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- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 2. |
- Van Slingerland, Krista J, et al.
(författare)
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Canadian Centre for Mental Health and Sport (CCMHS) Position Statement : Principles of Mental Health in Competitive and High-Performance Sport.
- 2019
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Ingår i: Clinical Journal of Sports Medicine. - : Wolters Kluwer. - 1050-642X .- 1536-3724. ; 29:3, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- The brave decision made by many Canadian athletes to share their experience with mental illness has fed a growing dialogue surrounding mental health in competitive and high-performance sport. To affect real change for individuals, sport culture must change to meet demands for psychologically safe, supportive, and accepting sport environments. This position statement addresses mental health in competitive and high-performance sport in Canada, presenting solutions to current challenges and laying a foundation for a unified address of mental health by the Canadian sport community. The paper emerged from the first phase of a multidisciplinary Participatory Action Research (PAR) project, in which a sport-focused mental health care model housed within the Canadian Centre for Mental Health and Sport (CCMHS) is currently being designed, implemented, and evaluated by a team of 20 stakeholders, in collaboration with several community partners and advisors.
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