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Background: The significant decrease in breast cancer deaths achieved by organized mammography screening programs and treatment of breast cancer at an early phase is a remarkable achievement in clinical cancer research. A remaining challenge is to recognize the breast cancers we are still failing to manage effectively, even when women attend screening regularly and receive modern therapeutic regimens. Many of these fatal tumours originate in the major lactiferous ducts through the carcinogenic process of neoductgenesis with the formation of invasive neoducts. The proposed name for these malignancies is ductal adenocarcinoma of the breast (DAB). Using imaging biomarkers correlated with large format histopathology, we sought to identify the DAB subgroups with the highest fatality.

Method: All histologically proven breast cancer cases (n = 3587) in women of all ages, diagnosed in our Institution from January 2008-June 2022 and followed up through 2023, were prospectively classified into their apparent site of tumour origin using imaging biomarkers mammographic tumour features. These have been correlated with large format histopathology and long-term, patient outcome. Breast cancers originating from the major lactiferous ducts (DAB) formed a subgroup of 570 consecutive cases, which were further subdivided according to their imaging biomarkers. The frequency of occurrence of the combined necrosis producing cases, the combined fluid producing cases and the non-calcified architectural distortion type DAB cases were compared with the death rate within each of these combined subgroups.

Results: Patients with the necrosis-producing DAB subtypes had a significantly elevated, 4.33-fold risk of breast cancer-specific death (95% CI: 1.73–10.84) compared with the fluid-producing DAB subtypes. Patients with the non-calcified architectural distortion DAB subtype had a non-significant 2.51-fold higher risk (95 % CI: 0.87–7.23 compared with the fluid-producing DAB subtypes. The majority of breast cancer deaths, 51/67 (76 %), were in the 317 women having fragmented casting type calcifications on the mammogram. Biopsied axillary node and distant metastases of some fatal cases revealed structures closely resembling neoducts.

Conclusions: Perception and recognition of the imaging biomarkers of the DAB subgroups are necessary first steps in controlling these malignancies, since these biomarkers indicate the site of tumour origin and have documented prognostic value. Reliable imaging-histopathologic correlation of these extensive, diffusely invasive malignancies calls for the use of a large section histopathology technique. The duct-like structures of each DAB subgroup are newly formed invasive neoducts produced by the carcinogenic process of neoductgenesis; they are not pre-existing ducts and can metastasize to the lymph nodes and to distant organs. These observations challenge the use of the term ductal carcinoma in situ (DCIS) for these DAB cases. Until the medical community recognizes that neoductgenesis is an invasive, not an in situ carcinogenic process, we are unlikely to achieve a significant reduction in its high fatality rate.

Serotonin and serotonin metabolism has for decades been understood as playing a critical role in mood disorders and has more recently also been implicated in brain tumour biology. However, in part due to the lack of direct investigation of genetic and epigenetic variation affecting serotonin pathways within human brain tissue this understanding has recently been challenged. We analysed genetic and epigenetic variation in the Monoamine oxidase A (MAOA) and serotonin transporter (5HTT) genes using 232 biobanked glioma tissue samples from 216 adult patients. We further examined the association between use of antidepressants (targeting serotonergic pathways), serotonin levels and methylation. In male patients, genetic variation in the MAOA gene was significantly associated with tissue serotonin levels. Further analysis identified five single nucleotide variants (SNVs) that may contribute to this association. In contrast, 5HTT variants were not statistically associated with serotonin pathway metabolites, nor were MAOA variants in females. Increased methylation at several 5HTT CpG sites was positively correlated with serotonin levels and negatively correlated with 5-HIAA levels. In males, one CpG site in the MAOA gene was negatively associated with the 5-HIAA/serotonin ratio, suggesting reduced enzymatic degradation of serotonin due to lower MAOA activity. Patients using antidepressants had lower tissue serotonin levels. In males, genetic variation in the MAOA gene was significantly associated with tissue serotonin levels, although this association was not mediated by methylation. Our result supports the notion that the MAOA and 5HTT genes are related to serotonin metabolism and that such metabolism is related to antidepressant use.

Objectives: Bruxism significantly affects oral health, with consequences such as tooth wear and restoration failures. Additionally, it is linked to various risk factors and co-occurring disorders. Unlike sleep bruxism, awake bruxism (AB) is more strongly associated with psychosocial factors. This review aimed to evaluate the prevalence of AB in the general population and specific subpopulations.

Methods: The review followed PRISMA guidelines and was registered in PROSPERO (CRD42023398868). A literature search in PubMed, Scopus, and Web of Science until April 8, 2025 identified studies that fulfilled the inclusion criteria of reporting AB prevalence in adult populations. Risk of bias was assessed with Joanna Briggs Institute Prevalence Critical Appraisal Tool and a random-effects meta-analysis determined prevalence in various subpopulations.

Results: The search yielded 8,818 records, with 5,408 abstracts screened after duplicate removal. Of these, 4,473 were excluded. Full-text assessment led to the exclusion of 843 articles that did not meet inclusion criteria. A hand search identified 5 additional studies. Ultimately, 94 studies involving 49,163 individuals were included, with 66 studies (39,823 individuals) analyzed in the meta-analysis. In the general population, self-reported “possible” AB had a mean prevalence of 25.9% (95% CI 22.2-29.9), and clinically based “probable” AB 16.0% (95% CI 10.0-24.5). Prevalence was significantly higher in specific subpopulations, such as individuals with temporomandibular disorders (50.0%, 95% CI 41.1-58.9) and systemic conditions (40.1%, 95% CI 31.4-49.5). Risk of bias was mainly related to assessment of AB.

Conclusions: The variability between subpopulations highlights the importance of considering patient-specific factors and a targeted clinical approach in AB management.

Background: The chemical exposome includes exposure to numerous environmental and endogenous molecules, many of which have been linked to reproductive outcomes due to their endocrine-disrupting properties. As several breast cancer risk factors, including age and parity, are related to reproduction, it is imperative to investigate the interplay between such factors and the chemical exposome prior to conducting large scale exposome-based breast cancer studies.

Objective: This pilot study aimed to provide an overview of the chemical exposome in plasma samples from healthy women and identify associations between environmental exposures and three risk factors for breast cancer: age, parity, and age at menarche.

Material and methods: Plasma samples (n = 161), were selected based on reproductive history from 100 women participating in the Northern Sweden Health and Disease Study, between 1987 and 2006. Samples were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) for 77 priority target analytes including contaminants and hormones, with simultaneous untargeted profiling of the chemical exposome and metabolome. Linear mixed effects models were applied to test associations between risk factors and chemical levels.

Results: Fifty-five target analytes were detected in at least one individual and over 94,000 untargeted features were detected across all samples. Among untargeted features, 430 could be annotated and were broadly classified as environmental (246), endogenous (167) or ambiguous (17). Applying mixed effect models to features detected in at least 70% of the samples (16,778), we found seven targeted analytes (including caffeine and various per- and poly-fluoroalkyl substances) and 38 untargeted features, positively associated with age. The directionality of these associations reversed for parity, decreasing with increasing births. Seven separate targeted analytes were associated with age at menarche.

Significance: This study demonstrates how a comprehensive chemical exposome approach can be used to inform future research prioritization regarding associations between known and unknown substances, reproduction, and breast cancer risk.

Impact statement: This study illustrates how chemical exposomics of long-term stored blood samples offers valuable insights to discover chemical exposures and their potential links to disease in humans, particularly those related to reproduction and breast cancer risk factors.

Purpose: To evaluate current MRI-based criteria for malignancy in mesorectal nodal structures in rectal cancer.

Method: Mesorectal nodal structures identified on baseline MRI as lymph nodes were anatomically compared to their corresponding structures histopathologically, reported as lymph nodes, tumour deposits or extramural venous invasion. All anatomically matched nodal structures from patients with primary surgery and all malignant nodal structures from patients with neoadjuvant treatment were included. Mixed-effects logistic regression models were used to evaluate the morphological criteria irregular margin, round shape, heterogeneous signal and nodal size, as well as the combined 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus criteria, with histopathological nodal status as the gold standard.

Results: In total, 458 matched nodal structures were included from 46 patients (mean age, 67.7 years ± 1.5 [SD], 27 men), of which 19 received neoadjuvant treatment. The strongest associations in the univariable model were found for short-axis diameter ≥ 5 mm (OR 21.43; 95% CI: 4.13–111.29, p < 0.001) and heterogeneous signal (OR 9.02; 95% CI: 1.33–61.08, p = 0.024). Only size remained significant in multivariable analysis (OR 12.32; 95% CI: 2.03–74.57, p = 0.006). When applying the ESGAR consensus criteria to create a binary classification of nodal status, the OR of malignant outcome for nodes with positive ESGAR was 8.23 (95% CI: 2.15–31.50, p = 0.002), with corresponding sensitivity and specificity of 54% and 85%, respectively.

Conclusion: The results confirm the role of morphological and size criteria in predicting lymph node metastases. However, the current criteria might not be accurate enough for nodal staging.

Background: Air pollution has been linked to breast cancer risk, but previous studies have seldom considered specific exposure windows, like pregnancy. During pregnancy the breast undergoes substantial changes and exposures may have a stronger impact than if they occurred during other time periods. This study aims to identify associations between ambient air pollution exposure during pregnancy and risk of early-onset breast cancer.

Methods: Using nationwide data from Swedish registers, we constructed a cohort consisting of all cancer-free women in Sweden giving birth to their first child between 1991 and 2015. Residential exposure to nitrogen dioxide (NO2), particulate matter < 10 μm (PM10) and < 2.5 μm (PM2.5) were modelled based on air pollution concentrations from 2019. Particulate matter between 2.5 and 10 μm (PMcoarse) was calculated separately. Detailed data on residential addresses (including exact moving dates) were available for the entire study period, allowing for spatial variation in the exposure dataset. Mean air pollution levels were assessed at first pregnancy, last pregnancy, 35 years of age, and 2 years after the last delivery. Associations were evaluated using Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Among 1,019,076 women, 12,085 (1.2%) were diagnosed with breast cancer and 65.2% moved at least once between their first pregnancy and two years after their last delivery. All exposures during pregnancy periods were positively associated with breast cancer, with the highest HR observed for exposure to PMcoarse during the last pregnancy (HRPMcoarse = 1.12 (95% CI = 1.04, 1.20) per 5 μg/m3 increase). The lowest HR were for NO2 levels estimated at 35 years of age, regardless of pregnancy status (HRNO2 = 1.03 (95% CI = 0.99, 1.06) per 10 μg/m3 increase). In analyses differentiating between invasive breast cancer and ductal carcinoma in situ, only invasive breast cancer was associated with air pollution exposure.

Conclusions: In this cohort study, air pollution exposure was consistently associated with increased risk of early-onset breast cancer.

OBJECTIVE: Detecting marginal jaw bone loss on radiographs is crucial for diagnosing periodontitis but remains difficult and time-consuming. This review evaluated artificial intelligence (AI) accuracy in identifying the alveolar bone crest and estimating bone loss compared with dental professionals. Moreover, we also assessed whether AI models can detect changes in bone levels over time.

METHODS: We conducted a systematic review in accordance with the PRISMA guidelines, with diagnostic accuracy as the primary outcome. The review protocol was registered in PROSPERO (CRD42024517330). Searches were performed in PubMed, Web of Science, Cochrane, and Scopus up to August 2025. Two independent reviewers screened the articles at the abstract and title levels, and performed full-text and risk-of-bias assessments. A qualitative synthesis was complemented by a random-effects meta-analysis of studies reporting binary classification of marginal bone loss.

RESULTS: Sixty-four studies met the inclusion criteria, with 16 included in the meta-analysis. AI models demonstrated promising performance in detecting the alveolar bone crest and showed high diagnostic accuracy for marginal bone loss, with a pooled sensitivity of 92.3%, a specificity of 91.7%, and an AUC of 0.97. However, high heterogeneity and frequent risk of bias were identified. No study evaluated changes in bone levels over time or was performed in a clinical setting.

CONCLUSION: AI holds promise for facilitating diagnostic decision-making in periodontal care. However, its clinical utility remains limited due to methodological issues. Future research should emphasize external validation, diverse datasets, and longitudinal image analysis to better align AI tools with real-world diagnostic needs.

Multiple myeloma is preceded by monoclonal gammopathy of undetermined significance (MGUS). Only a minority of patients with MGUS will develop multiple myeloma, but precise prediction of progression is impossible using routine clinical biomarkers. Changes in the levels of blood immune markers can help predict disease progression. Data remain inconsistent for some markers of interest such as monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1α), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), fractalkine, and transforming growth factor-alpha (TGF-α). We aimed to investigate the associations between the prediagnostic serum levels of these candidate biomarkers and future multiple myeloma risk, as well as to assess marker changes over time. We performed a nested case-control study using prospective samples from the Janus Serum Bank in Norway to investigate associations between multiple myeloma risk and prediagnostic serum levels of MCP-3, MIP-1α, FGF-2, VEGF, fractalkine, and TGF-α. The study included 293 future multiple myeloma cases with serum samples collected 20 years (median) before multiple myeloma diagnosis and 293 matched cancer-free controls. Patients with multiple myeloma had an additional prediagnostic sample collected up to 42 years before diagnosis to identify marker changes over time. Markers with >60% detection rate (MIP-1α, VEGF, and TGF-α) were included in the statistical analysis. We observed no statistically significant associations between multiple myeloma risk and serum levels of MIP-1α, VEGF, or TGF-α in samples collected 20 years before diagnosis. However, TGF-α levels decreased significantly closer to the diagnosis in patients with multiple myeloma (P < 0.001). The decrease in TGF-α levels may reflect subtle microenvironmental changes related to multiple myeloma progression.

PREVENTION RELEVANCE: This study observed a decline in TGF-α serum levels closer to multiple myeloma diagnosis, which may aid in predicting multiple myeloma progression and early detection, although validation in other longitudinal cohorts is needed.

BACKGROUND AND OBJECTIVES: Temporomandibular disorders (TMDs) is an umbrella term for pain and dysfunction involving jaw muscles and/or the temporomandibular joint, with whiplash trauma suggested to be one risk factor. The aim was to evaluate prevalence and relative risk of TMDs in the acute and chronic stages after whiplash trauma.

DATABASES AND DATA TREATMENT: This review was registered in Prospero (CRD42023407091) and followed the PRISMA guidelines. A literature search in PubMed, Scopus and Web of Science on 10 March 2023 and updated 29 April 2024 identified studies reporting prevalence of TMD after whiplash trauma. Risk of bias was assessed with Joanna Briggs Institute Prevalence Critical Appraisal Tool. A random effect meta-analysis was performed for prevalence of TMD pain.

RESULTS: After screening of 671 identified studies, 96 articles were assessed in full text. Fourteen studies, with 840 cases in the acute and 8293 cases in the chronic stage (i.e., > 3 months post-trauma) were included in a qualitative analysis together with 1591 controls. Nine studies, including 449 cases in the acute and 7912 individuals in the chronic stage after trauma, together with 515 controls, were included in the meta-analysis. Mean prevalence for TMD pain was 18.9% (95% CI 9.71-29.98) in the acute case group, 26.8% (95% CI 15.07-38.79) in the chronic case group, and 5.7% (95% CI 3.08-8.96) in the control group.

CONCLUSIONS: The higher prevalence of TMD pain already in the early stage after whiplash trauma, emphasises the need for early comprehensive clinical assessment as well as targeted research to understand underlying mechanisms.

SIGNIFICANCE: The prevalence of Temporomandibular disorder pain was high already in the acute stage after whiplash trauma, and there was no evidence of any decrease from the acute to the chronic stage. This finding suggests that early assessment and management rather than a 'wait-and see' approach should be recommended when patients present with orofacial pain related to whiplash trauma.

The aim of the present study was to investigate if use of antidepressants is related to the risk of developing lower (WHO grade 2-3) and higher grade (WHO grade 4) glioma. A registry based case-control study was performed using 1283 glioma cases and 6400 age-, sex- and geographically matched controls, diagnosed in Sweden 2009-2013. Conditional logistic regression was used to analyze whether Selective Serotonin Reuptake Inhibitors (SSRIs) or non-SSRIs were associated with the risk of developing lower- or higher-grade glioma in the study population. Our results show that use of antidepressant medication was not associated with the risk of developing glioma. We also performed a meta-analysis in which the dataset from the present study was combined with results from two previous epidemiological studies to answer the same questions. The meta-analysis showed a modest risk reduction of developing glioma in relation to antidepressant treatment (OR 0.90 [95% CI 0.83-0.97]), when all glioma subgroups and all forms of antidepressant medications were combined. In conclusion, it remains possible that antidepressants may have common monoaminergic mechanism(s) that reduce the risk of developing glioma.