| 1. |
- Escala-Garcia, Maria, et al.
(författare)
-
A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
|
|
| 2. |
- Dixon-Suen, Suzanne C, et al.
(författare)
-
Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
-
Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
-
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.
|
|
| 3. |
- Kapoor, Pooja Middha, et al.
(författare)
-
Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
-
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.
|
|
| 4. |
|
|
| 5. |
- Shorter, Gillian W., et al.
(författare)
-
The "Outcome Reporting in Brief Intervention Trials: Alcohol" (ORBITAL) Core Outcome Set : International Consensus on Outcomes to Measure in Efficacy and Effectiveness Trials of Alcohol Brief Interventions
- 2021
-
Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 82:5, s. 638-646
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this study was to report the "Outcome Reporting in Brief Intervention Trials: Alcohol" (ORBITAL) recommended core outcome set (COS) to improve efficacy and effectiveness trials/evaluations for alcohol brief interventions (ABIs).Method: A systematic review identified 2,641 outcomes in 401 ABI articles measured by 1,560 different approaches. These outcomes were classified into outcome categories, and 150 participants from 19 countries participated in a two-round e-Delphi outcome prioritization exercise. This process prioritized 15 of 93 outcome categories for discussion at a consensus meeting of key stakeholders to decide the COS. A psychometric evaluation determined how to measure the outcomes.Results: Ten outcomes were voted into the COS at the consensus meeting: (a) typical frequency, (b) typical quantity, (c) frequency of heavy episodic drinking, (d) combined consumption measure summarizing alcohol use, (e) hazardous or harmful drinking (average consumption), (1) standard drinks consumed in the past week (recent, current consumption), (g) alcohol-related consequences, (h) alcohol-related injury, (i) use of emergency health care services (impact of alcohol use), and (j) quality of life.Conclusions: The ORBITAL COS is an international consensus standard for future ABI trials and evaluations. It can improve the synthesis of new findings, reduce redundant/selective reporting (i.e., reporting only some, usually significant outcomes), improve between-study comparisons, and enhance the relevance of trial and evaluation findings to decision makers. The COS is the recommended minimum and does not exclude oilier. additional outcomes.
|
|
| 6. |
- Thomson, Gill, et al.
(författare)
-
Exploring the use and experience of an infant feeding genogram to facilitate an assets-based approach to support infant feeding.
- 2020
-
Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A lack of perceived social support influences women's infant feeding behaviours. The Infant Feeding Genogram is a visual co-constructed diagram which details people/services that can provide support to women and can facilitate a connection between mothers and their existing assets landscape. The aim of this study is to explore women's and infant feeding helpers' experiences and use of an infant feeding genogram delivered to the intervention group of the "Assets-based infant feeding help Before and After birth (ABA)" randomised feasibility trial.METHODS: 103 primiparous mothers aged 16+ years were recruited to the trial (trial registration number) in two sites (Site A and Site B) with low breastfeeding prevalence in the UK. Infant feeding helpers (IFHs) co-constructed a genogram at the first antenatal meeting for the intervention group (n = 50), and then provided proactive, woman-centered support from ~ 32 weeks gestation to up to 5 months postnatal. Infant feeding helpers' and women's experiences of the infant feeding genogram were collected via interviews or focus groups. Completed genograms were shared with researchers. Content analysis of the genograms and qualitative data from the interviews and focus groups were analysed thematically.RESULTS: Data comprised 32 completed genograms, and qualitative insights from all 13 infant feeding helpers (two focus groups; 4 interviews) and interviews with a purposive sample of 21 of 50 intervention group women between 4 and 21 weeks after birth. Content analysis of the genograms highlighted variations, with more personal, individualised genograms completed at Site B compared to Site A. The perceived impact of the genogram was related to the IFHs' application of the tool. The genogram was either used as intended to raise women's awareness of available assets and motivate help-seeking behaviour, or as a data collection tool with limited perceived utility. Negative and positive unintended consequences of genogram use were highlighted.CONCLUSIONS: The genogram has the potential to offer a woman, family and community-centred approach that focusses on building assets for infant feeding. However, variations in genogram application indicate that revised training is required to clarify the purpose and ensure it is used as intended.TRIAL REGISTRATION: ISRCTN ISRCTN14760978 ; Registered 30 January 2017.
|
|
