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- Murphy, Neil, et al.
(författare)
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Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1300-1312.e20
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development.Methods: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls])Results: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2.Conclusions: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
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| 2. |
- Sidhu, Baldeep S., et al.
(författare)
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The effect of centre volume and procedure location on major complications and mortality from transvenous lead extraction : an ESC EHRA EORP European Lead Extraction ConTRolled ELECTRa registry subanalysis
- 2020
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 22:11, s. 1718-1728
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Tidskriftsartikel (refereegranskat)abstract
- AIMS : Transvenous lead extraction (TLE) should ideally be undertaken by experienced operators in a setting that allows urgent surgical intervention. In this analysis of the ELECTRa registry, we sought to determine whether there was a significant difference in procedure complications and mortality depending on centre volume and extraction location.METHODS AND RESULTS : Analysis of the ESC EORP European Lead Extraction ConTRolled ELECTRa registry was conducted. Low-volume (LoV) centres were defined as <30 procedures/year, and high-volume (HiV) centres as ≥30 procedures/year. Three thousand, two hundred, and forty-nine patients underwent TLE by a primary operator cardiologist; 17.1% in LoV centres and 82.9% in HiV centres. Procedures performed by primary operator cardiologists in LoV centres were less likely to be successful (93.5% vs. 97.1%; P < 0.0001) and more likely to be complicated by procedure-related deaths (1.1% vs. 0.4%; P = 0.0417). Transvenous lead extraction undertaken by primary operator cardiologists in LoV centres were associated with increased procedure-related major complications including death (odds ratio 1.858, 95% confidence interval 1.007-3.427; P = 0.0475). Transvenous lead extraction locations varied; 52.0% operating room, 9.5% hybrid theatre and 38.5% catheterization laboratory. Rates of procedure-related major complications, including death occurring in a high-risk environment (combining operating room and hybrid theatre), were similar to those undertaken in the catheterization laboratory (1.7% vs. 1.6%; P = 0.9297).CONCLUSION : Primary operator cardiologists in LoV centres are more likely to have extractions complicated by procedure-related deaths. There was no significant difference in procedure complications between different extraction settings. These findings support the need for TLE to be performed in experienced centres with appropriate personnel present.
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