| 1. |
- Brandt, Jasmine, et al.
(författare)
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Age at diagnosis in relation to survival following breast cancer: a cohort study.
- 2015
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Ingår i: World Journal of Surgical Oncology. - : Springer Science and Business Media LLC. - 1477-7819. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Age is an important risk factor for breast cancer, but previous data has been contradictory on whether patient age at diagnosis is also related to breast cancer survival. The present study evaluates age at diagnosis as a prognostic factor for breast cancer on a large cohort of patients at a single institution.
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| 2. |
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| 3. |
- Brandt, Jasmine, et al.
(författare)
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Thyroid-associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:7, s. 1309-1321
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.
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| 4. |
- Brandt, Jasmine
(författare)
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Thyroid function and breast cancer. Risk and clinical outcome in relation to thyroid hormones (free T3/T4), TSH, TPO-Antibodies and genetic variants.
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Thyroid hormone level has been positively associatedwith breast cancer cell proliferation andtumour growth in experimental studies. However,previous observational studies have been contradictoryon the relationship between thyroidfunction and breast cancer. Age is a known riskfactor for breast cancer but its role as a prognosticfactor is less clear. The present thesis thereforeaimed to examine the contradictory relation betweenthyroid function and breast cancer risk,progression and survival. Also, age at breast cancerdiagnosis was evaluated as a prognostic factor.The first paper was a baseline study on theinfluence of age at diagnosis on breast cancermortality in different diagnostic periods (follow-upuntil 2001). The study was conductedon 4,453 women diagnosed with breast cancer.We found that women under 40 years of age hada poor prognosis, and this association seemedto be strongest among young women with axillarylymph node negative breast cancer. Furthermore,an age of 80 years or more was a prognosticfactor for poor survival, independent of stageat diagnosis and diagnostic period.The second paper evaluated pre-diagnosticlevels of free triiodothyronine (free T3), freethyroxine (free T4), thyroid-stimulating hormone(TSH), and thyroid peroxidase antibodies(TPO-Ab) in relation to breast cancer subgroupsand aggressiveness. The cohort used wasthe Malmö Diet and Cancer Study, which is apopulation based cohort of 17,035 women recruitedbetween 1991 and 1996. Our resultsindicated that high pre-diagnostic free T4 levelsand low pre-diagnostic TPO-Ab levels wereassociated with an increased risk of breast cancer.This increase was mainly limited to a higherincidence rate of less aggressive forms of breastcancer.In the third paper we examined if the effect ofthyroid function on breast cancer subgroups alsoinfluenced breast cancer survival. We displayeda positive association between free T4 levels andan improved breast cancer survival.The possible effect of genetic markers for freeT4 and TPO-Ab on breast cancer risk was assessedin the fourth paper. We identified fivemarkers that influenced the risk of breast cancer,of which rs2235544 (D101 gene) was the mostinteresting. This was the first study to suggestan association between thyroid-related geneticvariants and breast cancer risk.The potential association between thyroidfunction and breast cancer is complex, as it exertsits effect through several pathways. This thesishas contributed to our understanding of howthyroid function influences breast cancer riskand breast cancer mortality. In addition, it hasenlightened the importance of age at diagnosisas a prognostic factor.
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| 5. |
- Dwibedi, Chinmay, 1987, et al.
(författare)
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Randomized open-label trial of semaglutide and dapagliflozin in patients with type 2 diabetes of different pathophysiology
- 2024
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Ingår i: Nature Metabolism. - 2522-5812. ; 6:1, s. 50-60
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Tidskriftsartikel (refereegranskat)abstract
- The limited understanding of the heterogeneity in the treatment response to antidiabetic drugs contributes to metabolic deterioration and cardiovascular complications 1,2, stressing the need for more personalized treatment 1. Although recent attempts have been made to classify diabetes into subgroups, the utility of such stratification in predicting treatment response is unknown 3. We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD). Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium–glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label). The primary endpoint was the change in glycated haemoglobin (HbA1c). Semaglutide induced a larger reduction in HbA1c levels than dapagliflozin (mean difference, 8.2 mmol mol−1; 95% confidence interval, −10.0 to −6.3 mmol mol−1), with a pronounced effect in those with SIDD. No difference in adverse events was observed between participants with SIDD and those with SIRD. Analysis of secondary endpoints showed greater reductions in fasting and postprandial glucose concentrations in response to semaglutide in participants with SIDD than in those with SIRD and a more pronounced effect on postprandial glucose by dapagliflozin in participants with SIDD than in those with SIRD. However, no significant interaction was found between drug assignment and the SIDD or SIRD subgroup. In contrast, continuous measures of body mass index, blood pressure, insulin secretion and insulin resistance were useful in identifying those likely to have the largest improvements in glycaemic control and cardiovascular risk factors by adding semaglutide or dapagliflozin. Thus, systematic evaluation of continuous pathophysiological variables can guide the prediction of the treatment response to these drugs and provide more information than stratified subgroups (NCT04451837).
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| 6. |
- Huss, Linnea, et al.
(författare)
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SNPs related to vitamin D and breast cancer risk : A case-control 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: It has been suggested that vitamin D might protect from breast cancer, although studies on levels of vitamin D in association with breast cancer have been inconsistent. Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) to be associated with vitamin D. The aim of this study was to investigate such vitamin D-SNP associations in relation to subsequent breast cancer risk. A first step included verification of these SNPs as determinants of vitamin D levels. Methods: The Malmö Diet and Cancer Study included 17,035 women in a prospective cohort. Genotyping was performed and was successful in 4058 nonrelated women from this cohort in which 865 were diagnosed with breast cancer. Levels of vitamin D (25-hydroxyvitamin D) were available for 700 of the breast cancer cases and 643 of unaffected control subjects. SNPs previously associated with vitamin D in GWASs were identified. Logistic regression analyses yielding ORs with 95% CIs were performed to investigate selected SNPs in relation to low levels of vitamin D (below median) as well as to the risk of breast cancer. Results: The majority of SNPs previously associated with levels of vitamin D showed a statistically significant association with circulating vitamin D levels. Heterozygotes of one SNP (rs12239582) were found to have a statistically significant association with a low risk of breast cancer (OR 0.82, 95% CI 0.68-0.99), and minor homozygotes of the same SNP were found to have a tendency towards a low risk of being in the group with low vitamin D levels (OR 0.72, 95% CI 0.52-1.00). Results from stratified analyses showed diverse associations with breast cancer risk for a few of the tested SNPs, depending on whether vitamin D level was high or low. Conclusions: SNPs associated with vitamin D may also be associated with the risk of breast cancer. Even if such a risk is small, the allele frequency of the SNP variants is high, and therefore the population attributable risk could be substantial. It is also possible that vitamin D levels may interact with genomic traits with regard to breast cancer risk.
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| 7. |
- Sartor, Hanna, et al.
(författare)
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The association of single nucleotide polymorphisms (SNPs) with breast density and breast cancer survival : the Malmö Diet and Cancer Study
- 2020
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 61:10, s. 1326-1334
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic factors are important in determining breast density, and heritable factors account for 60% of the variation. Certain single nucleotide polymorphisms (SNPs) are associated with density and risk of breast cancer but the association with prognosis is not clear. Purpose: To investigate associations between selected SNPs and breast cancer survival in the Malmö Diet and Cancer Study (MDCS). Material and Methods: A total of 724 unrelated women with breast cancer and registered radiological and pathological data were identified in MDCS 1991–2007, with genotyping available for 672 women. Associations among 15 SNPs, density, and breast cancer-specific survival were analyzed using logistic/Cox regression, adjusted for factors affecting density and survival. Variants significantly associated with either density or survival were validated in a large independent breast cancer cohort (LIBRO-1). Results: Minor homozygotes of SNPs rs9383589, CCDC170 and rs6557161, ESR1 were associated with high breast density (adjusted odds ratio [AOR] 8.97, 95% confidence interval [CI] 1.35–59.57; AOR 2.08, 95% CI 1.19–3.65, respectively) and poorer breast cancer survival (adjusted hazard ratio [HRadj] 6.46, 95% CI 1.95–21.39; HRadj 2.30, 95% CI 1.33–3.96, respectively) compared to major homozygotes. For SNP rs3757318, ESR1, minor homozygotes (HRadj 7.46, 95% CI 2.28–24.45) were associated with poorer survival. We confirmed that rs6557161, ESR1 was significantly associated with both density and survival in the LIBRO-1 study. Conclusion: These findings support a shared genetic basis for density and breast cancer survival. The SNP significantly associated with both density and survival in both cohorts may be of interest in future research investigating polygenic risk scores for breast cancer risk and screening stratification purposes.
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