| 31. |
- Larsson, Susanna C., et al.
(författare)
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Assessing the role of cortisol in cancer : a wide-ranged Mendelian randomisation study
- 2021
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 125:7, s. 1025-1029
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Tidskriftsartikel (refereegranskat)abstract
- Background Cortisol’s immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation.Methods Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P < 5 × 10−8) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis.Results A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13–1.99; P = 0.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer.Conclusions These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.
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| 32. |
- Latacz, Emily, et al.
(författare)
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Histopathological growth patterns of liver metastasis : updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights
- 2022
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127:6, s. 988-1013
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Forskningsöversikt (refereegranskat)abstract
- The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.
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| 33. |
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| 34. |
- Lin, E., et al.
(författare)
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Association between atherogenic lipids and GnRH agonists for prostate cancer in men with T2DM : a nationwide, population-based cohort study in Sweden
- 2023
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 128:5, s. 814-824
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGonadotropin-releasing hormone agonists (GnRH) used in prostate cancer (PCa) are associated with atherogenic dyslipidaemia. It can be assumed that GnRH need to be used with greater caution in men with type 2 diabetes mellitus (T2DM). This study investigated association of GnRH with atherogenic lipids (AL) in PCa men with T2DM.MethodsTwo cohorts including 38,311 men with 11 years follow-up based on Swedish national registers were defined (PCa-Exposure cohort and GnRH-Exposure cohort). Based on European guidelines on cardiovascular diseases (CVD), primary outcomes were defined as: 1.0 mmol/L increase in AL and lipid-lowering therapy (LLT) intensification. We used Cox proportional-hazards models and Kaplan–Meier curves to assess the association.ResultsThere was an association between GnRH and increased AL (i.e., triglyceride, PCa-Exposure cohort: HR 1.77, 95% CI 1.48–2.10; GnRH-Exposure cohort: HR 1.88, 95% CI 1.38–2.57). There was also an association between PCa diagnosis and increased AL. In contrast, no association between LLT intensification and GnRH was found.ConclusionIn this large population-based study, men with T2DM on GnRH for PCa had an increased risk of increased atherogenic lipids. These results highlight the need to closely monitor lipids and to be ready to intensify lipid-lowering therapy in men with T2DM on GnRH for PCa.
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| 35. |
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| 36. |
- Lundberg, Peter, 1958-, et al.
(författare)
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Breast density is strongly associated with multiparametric magnetic resonance imaging biomarkers and pro-tumorigenic proteins in situ
- 2022
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127, s. 2025-2033
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Tidskriftsartikel (refereegranskat)abstract
- Background High mammographic density is an independent risk factor for breast cancer by poorly understood molecular mechanisms. Women with dense breasts often undergo conventional magnetic resonance imaging (MRI) despite its limited specificity, which may be increased by diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) and contrast. How these modalities are affected by breast density per se and their association with the local microenvironment are undetermined. Methods Healthy postmenopausal women attending mammography screen with extremely dense or entirely fatty breasts underwent multiparametric MRI for analyses of lean tissue fraction (LTF), ADC and perfusion dynamics. Microdialysis was used for extracellular proteomics in situ. Results Significantly increased LTF and ADC and delayed perfusion were detected in dense breasts. In total, 270 proteins were quantified, whereof 124 related to inflammation, angiogenesis, and cellular growth were significantly upregulated in dense breasts. Most of these correlated significantly with LTF, ADC and the perfusion data. Conclusions ADC and perfusion characteristics depend on breast density, which should be considered during the implementation of thresholds for malignant lesions. Dense and nondense breasts are two essentially different biological entities, with a pro-tumorigenic microenvironment in dense breasts. Our data reveal several novel pathways that may be explored for breast cancer prevention strategies.
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| 37. |
- Matikas, A, et al.
(författare)
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Detection of circulating tumour cells before and following adjuvant chemotherapy and long-term prognosis of early breast cancer
- 2022
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 126:11, s. 1563-1569
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe detection of circulating tumour cells (CTC) is prognostic for disease recurrence in early breast cancer (BC). This study aims to investigate whether this prognostic effect persists or varies over time.MethodsThe study population consisted of prospectively included stage I–III BC patients. The presence ofCK19mRNA-positive CTC in the peripheral blood was evaluated before and after adjuvant chemotherapy, using a real-time RT–PCR assay. Longitudinal samples were collected for a subset of patients.ResultsBaseline CTC data were available from 1220 patients, while 1132 had both pre- and post-therapy data. After a median follow-up of 134.1 months, CTC positivity at baseline was associated with shorter overall survival (OS; HRadj = 1.72, 95% CI 1.34–2.21,p < 0.001). For disease-free survival, an interaction with time (p = 0.045) was observed. CTC positivity predicted early (within 5 years; HRadj = 1.76, 95%CI 1.33–2.32,p < 0.001) but not late recurrence (HRadj = 1.10, 95% CI 0.79–1.53,p = 0.577). Following adjuvant chemotherapy, more patients converted from CTC-positive to CTC-negative than vice versa (p < 0.001). Ten-year OS was 68.6% for + /+ and 86.7% for −/− group (p < 0.001). CTC status at follow-up predicted disease recurrence.ConclusionCTC detection pre- and post-adjuvant chemotherapy is prognostic for early relapse, supporting investigations for novel adjuvant therapeutic approaches.
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| 38. |
- Matikas, A, et al.
(författare)
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Response to A. Chauhan and A. Pal
- 2022
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 126:11, s. 1661-1662
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 39. |
- Mogensen, Hanna, et al.
(författare)
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Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden
- 2024
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Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 130:2, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- Background: Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation.Methods: From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0–14 years in 1971–2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI).Results: Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (ORSurv_PopComp2.05, 95%CI: 1.83–2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay.Conclusions: Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers.
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| 40. |
- Morken, Siren, et al.
(författare)
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Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms.
- 2023
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Ingår i: British journal of cancer. - 0007-0920 .- 1532-1827. ; 129:12, s. 1930-1939
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Tidskriftsartikel (refereegranskat)abstract
- The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy andsafety of everolimus and temozolomide as first-line treatment for these patients.Patients received everolimus 10mg daily continuously and temozolomide 150mg/m2 for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed.For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%, the median progression-free survival (PFS) 10.2months and the median overall survival (OS) 26.4months. Considering 26 NET G3 patients, 6months DCR was 77% vs. 22% among nine NEC patients (p=0.006). PFS was superior for NET G3 vs. NEC (12.6months vs. 3.4months, Log-rank-test: p=0.133, Breslow-test: p<0.001). OS was significantly better for NET G3 (31.4months vs. 7.8months, p=0.003). Grade 3 and 4 toxicities were reported in 43% and 38%. QoL remained stable during treatment.Everolimus and temozolomide may be a treatment option for selected GEP-NET G3 patients including careful monitoring. Toxicity did not compromise QoL.ClinicalTrials.gov (NTC02248012).
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