| 11. |
- Tian, Yu, et al.
(author)
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Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
- 2024
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In: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130:10, s. 1687-1696
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Journal article (peer-reviewed)abstract
- Background: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.Methods: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.Results: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10−8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%–4.0%) vs 6.1% (5.7%–6.5%) (difference 2.4%, P-value = 1.83 × 10−14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%–1.8%) vs 2.2% (1.9%–2.4%) (difference 0.6%, P-value = 1.01 × 10−3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.Conclusions: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
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| 12. |
- Tian, Yu, et al.
(author)
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Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk
- 2022
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In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:8, s. 1135-1148
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Journal article (peer-reviewed)abstract
- BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
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| 13. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 14. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 15. |
- Brainin, Michael, et al.
(author)
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Poststroke chronic disease management: towards improved identification and interventions for poststroke spasticity-related complications.
- 2011
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In: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 6:1, s. 42-6
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Journal article (peer-reviewed)abstract
- This paper represents the opinion of a group of researchers and clinicians with an established interest in poststroke care and is based on the recognised need for long-term care following stroke, especially in view of the global increase of disability due to stroke. Among the more frequent long-term complications following stroke are spasticity-related disabilities. Although spasticity alone occurs in up to 60% of stroke survivors, disabling spasticity affects only 4-10%. Spasticity further interferes with important functions of daily life when it occurs in association with pain, motor impairment, and overall declines of cognitive and neurological function. It is proposed that the aftermath of stroke be considered a chronic disease requiring a multifactorial and multilevel approach. There are, however, knowledge gaps related to the prediction and recognition of poststroke disability. Interventions to prevent or minimise such disabilities require further development and evaluation. Poststroke spasticity research should focus on reducing disability and be considered as part of a continuum of chronic care requirements and should be recognised as a part of a comprehensive poststroke disease management programme.
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| 16. |
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| 17. |
- D'Humières, Benoit, et al.
(author)
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The C3PO project : A laser communication system concept for small satellites
- 2017
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9781510606333
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Conference paper (peer-reviewed)abstract
- The satellite market is shifting towards smaller (micro and nanosatellites), lowered mass and increased performance platforms. Nanosatellites and picosatellites have been used for a number of new, innovative and unique payloads and missions. This trend requires new concepts for a reduced size, a better performance/weight ratio and a reduction of onboard power consumption. In this context, disruptive technologies, such as laser-optical communication systems, are opening new possibilities. This paper presents the C3PO1 system, "advanced Concept for laser uplink/ downlink CommuniCation with sPace Objects", and the first results of the development of its key technologies. This project targets the design of a communications system that uses a ground-based laser to illuminate a satellite, and a Modulating Retro-Reflector (MRR) to return a beam of light modulated by data to the ground. This enables a downlink, without a laser source on the satellite. This architecture suits well to small satellite applications so as high data rates are potentially provided with very low board mass. C3PO project aims to achieve data rates of 1Gbit/s between LEO satellites and Earth with a communication payload mass of less than 1kilogram. In this paper, results of the initial experiments and demonstration of the key technologies will be shown.
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| 18. |
- Drew, David A., et al.
(author)
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Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer
- 2024
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:22
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Journal article (peer-reviewed)abstract
- Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
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| 19. |
- Duncan, Duane, et al.
(author)
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Making gender along the way : women, men and harm in Australian alcohol policy
- 2022
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In: Critical Policy Studies. - : Informa UK Limited. - 1946-0171 .- 1946-018X. ; 16:1, s. 1-18
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Journal article (peer-reviewed)abstract
- Analysis of alcohol policy suggests women are marked out for special attention while men and masculinities are often ignored. In this paper, we employ Carol Bacchi’s work on ‘gendering practices’ and John Law’s concept of ‘collateral realities’ to examine how gender is constituted in Australian alcohol policy. For Bacchi, policies actively produce what it is possible for ‘men’ and ‘women’ to become. For Law, realities are constituted through methodological instruments and representational practices. We analyze the making of three collateral realities in Australian alcohol policy: gender as an individual attribute; gender as a synonym for women; and gender as confined to the domestic sphere. These collateral realities contribute to the maintenance of binary notions of gender and reinforce a straightforwardly causal role for alcohol in harms, including violence. Attention to the political effects of these ‘realities’ should be prioritized in the development of more equitable responses to alcohol and harm.
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| 20. |
- Duncan, Duane, et al.
(author)
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The hammer and the nail : The triple lock of methods, realities and institutional contexts in Australian research on nightlife violence
- 2022
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In: International journal of drug policy. - : Elsevier BV. - 0955-3959 .- 1873-4758. ; 110
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Journal article (peer-reviewed)abstract
- There is considerable public and policy debate in Australia about measures to reduce violence associated with alcohol and young people in the night-time economy. Though overrepresented in violence, the role of men and masculinities is rarely explicitly addressed in policy responses to such violence, which rest on a narrow range of mainly quantitative research and recommendations favouring blanket alcohol restrictions. Drawing on John Law and colleagues’ account of the ‘double social life of methods’ (2011), we analyse interviews conducted with Australian quantitative researchers about the role of gender in such violence. According to Law et al., methods inhabit and reproduce particular ecologies and reflect the concerns of those who advocate them. From this ‘triple lock’ of methods, realities, and institutional advocacies and contexts emerges particular modes of knowing. Participants described a research ecology in which the authority of quantitative research methods emerged in relation to an imperative to respond in a ‘timely’ and ‘pragmatic’ fashion to public policy debates, and prevailing governmental and policy priorities and public framings of violence. Though participants frequently acknowledged the role of men in violence, these arrangements sustain taken-for-granted assumptions about the properties and effects of alcohol while displacing men and masculinities from policy attention. The political consequences of these arrangements demand the development of innovative policy responses and new modes of knowing that make visible the gendering of violence.
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