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- Liu, Yanhong, et al.
(författare)
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Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival
- 2010
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 28:14, s. 2467-2474
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment. PATIENTS AND METHODS: Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; or= 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs. RESULTS: We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients >or= 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years). CONCLUSION: Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival.
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| 2. |
- Ljung, Lotta, et al.
(författare)
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Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis in a geographically distant National Register-based cohort : an external validation
- 2018
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Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Cardiovascular (CV) risk stratification for patients with rheumatoid arthritis (RA) should facilitate evidence-based management. Prior work has derived an internally validated a CV risk score, the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA), using US data. The aim of this study was to perform an external validation among unselected patients with RA from Europe. Methods Three large, partially overlapping, cohorts of patients with RA from the Swedish Rheumatology Quality register were identified for external validation, two with information on smoking and two with close to 10 years of median follow-up. The 10-year rate of first CV events was assessed using the Kaplan-Meier method. The performance of ERS-RA was assessed using C-index and comparisons of observed versus predicted risks. Results The C-index for ERS-RA varied across the three RA cohorts, from 0.75 to 0.78. Predicted risks corresponded well to observed risks among individuals with <= 10 % observed 10-year CV risk, but underestimated risk in individuals with a higher observed risk. In the absence of data on smoking, ERS-RA underestimated the CV risk by 3.3%, whereas in the cohorts including data on smoking, the calibration was within 1% (0.06% and 0.7%). In the clinically relevant risk intervals (<5%, 5.0%-<7.5%, 7.5%-<10%), ERS-RA performed well. Conclusions In an unselected Swedish population with RA, ERS-RA performed well, although the 10-year CV risk was underestimated in high-risk groups and in the absence of data on smoking. ERS-RA could be considered as a risk stratification tool for targeted preventive interventions in clinical rheumatology practice.
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| 4. |
- Scheurer, Michael E, et al.
(författare)
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Familial aggregation of glioma : a pooled analysis
- 2010
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:10, s. 1099-1107
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Tidskriftsartikel (refereegranskat)abstract
- In genome-wide association studies, inherited risk of glioma has been demonstrated for rare familial syndromes and with common variants from 3-5 chromosomal regions. To assess the degree of familial aggregation of glioma, the authors performed a pooled analysis of data from 2 large glioma case-control studies in the United States (MD Anderson Cancer Center, Houston, Texas (1994-2006) and University of California, San Francisco (1991-2004)) and from the Swedish Cancer Registry (1958-2006) to measure excess cases of cancer among first-degree relatives of glioma probands. This analysis included 20,377 probands with glioma and 52,714 first-degree relatives. No overall increase was found in the expected number of cancers among family members; however, there were 77% more gliomas than expected. There were also significantly more sarcoma and melanoma cases than expected, which is supported by evidence in the literature, whereas there were significantly fewer-than-expected cases of leukemia, non-Hodgkin lymphoma, and bladder, lung, pancreatic, prostate, and uterine cancers. This large pooled analysis provided sufficient numbers of related family members to examine the genetic mechanisms involved in the aggregation of glioma with other cancers in these families. However, misclassification due to unvalidated cancers among family members could account for the differences seen by study site.
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