DESIGN AND METHODS-Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied.RESULTS-Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and >= 55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [ 1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05).CONCLUSIONS-Early menopause is associated with a greater risk of type 2 diabetes. Diabetes Care 36:1012-1019, 2013
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| 10. |
- Brand, Judith S, et al.
(författare)
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Chemotherapy, genetic susceptibility, and risk of venous thromboembolism in breast cancer patients
- 2016
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Ingår i: Clinical Cancer Research. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1078-0432. ; 22:21, s. 5249-5255
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Venous thromboembolism (VTE) is highly heritable and a serious complication of cancer and its treatment. We examined the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk in patients with breast cancer. Experimental design: A Swedish population-based study including 4,261 women diagnosed with primary invasive breast cancer between 2001 and 2008 in Stockholm, followed until 2012. Risk stratification by chemotherapy and genetic susceptibility [a polygenic risk score (PRS), including nine established VTE loci] was assessed using Kaplan-Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics. Results: In total, 276 patients experienced a VTE event during a median follow-up of 7.6 years. Patients receiving chemotherapy [HR (95% CI) = 1.98; 1.40-2.80] and patients in the highest 5% of the PRS [HR (95% CI) = 1.90; 1.24-2.91] were at increased risk of developing VTE. Chemotherapy and PRS acted independently on VTE risk and the 1-year cumulative incidence in patients carrying both risk factors was 9.5% compared with 1.3% in patients not having these risk factors (P < 0.001). Stratified analyses by age showed that the risk-increasing effect of PRS was stronger in older patients (P interaction = 0.04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%). Conclusions: Risk stratification by chemotherapy and genetic susceptibility identifies patients with breast cancer at high VTE risk, who could potentially benefit from thromboprophylaxis. Our results further suggest that genetic testing is more informative in older patients with breast cancer.
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| 11. |
- Brand, Judith S, et al.
(författare)
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Infection-related hospitalizations in breast cancer patients : risk and impact on prognosis
- 2016
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Ingår i: Journal of Infection. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0163-4453 .- 1532-2742.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Infections are a common cause of hospitalization in breast cancer patients. We studied the risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population. METHODS: A Swedish registry-based study including 8338 breast cancer patients diagnosed between 2001 and 2008, followed prospectively for infection-related hospitalizations until 2010. Standardized incidence ratios (SIRs) were calculated using background rates from the general female population. Associations with clinical characteristics and mortality were analyzed using flexible parametric survival models. RESULTS: In total, 720 patients experienced an infection-related hospitalization during a median follow-up of 4.9 years. Infection rates were highest within the first year of diagnosis (SIR = 5.61, 95% CI; 4.98-6.32), and site-specific risks were most pronounced for sepsis (SIR = 3.14, 95% CI; 2.66-3.71) and skin infections (SIR = 2.80, 95% CI; 2.24-3.50). Older age at diagnosis, comorbidities, markers of tumor aggressiveness, chemotherapy and axillary node dissection were independent predictors of infectious disease risk. Infection-related hospitalizations were also independently associated with overall and breast cancer-specific death. CONCLUSIONS: A significant number of breast cancer patients are hospitalized with an infection following diagnosis, which in turn predicts poor prognosis. The risk profile of infection-related hospitalizations is multifactorial, including patient, tumor and treatment-related factors.
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| 12. |
- Brand, Judith S, et al.
(författare)
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Risk of serious infections in multiple sclerosis patients by disease course and disability status : Results from a Swedish register-based study
- 2022
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Ingår i: Brain, behavior, & immunity - health. - : Elsevier. - 2666-3546. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: Serious infections are an emerging concern with increasing use of potent immunomodulation in multiple sclerosis (MS), but the extent to which MS disease features influence infectious susceptibility is poorly characterized. The objective of this study was to assess the associations of MS disease course and disability status with risk of serious infections.Methods: A cohort of 8660 MS patients was individually matched on age, sex and region of residence with 86,600 people without MS from the general population using national registers in Sweden. The study period was from 1996 to 2012, with follow-up until December 31, 2014. The main outcomes were infection as the underlying or contributory cause of death or infection-related hospital admission identified in the Cause of Death and Patient registers. MS disease course (relapsing-remitting or progressive disease) and Expanded Disability Status Scale (EDSS) score (six and over or below six) were extracted from the MS Register Hazard ratios (HRs) for any serious infection were estimated using flexible parametric models.Results: During a median follow-up of 9.6 years (interquartile range = 5.5-13.5 years), 1337 MS patients experienced a serious infection. Compared with individually matched people without MS, risk of serious infection was greater for progressive disease (HR = 3.80; 95% CI 3.52: 4.09) than relapsing-remitting disease (HR = 1.77; 95% CI: 1.62:1.93). A similar pattern of risk was seen for dichotomised EDSS score (HR = 4.26; 95% CI 3.87: 4.70 for EDSS 6.0-9.5 and HR = 1.30; 95% CI 1.1853: 1.43 for EDSS 0.0-5.5). Overall, associations with greater disability did not notably differ by immunomodulatory therapy use, but associations with lower disability were more pronounced in patients receiving these therapies.Conclusions: Disease course or EDSS score (which may be more readily available than MS course in some patients) should be considered in individual management and monitoring of MS patients, including assessing benefit-risk of therapies that influence general immune function.
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| 13. |
- Brand, Judith S, et al.
(författare)
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Time-dependent risk and predictors of venous thromboembolism in breast cancer patients: a population-based cohort study
- 2016
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Ingår i: Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0008-543X .- 1097-0142.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Venous thromboembolism (VTE) is a serious complication of cancer and its treatment. The current study assessed the risk and clinical predictors of VTE in breast cancer patients by time since diagnosis. METHODS: This Swedish population-based study included 8338 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region with complete follow-up until 2012. Their incidence of VTE was compared with the incidence among 39,013 age-matched reference individuals from the general population. Cox and flexible parametric models were used to examine associations with patient, tumor, and treatment characteristics, accounting for time-dependent effects. RESULTS: Over a median follow-up of 7.2 years, 426 breast cancer patients experienced a VTE event (cumulative incidence, 5.1%). The VTE incidence was 3-fold increased (hazard ratio [HR], 3.28; 95% confidence interval [CI], 2.87-3.74) in comparison with the incidence in the general population and was highest 6 months after diagnosis (HR, 8.62; 95% CI, 6.56-11.33) with a sustained increase in risk thereafter (HR at 5 years, 2.19; 95% CI, 1.80-2.67). Independent predictors of VTE included the following: older age, being overweight, preexisting VTE, comorbid disease, tumor size > 40 mm, progesterone receptor (PR)-negative status, more than 4 affected lymph nodes, and receipt of chemo- and endocrine therapy. The impact of chemotherapy was limited to early-onset VTE, whereas comorbid disease and PR-negative status were more strongly associated with late-onset events. CONCLUSIONS: This study confirms the long-term risk of VTE in breast cancer patients and identifies a comprehensive set of clinical risk predictors. Temporal associations with patient, tumor, and treatment characteristics provide insight into the time-dependent etiology of VTE.
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| 14. |
- Colzani, Edoardo, et al.
(författare)
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Risk of hospitalization and death due to bone fractures after breast cancer: a registry-based cohort study
- 2016
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Ingår i: British Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0007-0920 .- 1532-1827.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. METHODS: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. RESULTS: For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23-1.28) and 1.18 (95% CI: 1.14-1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index 1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98-2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50-2.22) compared with those without bone fracture. CONCLUSIONS: Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.
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| 15. |
- Elks, Cathy E., et al.
(författare)
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Age at Menarche and Type 2 Diabetes Risk The EPIC-InterAct study
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 36:11, s. 3526-3534
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEYounger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity.RESEARCH DESIGN AND METHODSThe prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI.RESULTSMean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m(2) lower adult BMI. Women in the earliest menarche quintile (8-11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49-1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18-1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes.CONCLUSIONSWomen with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.
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| 16. |
- Hedayati, E., et al.
(författare)
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Outcome and presentation of heart failure in breast cancer patients : Findings from a Swedish register-based study
- 2020
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press. - 2058-5225 .- 2058-1742. ; 6:2, s. 147-155
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Heart failure (HF) patients diagnosed with breast cancer (BC) may have a higher risk of death, and different HF presentation and treatment than patients without BC.Methods and results: A total of 14 998 women with incident HF (iHF) or prevalent HF (pHF) enrolled in the Swedish HF Registry within and after 1 month since HF diagnosis, respectively, between 2008 and 2013. Patients were linked with the National Patient-, Cancer-, and Cause-of-Death Registry. Two hundred and ninety-four iHF and 338 pHF patients with BC were age-matched to 1470 iHF and 1690 pHF patients without BC. Comorbidity and treatment characteristics were compared using the χ2 tests for categories. Cox proportional hazard models assessed the hazard ratio (HR) and 95% confidence intervals (95% CIs) of all-cause and cardiovascular mortality among HF patients with and without BC. In the pHF group, BC patients had less often myocardial infarction (21.6% vs. 28.6%, P < 0.01) and received less often aspirin (47.6% vs. 55.1%, P = 0.01), coronary revascularization (11.8% vs. 16.2%, P < 0.01), or device therapy (0.9% vs. 3.0%, P = 0.03). After median follow-up of 2 years, risk of all-cause mortality (iHF: HR = 1.04, 95% CI = 0.83-1.29 and pHF: HR = 0.94, 95% CI = 0.79-1.12), cardiovascular mortality (iHF: HR = 0.94, 95% CI = 0.71-1.24 and pHF: HR = 0.89, 95% CI = 0.71-1.10), and HF mortality (iHF: HR = 0.80, 95% CI = 0.34-1.90 and pHF: HR = 0.75, 95% CI = 0.43-1.29) were similar for patients with and without BC in the iHF and pHF groups.Conclusion: Risk of all-cause and cardiovascular mortality in HF patients did not differ by BC status. Differences in pre-existing myocardial infarction and HF treatment among pHF patients with and without BC may suggest differences in pathogenesis of HF.
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| 17. |
- Shrestha, Sarita, 1991-, et al.
(författare)
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Association between inflammatory bowel disease and spondyloarthritis : findings from a nationwide study in Sweden
- 2022
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479 .- 1197-4982. ; 16:1, s. 1540-1550
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been associated with spondyloarthritis (SpA), but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD to the general population, overall and by IBD subtype and age.METHODS: We used a nationwide register-based cohort study of 39,203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390,490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios (ORs) for a prior (prevalent) SpA diagnosis and conditional Cox regression to calculate hazard ratios (HRs) for a subsequent (incident) SpA diagnosis in IBD patients.RESULTS: IBD patients were more likely to have prevalent SpA at IBD diagnosis (2.5%) compared to reference individuals (0.7%) with an OR of 3.48 (95%CI:3.23-3.75). They also more often received an incident diagnosis of SpA; during 23,341,934 person-years of follow-up in IBD patients, there were 1,030 SpA events (5.0/1,000 person-years) compared to 1,524 SpA events in the reference group (0.72/1,000 person-years), corresponding to an HR of 7.15 (95%CI:6.60-7.75). In subgroup analyses, associations were most pronounced among patients with Crohn's disease [(OR=5.20; 95%CI:4.59-5.89), and (HR=10.55; 95%CI:9.16-12.15)] and paediatric onset IBD [(OR=3.63; 95%CI:2.35-5.59) and (HR=15.03; 95%CI:11.01-20.53)].CONCLUSION: IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared to the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity across IBD subtypes and age-groups, calls for targeted approaches to facilitate timely diagnosis and intervention.
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| 18. |
- Shrestha, Sarita, 1991-, et al.
(författare)
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Spondyloarthritis in first-degree relatives and spouses of patients with inflammatory bowel disease : A nationwide population-based cohort study from Sweden
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals.METHODS: We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA.RESULTS: During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses.CONCLUSIONS: The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.
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| 20. |
- Trinh, Thang, et al.
(författare)
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Background risk of breast cancer and the association between physical activity and mammographic density
- 2015
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Ingår i: Breast Cancer Research. - : BIOMED CENTRAL LTD. - 1465-5411 .- 1465-542X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction High physical activity has been shown to decrease the risk of breast cancer, potentially by a mechanism that also reduces mammographic density. We tested the hypothesis that the risk of developing breast cancer in the next 10 years according to the Tyrer-Cuzick prediction model influences the association between physical activity and mammographic density. Methods We conducted a population-based cross-sectional study of 38,913 Swedish women aged 4074 years. Physical activity was assessed using the validated web-questionnaire Active-Q and mammographic density was measured by the fully automated volumetric Volpara method. The 10-year risk of breast cancer was estimated using the Tyrer-Cuzick (TC) prediction model. Linear regression analyses were performed to assess the association between physical activity and volumetric mammographic density and the potential interaction with the TC breast cancer risk. Results Overall, high physical activity was associated with lower absolute dense volume. As compared to women with the lowest total activity level (<40 metabolic equivalent hours [MET-h] per day), women with the highest total activity level (>= 50 MET-h/day) had an estimated 3.4 cm(3) (95% confidence interval, 2.3-4.7) lower absolute dense volume. The inverse association was seen for any type of physical activity among women with <3.0% TC 10-year risk, but only for total and vigorous activities among women with 3.0-4.9% TC risk, and only for vigorous activity among women with >= 5.0% TC risk. The association between total activity and absolute dense volume was modified by the TC breast cancer risk (P-interaction = 0.05). As anticipated, high physical activity was also associated with lower non-dense volume. No consistent association was found between physical activity and percent dense volume. Conclusions Our results suggest that physical activity may decrease breast cancer risk through reducing mammographic density, and that the physical activity needed to reduce mammographic density may depend on background risk of breast cancer.
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- Yang, Haomin, et al.
(författare)
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Risk and predictors of psoriasis in patients with breast cancer : a Swedish population-based cohort study
- 2017
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The risk of psoriasis in patients with breast cancer is largely unknown, as available evidence is limited to case findings. We systematically examined the incidence and risk factors of psoriasis in patients with breast cancer.METHODS: A Swedish nationwide cohort of 56,235 breast cancer patients (2001-2012) was compared to 280,854 matched reference individuals from the general population to estimate the incidence and hazard ratio (HR) of new-onset psoriasis. We also calculated HRs for psoriasis according to treatment, genetic, and lifestyle factors in a regional cohort of 8987 patients.RESULTS: In the nationwide cohort, 599 patients with breast cancer were diagnosed with psoriasis during a median follow-up of 5.1 years compared to 2795 cases in the matched reference individuals. This corresponded to an incidence rate of 1.9/1000 person-years in breast cancer patients vs. 1.7/1000 person-years in matched reference individuals. Breast cancer patients were at an increased risk of psoriasis (HR = 1.17; 95% confidence interval (CI) = 1.07-1.28), especially its most common subtype (psoriasis vulgaris; HR = 1.33; 95% CI = 1.17-1.52). The risk of psoriasis vulgaris was highest shortly after diagnosis but remained increased up to 12 years. Treatment-specific analyses indicated a higher risk of psoriasis in patients treated with radiotherapy (HR = 2.44; 95% CI = 1.44-4.12) and mastectomy (HR = 1.54, 95% CI = 1.03-2.31). Apart from treatment-specific effects, we identified genetic predisposition, obesity, and smoking as independent risk factors for psoriasis in breast cancer patients.CONCLUSIONS: The incidence of psoriasis is slightly elevated among patients with breast cancer, with treatment, lifestyle, and genetic factors defining the individual risk profile.
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| 23. |
- Yang, Haomin, et al.
(författare)
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Risk of heart disease following treatment for breast cancer - results from a population-based cohort study
- 2022
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure, and ischemic heart disease in women diagnosed with breast cancer.Methods: A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region and followed up until 2017. Time-dependent risks of arrhythmia, heart failure, and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.Results: Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR = 1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following locoregional radiotherapy.Conclusions: Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices.
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| 24. |
- Yang, Haomin, et al.
(författare)
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Time-dependent risk of depression, anxiety, and stress-related disorders in patients with invasive and in situ breast cancer
- 2017
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress-related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in-situ breast cancer (2001- 2010, median follow-up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001-2013, median follow-up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress-related disorders [overall SIR (95% CI) = 1.57 (1.46- 1.69), 1.55 (1.43-1.68) and 1.77 (1.60-1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher-grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher-grade disease conferring short-term risk only, while comorbidities were mainly associated with late-onset events. No clinical risk factors were identified for stress-related disorders except for a greater risk associated with younger age. Patients with in-situ cancer only showed an increased incidence of stress-related disorders during the first six months after diagnosis [SIR (95% CI) = 2.76 (1.31-5.79)]. The time-dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho-oncologic interventions.
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