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- Machiela, Mitchell J, et al.
(författare)
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Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:5, s. 747-754
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.
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| 103. |
- Muller, D. C., et al.
(författare)
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No association between circulating concentrations of vitamin D and risk of lung cancer : an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3)
- 2018
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 29:6, s. 1468-1475
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3).Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables.Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology.Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.
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| 110. |
- Nordenstedt, H, et al.
(författare)
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The relation between gastroesophageal reflux and respiratory symptoms in a population-based study : the Nord-Tröndelag health survey
- 2006
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Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 129:4, s. 1051-1056
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Tidskriftsartikel (refereegranskat)abstract
- Background In spite of numerous investigations, the relation between respiratory symptoms and reflux symptoms in the general population remains unclear, since population-based studies are few. Study objectives To investigate the relation between respiratory symptoms and reflux symptoms in the population. Subject and methods In a cohort of 65,363 individuals representing 71.2% of the adult population in the Norwegian county of Nord-Trøndelag, 58,596 individuals (89.6%) responded to questions concerning reflux symptoms. The 3,153 persons (5.4%) with severe and recurrent reflux symptoms constituted the case group, and the 40,210 persons (68.6%) without reflux symptoms served as the control group. Odds ratios (ORs) with 95% confidence intervals (CIs) represented relative risks. Potential confounding was tested in multivariable logistic regression analysis. Results Persons with asthma had reflux to a 60% greater extent than those without asthma after including adjustment for asthma medication (OR, 1.6; 95% CI, 1.4 to 1.9). There was a statistically significant dose-response association between breathlessness and reflux symptoms (p for trend < 0.0001), and the OR of severe breathlessness was 12.0 (95% CI, 9.5 to 15.2). Persons with heavy and wheezy breathing, daily cough, daily productive cough, or chronic cough showed a twofold to threefold statistically significant increase in risk of reflux symptoms. Adjustment for asthma or use of asthma medication did not substantially influence the risk estimates for any of the studied respiratory disorders. Conclusions Reflux symptoms commonly coexist with asthma and other respiratory symptoms on a population-based level, seemingly irrespective of asthma medication.
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