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- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 2. |
- Li, Hui-xiang, et al.
(författare)
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[Expressions of thymidine phosphorylase, thymidylate synthase and dihydropyrimidine dehydrogenase in breast cancer and their correlations with prognosis]
- 2004
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Ingår i: Zhonghua zhong liu za zhi [Chinese journal of oncology]. - Beijing, China : Zhongguo Yixue Kexueyuan / Cancer Hospital, Chinese Academy of Medical Sciences. - 0253-3766. ; 26:11, s. 669-672
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the expression of thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) mRNA in breast cancer and its correlation with prognosis.Methods: Expression levels of TP, TS and DPD mRNA in 86 micro-selected breast cancer tissues and 9 normal breast tissues were detected by real-time quantitative PCR.Results: The median expression levels of TP, TS and DPD mRNA in tumor tissue and in normal tissues were 16.54, 0.38, 2.47 and 11.75, 0.25, 8.33, respectively, there were no significant differences (P >0.05). The expression levels of TP, TS and DPD mRNA showed no association with tumor size, lymph node metastasis, pathological grade and clinical stage, except that of DPD showed a negative association with patients' ages. There was no significant difference in disease-free survival or overall survival between the patients with high and low TP or DPD mRNA levels. Disease-free survival tends to be better in the patients with low TS mRNA level than those with high TS mRNA, but the difference was not significant (P=0.069), while the overall survival showed a statistically difference (59.00 month and 70.30 month) (P=0.0496).Conclusion: The expression level of TS mRNA may serve as a prognostic marker for breast cancer patients.
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