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- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 2. |
- Lutz, Barbara S., et al.
(författare)
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Role of the target in end-to-side neurorrhaphy : reinnervation of a single muscle vs. multiple muscles
- 2000
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Ingår i: Journal of reconstructive microsurgery. - : Georg Thieme Verlag KG. - 0743-684X .- 1098-8947. ; 16:6, s. 443-448
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Tidskriftsartikel (refereegranskat)abstract
- The authors examined the effects of end-to-side neurorrhaphy for reinnervation of the musculocutaneous nerve (Group A) which innervates the biceps muscle, compared to reinnervation of the median nerve which innervates multiple muscles in a rat model. Additionally, end-to-end neurorrhaphy to the musculocutaneous nerve using one-third of the median nerve (Group B) was investigated. End-to-end coaptation of the musculocutaneous nerve served as a control (Group C). In a grooming test, the biceps muscle function in Group A animals demonstrated a slower but nearly similar good recovery to Groups B and C. Biceps muscle contraction force investigated after 24 weeks demonstrated no statistically significant differences among all groups. In Groups A and B, no significant impairment of the donor median nerve function was found in a grasping test and the muscle contraction force of the flexor carpi radialis muscle, and histologic evaluation of the musculocutaneous nerve showed multiple regenerated axons distal to the coaptation site. Retrograde double-labeling in Group A animals showed reinnervation of the musculocutaneous nerve by median nerve axons located at the coaptation site. These results validate that end-to-side neurorrhaphy to a nerve innervating a single muscle is more efficient than to a nerve innervating multiple muscles, as demonstrated in an earlier study. The reason for this phenomenon is most likely that all sprouting axons are directed toward one target rather than toward multiple targets, with the latter situation resulting in a smaller number of axons and a variable distribution of axons per target. Since donor nerve sprouting axons were observed at the coaptation site, a relevance of the selected site for end-to-side neurorrhaphy is suggested. Both end-to-side neurorrhaphy and end-to-end neurorrhaphy, using one-third of the median nerve, led to useful functional recovery in this rat model, if an agonistic donor nerve is employed.
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| 3. |
- Lutz, Barbara S., et al.
(författare)
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Selection of donor nerves : an important factor in end-to-side neurorrhaphy
- 2000
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Ingår i: British Journal of Plastic Surgery. - : Elsevier BV. - 0007-1226 .- 1465-3087. ; 53:2, s. 149-154
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the effects of end-to-side neurorrhaphy on peripheral nerve regeneration usingthe median nerve as recipient nerve and either the antagonistic radial nerve or the agonistic ulnar nerve as donor nerves in rat upper limbs. A perineural window was created in all cases. Motor recovery up to 16 weeks postoperation was tested with the grasping test. No recovery of motor function was evident after end-to-side neurorrhaphy of the median nerve to the antagonistic radial nerve, whereas six of eight rats with end-to-side neurorrhaphy to the agonistic ulnar nerve achieved 367 g±47 g grasping power as compared to 526 g±6 g in end-to-end coapted control animals. No significant difference in flexor digitorum sublimus-motor nerve conduction velocity was found among all three groups. Radial nerve stimulation produced simultaneous contraction of both extensor and flexor muscles of the lower arm that disabled any coordinated movement of the paw. Histology (toluidine blue, acetylcholinesterase-stain) showed multiple regenerated (motor)-axons distal to the coaptation site in the median nerve. Reinnervation of the median nerve solely by the respective donor nerve was demonstrated by a retrograde double labelling technique. These results show that averaged 70% muscle power as compared to end-to-end neurorrhaphy with well coordinated muscle function can be achieved by axonal sprouting through end-to-side neurorrhaphy if an agonistic nerve is used as donor nerve. However, satisfying results are unpredictable. Antagonistic nerves show the ability to induce axonal regeneration, but no useful function can be expected.
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