| 1. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 2. |
- Dixon-Suen, Suzanne C, et al.
(författare)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 3. |
- Fottrell, Edward F, 1980-
(författare)
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Dying to count : mortality surveillance methods in resource-poor settings
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Mortality data are critical to understanding and monitoring changes in population health status over time. Nevertheless, the majority of people living in the world’s poorest countries, where the burden of disease is highest, remain outside any kind of systematic health surveillance. This lack of routine registration of vital events, such as births and deaths, constitutes a major and longstanding constraint on the understanding of patterns of health and disease and the effectiveness of interventions. Localised sentinel demographic and health surveillance strategies are a useful surrogate for more widespread surveillance in such settings, but rigorous, evidence-based methodologies for sample-based surveillance are weak and by no means standardised. This thesis aims to describe, evaluate and refine methodological approaches to mortality measurement in resource-poor settings. Methods Through close collaboration with existing community surveillance operations in a range of settings, this work uses existing data from demographic surveillance sites and community-based surveys using various innovative approaches in order to evaluate and refine methodological approaches to mortality measurement and cause-of-death determination. In doing so, this work explores the application of innovative techniques and procedures for mortality surveillance in relation to the differing needs of those who use mortality data, ranging from global health organisations to local health planners. Results Empirical modelling of sampling procedures in community-based surveys in rural Africa and of random errors in longitudinal data collection sheds light on the effects of various data-capture and quality-control procedures and demonstrates the representativeness and robustness of population surveillance datasets. The development, application and refinement of a probabilistic approach to determining causes of death at the population level in developing countries has shown promise in overcoming the longstanding limitations and issues of standardisation of existing methods. Further adaptation and application of this approach to measure maternal deaths has also been successful. Application of international guidelines on humanitarian crisis detection to mortality surveillance in Ethiopia demonstrates that simple procedures can and, from an ethical perspective, should be applied to sentinel surveillance methods for the prospective detection of important mortality changes in vulnerable populations. Conclusion Mortality surveillance in sentinel surveillance systems in resource-poor settings is a valuable and worthwhile task. This work contributes to the understanding of the effects of different methods of surveillance and demonstrates that, ultimately, the choice of methods for collecting data, assuring data quality and determining causes of death depends on the specific needs and requirements of end users. Surveillance systems have the potential to contribute substantially to developing health care systems in resource-poor countries and should not only be considered as research-oriented enterprises.
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| 4. |
- Haafkens, Joke, et al.
(författare)
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Training needs for research in health inequities among health and demographic researchers from eight African and Asian countries
- 2014
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To support equity focussed public health policy in low and middle income countries, more evidence and analysis of the social determinants of health inequalities is needed. This requires specific know how among researchers. The INDEPTH Training and Research Centres of Excellence (INTREC) collaboration will develop and provide training on the social determinants of health approach for health researchers from the International Network for the Demographic Evaluation of Populations and Their Health in Low- and Middle-Income Countries (INDEPTH) in Africa and Asia. To identify learning needs among the potential target group, this qualitative study explored what INDEPTH researchers from Ghana, Tanzania, South Africa, Kenya, Indonesia, India, Vietnam, and Bangladesh feel that they want to learn to be able to conduct research on the causes of health inequalities in their country.METHODS: Using an inductive method, online concept-mapping, participants were asked to generate statements in response to the question what background knowledge they would need to conduct research on the causes of health inequalities in their country, to sort those statements into thematic groups, and to rate them in terms of how important it would be for the INTREC program to offer instruction on each of the statements. Statistical techniques were used to structure statements into a thematic cluster map and average importance ratings of statements/clusters were calculated.RESULTS: Of the 150 invited researchers, 82 participated in the study; 54 from Africa; 28 from Asia. Participants generated 59 statements and sorted them into 6 broader thematic clusters: "assessing health inequalities"; "research design and methods"; "research and policy"; "demography and health inequalities"; "social determinants of health" and "interventions". African participants assigned the highest importance to further training on methods for assessing health inequalities. Asian participants assigned the highest importance to training on research and policy.CONCLUSION: The identified thematic clusters and statements provide a detailed understanding of what INDEPTH researchers want to learn in order to be able to conduct research on the social determinants of health inequalities. This offers a framework for developing capacity building programs in this emerging field of public health research.
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| 5. |
- Henschke, Nicholas, et al.
(författare)
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Strengthening capacity to research the social determinants of health in low-and middle-income countries : lessons from the INTREC programme
- 2017
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: The INDEPTH Training & Research Centres of Excellence (INTREC) collaboration developed a training programme to strengthen social determinants of health (SDH) research in low-and middle-income countries (LMICs). It was piloted among health-and demographic researchers from 9 countries in Africa and Asia. The programme followed a blended learning approach and was split into three consecutive teaching blocks over a 12month period: 1) an online course of 7 video lectures and assignments on the theory of SDH research; 2) a 2-week qualitative and quantitative methods workshop; and 3) a 1-week data analysis workshop. This report aims to summarise the student evaluations of the pilot and to suggest key lessons for future approaches to strengthen SDH research capacity in LMICs. Methods: Semi-structured interviews and questionnaires with 24 students from 9 countries in Africa and Asia were used to evaluate each teaching block. Information was collected about the students' motivation and interest in studying SDH, any challenges they faced during the consecutive teaching blocks, and suggestions they had for future courses on SDH. Results: Of the 24 students who began the programme, 13 (54%) completed all training activities. The students recognised the need for such a course and its potential to improve their skills as health researchers. The main challenges with the online course were time management, prior knowledge and skills required to participate in the course, and the need to get feedback from teaching staff throughout the learning process. All students found the face-to-face workshops to be of high quality and value for their work, because they offered an opportunity to clarify SDH concepts taught during the online course and to gain practical research skills. After the final teaching block, students felt they had improved their data analysis skills and were better able to develop research proposals, scientific manuscripts, and policy briefs. Conclusions: The INTREC programme has trained a promising cadre of health researchers who live and work in LMICs, which is an essential component of efforts to identify and reduce national and local level health inequities. Time management and technological issues were the greatest challenges, which can inform future attempts to strengthen research capacity on SDH.
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| 6. |
- Hofman, Karen, et al.
(författare)
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Addressing research capacity for health equity and the social determinants of health in three African countries : the INTREC programme
- 2013
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Ingår i: Global Health Action. - : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 6, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The importance of tackling economic, social and health-related inequities is increasingly accepted as a core concern for the post-Millennium Development Goal framework. However, there is a global dearth of high-quality, policy-relevant and actionable data on inequities within populations, which means that development solutions seldom focus on the people who need them most. INTREC (INDEPTH Training and Research Centres of Excellence) was established with this concern in mind. It aims to provide training for researchers from the INDEPTH network on associations between health inequities, the social determinants of health (SDH), and health outcomes, and on presenting their findings in a usable form to policy makers.OBJECTIVE: As part of a baseline situation analysis for INTREC, this paper assesses the current status of SDH training in three of the African INTREC countries - Ghana, Tanzania, and South Africa - as well as the gaps, barriers, and opportunities for training.METHODS: SDH-related courses from the three countries were identified through personal knowledge of the researchers, supplemented by snowballing and online searches. Interviews were also conducted with, among others, academics engaged in SDH and public health training in order to provide context and complementary material. Information regarding access to the Internet, as a possible INTREC teaching medium, was gathered in each country through online searches.RESULTS: SDH-relevant training is available, but 1) the number of places available for students is limited; 2) the training tends to be public-health-oriented rather than inclusive of the broader, multi-sectoral issues associated with SDH; and 3) insufficient funding places limitations on both students and on the training institutions themselves, thereby affecting participation and quality. We also identified rapidly expanding Internet connectivity in all three countries, which opens up opportunities for e-learning on SDH, though the current quality of the Internet services remains mixed.CONCLUSIONS: SDH training is currently in short supply, and there is a clear role for INTREC to contribute to the training of a critical mass of African researchers on the topic. This work will be accomplished most effectively by building on pre-existing networks, institutions, and methods.
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| 7. |
- Jung, Audrey Y, et al.
(författare)
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Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes : pooled analysis of population-based studies
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:12, s. 1706-1719
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.METHODS: Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative) and by invasiveness. All statistical tests were 2-sided.RESULTS: Compared to nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46; for multiparous women with luminal A-like tumors 20-<25 years after last birth and 45-<50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95%CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95%CI = 0.79 to 1.34, for multiparous women 25 to < 30 years after last birth). Older age at first birth (P-heterogeneity<.001 for triple-negative compared to luminal-A like) and breastfeeding (P-heterogeneity<.001 for triple-negative compared to luminal-A like) were associated with lower risk of triple-negative but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.CONCLUSION: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.
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| 8. |
- Kapoor, Pooja Middha, et al.
(författare)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 9. |
- Lindblad, Anna, et al.
(författare)
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The Incidence of Intestinal Gastric Cancer among Resettlers in Germany - Do Resettlers Remain at an Elevated Risk in Comparison to the General Population?
- 2020
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 17:24
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that the incidence of gastric cancer (GC), and particularly intestinal GC, is higher among resettlers from the former Soviet Union (FSU) than in the general German population. Our aim was to investigate if the higher risk remains over time.GC cases between 1994 and 2013, in a cohort of 32,972 resettlers, were identified by the respective federal cancer registry. Age-standardized rates (ASRs) and standardized incidence ratios (SIRs) were analyzed in comparison to the general population for GC subtypes according to the Laurén classification. Additionally, the cohort was pooled with data from a second resettler cohort from Saarland to investigate time trends using negative binomial regression.The incidence of intestinal GC was elevated among resettlers in comparison to the general population (SIR (men) 1.64, 95% CI: 1.09-2.37; SIR (women) 1.91, 95% CI: 1.15-2.98). The analysis with the pooled data confirmed an elevated SIR, which was stable over time.Resettlers' higher risk of developing intestinal GC does not attenuate towards the incidence in the general German population. Dietary and lifestyle patterns might amplify the risk of GC, and we believe that further investigation of risk behaviors is needed to better understand the development of disease pattern among migrants.
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| 10. |
- Middha, Pooja K., et al.
(författare)
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A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
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Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
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