| 11. |
- Enroth, Linda, et al.
(författare)
-
Changes in socioeconomic differentials in old age life expectancy in four Nordic countries : the impact of educational expansion and education-specific mortality
- 2022
-
Ingår i: European Journal of Ageing. - : Springer Science and Business Media LLC. - 1613-9372 .- 1613-9380. ; 19:2, s. 161-173
-
Tidskriftsartikel (refereegranskat)abstract
- Overall progress in life expectancy (LE) depends increasingly on survival in older ages. The birth cohorts now reaching old age have experienced considerable educational expansion, which is a driving force for the social change and social inequality. Thus, this study examines changes in old age LE by educational attainment in the Nordic countries and aims to fnd out to what extent the change in national LEs is attributable to education-specifc mortality and the shifting educational composition. We used national register data comprising total 65+populations in Denmark, Finland, Norway and Sweden to create period life tables stratifed by fve-year age groups (65–90+), sex and educational attainment. Difference in LE between 2001 and 2015 was decomposed into the contributions of mortality changes within each educational group and changes in educational composition. Increasing LE at all ages and in all educational groups coincided with persistent and growing educational inequalities in all countries. Most of the gains in LE at age 65 could be attributed to decreased mortality (63–90%), especially among those with low education, the largest educational group in most countries. The proportion of the increase in LE attributable to improved education was 10–37%, with the highest contributions recorded for women in Norway and Sweden. The rising educational levels in the Nordic countries still carry potential for further gains in national LEs. However, the educational expansion has contributed to uneven gains in LE between education groups, which poses a risk for the future increase of inequalities in LE.
|
|
| 12. |
- Enroth, Linda, et al.
(författare)
-
Trends in the Social Class Inequalities in Disability and Self-Rated Health : Repeated Cross-Sectional Surveys from Finland and Sweden 2001-2018
- 2021
-
Ingår i: International Journal of Public Health. - : Frontiers Media SA. - 1661-8556 .- 1661-8564. ; 66
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess time trends in the social class inequalities and in total inequality in disability and self-rated health (SRH) in two oldest old populations.Methods: The data came from the Finnish Vitality 90+ Study (2001, 2003, 2007, 2010, 2014 and 2018; n = 5,440) and from the Swedish Panel Study of Living Conditions of the Oldest Old (2002, 2004, 2011 and 2014; n = 1,645). Inequalities in mobility and activities of daily living (ADL) disability and SRH were examined cross-sectionally and over time using relative and absolute measures.Results: Lower social classes had greater mobility and ADL disability and worse SRH than higher social classes and the inequalities tended to increase over time. Findings were remarkably similar in both studies and with absolute and relative measures. Total inequality, referring to the variance in health outcome in the total population, remained stable or decreased.Conclusion: The study suggests that the earlier findings of improved mobility and ADL are largely driven by the positive development in higher social classes while findings of decline in SRH are related to the worsening of SRH in lower social classes.
|
|
| 13. |
- Enroth, Stefan, 1976-, et al.
(författare)
-
Data-driven analysis of a validated risk score for ovarian cancer identifies clinically distinct patterns during follow-up and treatment
- 2022
-
Ingår i: Communications Medicine. - : Springer Nature. - 2730-664X. ; 2:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundOvarian cancer is the eighth most common cancer among women and due to late detection prognosis is poor with an overall 5-year survival of 30–50%. Novel biomarkers are needed to reduce diagnostic surgery and enable detection of early-stage cancer by population screening. We have previously developed a risk score based on an 11-biomarker plasma protein assay to distinguish benign tumors (cysts) from malignant ovarian cancer in women with adnexal ovarian mass.MethodsProtein concentrations of 11 proteins were characterized in plasma from 1120 clinical samples with a custom version of the proximity extension assay. The performance of the assay was evaluated in terms of prediction accuracy based on receiver operating characteristics (ROC) and multiple hypothesis adjusted Fisher’s Exact tests on achieved sensitivity and specificity.ResultsThe assay’s performance is validated in two independent clinical cohorts with a sensitivity of 0.83/0.91 and specificity of 0.88/0.92. We also show that the risk score follows the clinical development and is reduced upon treatment, and increased with relapse and cancer progression. Data-driven modeling of the risk score patterns during a 2-year follow-up after diagnosis identifies four separate risk score trajectories linked to clinical development and survival. A Cox proportional hazard regression analysis of 5-year survival shows that at time of diagnosis the risk score is the second-strongest predictive variable for survival after tumor stage, whereas MUCIN-16 (CA-125) alone is not significantly predictive.ConclusionThe robust performance of the biomarker assay across clinical cohorts and the correlation with clinical development indicates its usefulness both in the diagnostic work-up of women with adnexal ovarian mass and for predicting their clinical course.
|
|
| 14. |
- Enroth, Stefan, 1976-
(författare)
-
Plasma Proteins and Cancer
- 2021
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:5
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The human plasma comes into contact with virtually all the cells in the human body and can be easily sampled through phlebotomy [...]
|
|
| 15. |
- Gyllensten, Ulf B., et al.
(författare)
-
Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer
- 2022
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4-7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
|
|
| 16. |
- Haycock, Philip C, et al.
(författare)
-
The association between genetically elevated polyunsaturated fatty acids and risk of cancer.
- 2023
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 91
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain.METHODS: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures.FINDINGS: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; Pheterogeneity = 0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding.INTERPRETATION: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease.
|
|
| 17. |
- Hedlund Lindberg, Julia, et al.
(författare)
-
Toward ovarian cancer screening with protein biomarkers using dried, self-sampled cervico-vaginal fluid
- 2024
-
Ingår i: iScience. - : Cell Press. - 2589-0042. ; 27:2
-
Tidskriftsartikel (refereegranskat)abstract
- Early detection is key for increased survival in ovarian cancer, but no general screening program exists today due to lack of biomarkers and overall cost versus benefit over traditional clinical methods. Here, we used dried cervico-vaginal fluid (CVF) as sampling matrix coupled with mass spectrometry for detection of protein biomarkers. We find that self-collected CVF on paper cards yields robust results and is suitable for high-throughput proteomics. Artificial intelligence–based methods were used to identify an 11-protein panel that separates cases from controls. In validation data, the panel achieved a sensitivity of 0.97 (95% CI 0.91–1.00) at a specificity of 0.67 (0.40–0.87). Analyses of samples collected prior to development of symptoms indicate that the panel is informative also of future risk of disease. Dried CVF is used in cervical cancer screening, and our results opens the possibility for a screening program also for ovarian cancer, based on self-collected CVF samples.
|
|
| 18. |
- Kierczak, Marcin, 1981-, et al.
(författare)
-
Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability
- 2022
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the success of genome-wide association studies, much of the genetic contribution to complex traits remains unexplained. Here, we analysed high coverage whole genome sequencing data, to evaluate the contribution of rare genetic variants to 414 plasma proteins. The frequency distribution of genetic variants was skewed towards the rare spectrum, and damaging variants were more often rare. We estimated that less than 4.3% of the narrow-sense heritability is expected to be explained by rare variants in our cohort. Using a gene-based approach, we identified Cis-associations for 237 of the proteins, which is slightly more compared to a GWAS (N=213), and we identified 34 loci in Trans. Several associations were driven by rare variants, and rare variants had on average larger phenotypic effects. We conclude therefore that rare variants could be of importance for precision medicine applications, but have a more limited contribution to the missing heritability of complex diseases.
|
|
| 19. |
- Kosnik, Marissa B., et al.
(författare)
-
Distinct genetic regions are associated with differential population susceptibility to chemical exposures
- 2021
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 152
-
Tidskriftsartikel (refereegranskat)abstract
- Interactions between environmental factors and genetics underlie the majority of chronic human diseases. Chemical exposures are likely an underestimated contributor, yet gene-environment (GxE) interaction studies rarely assess their modifying effects. Here, we describe a novel method to profile the human genome and identify regions associated with differential population susceptibility to chemical exposures. Single nucleotide polymorphisms (SNPs) implicated in enriched chemical-disease intersections were identified and validated for three chemical classes with expected GxE interaction potential (neuroactive, hepatoactive, and cardioactive compounds). The same approach was then used to characterize consumer product classes with unknown risk for GxE interactions (washing products, cosmetics, and adhesives). Additionally, high-risk variant sets that may confer differential population susceptibility were identified for these consumer product groups through frequent itemset mining and pathway analysis. A dataset of 2454 consumer product chemical-disease linkages, with risk values, SNPs, and pathways for each association was developed, describing the interplay between environmental factors and genetics in human disease progression. We found that genetic hotspots implicated in GxE interactions differ across chemical classes (e.g., washing products had high-risk SNPs implicated in nervous system disease) and illustrate how this approach can discover new associations (e.g., washing product n-butoxyethanol implicated SNPs in the PI3K-Akt signaling pathway for Alzheimer's disease). Hence, our approach can predict high-risk genetic regions for differential population susceptibility to chemical exposures and characterize chemical modifying factors in specific diseases. These methods show promise for describing how chemical exposures can lead to varied health outcomes in a population and for incorporating inter-individual variability into chemical risk assessment.
|
|
| 20. |
- Lara Gutiérrez, Ariadna, et al.
(författare)
-
Identification of Candidate Protein Biomarkers for CIN2+ Lesions from Self-Sampled, Dried Cervico-Vaginal Fluid Using LC-MS/MS
- 2021
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:11
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular screening programs for cervical cancer detect the presence of human papilloma virus (HPV) in cell material or vaginal fluids. Persistent infection with high-risk HPV is a necessary pre-requisite, but the majority of infections do not lead to pathological states. Additional biomarkers are needed to increase the specificity of the molecular tests. Here, we have investigated the possibility of detecting protein biomarkers using mass spectrometry from dried self-sampled cervico-vaginal fluid deposited on FTA cards. We found significant intra-individual correlations (p < 2.2 × 10-16), although heterogenous protein profiles were obtained between individuals. Out of 3699 proteins found in total, 169 were detected in at least 95% of the samples. Using a discovery/replication design, 18 proteins were found to be significant in the discovery cohort, with higher values in those cases compared to controls. All of these were found to also have higher levels among the cases in the replication cohort, with one protein (DEAD-Box Helicase) remaining statistically significant. Finally, a predictive 7-protein multivariate model was developed with a sensitivity and specificity of 0.90 and 0.55, respectively. Our results demonstrate that robust measurements of protein biomarkers can be obtained from self-sampled dried CVF and that these could be used to predict cervical cancer pre-stages.
|
|
