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- Bornelöv, Susanne, et al.
(författare)
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Rule-Based Models of the Interplay between Genetic and Environmental Factors in Childhood Allergy
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e80080-
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Tidskriftsartikel (refereegranskat)abstract
- Both genetic and environmental factors are important for the development of allergic diseases. However, a detailed understanding of how such factors act together is lacking. To elucidate the interplay between genetic and environmental factors in allergic diseases, we used a novel bioinformatics approach that combines feature selection and machine learning. In two materials, PARSIFAL (a European cross-sectional study of 3113 children) and BAMSE (a Swedish birth-cohort including 2033 children), genetic variants as well as environmental and lifestyle factors were evaluated for their contribution to allergic phenotypes. Monte Carlo feature selection and rule based models were used to identify and rank rules describing how combinations of genetic and environmental factors affect the risk of allergic diseases. Novel interactions between genes were suggested and replicated, such as between ORMDL3 and RORA, where certain genotype combinations gave odds ratios for current asthma of 2.1 (95% CI 1.2-3.6) and 3.2 (95% CI 2.0-5.0) in the BAMSE and PARSIFAL children, respectively. Several combinations of environmental factors appeared to be important for the development of allergic disease in children. For example, use of baby formula and antibiotics early in life was associated with an odds ratio of 7.4 (95% CI 4.5-12.0) of developing asthma. Furthermore, genetic variants together with environmental factors seemed to play a role for allergic diseases, such as the use of antibiotics early in life and COL29A1 variants for asthma, and farm living and NPSR1 variants for allergic eczema. Overall, combinations of environmental and life style factors appeared more frequently in the models than combinations solely involving genes. In conclusion, a new bioinformatics approach is described for analyzing complex data, including extensive genetic and environmental information. Interactions identified with this approach could provide useful hints for further in-depth studies of etiological mechanisms and may also strengthen the basis for risk assessment and prevention.
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| 2. |
- Rojvall, Annika Svanstrom, et al.
(författare)
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Impact of radiotherapy on bone health in women with rectal cancer- A prospective cohort study
- 2022
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Ingår i: European Journal of Surgical Oncology. - : ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 48:12, s. 2509-2517
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Pelvic radiotherapy (RT) increases the risk of pelvic insufficiency fractures. The aim was to investigate if RT is associated with changes in serum bone biomarkers in women with rectal cancer, and to examine the incidence of radiation-induced bone injuries and the association with bone biomarkers.Material and methods: Women diagnosed with rectal cancer stage I-III, planned for abdominal surgery +/- preoperative (chemo) RT, were prospectively included and followed one year. Serum bone biomarkers comprised sclerostin (regulatory of bone formation), CTX (resorption), BALP and PINP (for-mation). A subgroup was investigated with annual pelvic magnetic resonance imaging (MRI). The as-sociation between RT and bone biomarkers was explored in regression models.Results: Of 134 included women, 104 had surgery with preoperative RT. The formation markers BALP and PINP increased from baseline to one year in the RT-exposed group (p < 0.001, longitudinal comparison). In the adjusted regression analysis, the mean increase in PINP was higher in the RT-exposed than the unexposed group (17.6 (3.6-31.5) mg/L, p = 0.013). Sclerostin and CTX did not change within groups nor differed between groups. Radiation-induced injuries were detected in 16 (42%) of 38 women with available MRI. At one year, BALP was higher among women with than without bone injuries (p = 0.018, cross-sectional comparison).Conclusions: Preoperative RT was associated with an increase in the formation marker PINP, which could represent bone recovery following RT-induced injuries, commonly observed in participants evaluated with MRI. These findings should be further explored in larger prospective studies on bone health in rectal cancer patients.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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