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- Cheng, THT, et al.
(author)
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Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- 2015
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 17369-
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Journal article (peer-reviewed)abstract
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
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- Hosking, C, et al.
(author)
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Low central venous oxygen saturation in haemodynamically stabilized trauma patients is associated with poor outcome.
- 2011
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 55, s. 713-721
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Journal article (peer-reviewed)abstract
- Background: Central venous oxygen saturation (ScvO(2) ) is suggested to reflect the adequacy of oxygen delivery, and the main objective of the present study was to determine whether ScvO(2) is associated with outcome in haemodynamically stabilized trauma patients. Methods: Haemodynamically unstable trauma patients receiving a central venous line within 1 h of admission were eligible for inclusion in this prospective observational study. The mean arterial pressure (MAP), lactate and ScvO(2) were recorded at inclusion and every 6 h for 36 h or until lactate was <2.0 mmol/l and ScvO(2) was >75% in two consecutive measurements. Patients with a MAP of ≥70 mmHg were considered to be haemodynamically stabilized. The outcome measure was complications defined as infections, delta sequential organ failure assessment score of >0, and mortality. Results: Fifty patients with a median new injury severity score of 27 (17-34) were analysed. Complications occurred in 33 patients. An association between ScvO(2) following resuscitation to MAP ≥70 mmHg and complications was detected with an odds ratio of 0.94 (95% confidence interval; 0.89-0.99). This association was also significant when adjusted for injury severity. The result implies that a low ScvO(2) value is associated with more complications. The optimal cut-off for ScvO(2) to discriminate between patients who did or did not develop complications was found to be 66.5% (56-86%). Conclusions: These data suggest that low ScvO(2) in haemodynamically stabilized patients is associated with a poor outcome and that ScvO(2) represents a potential endpoint of resuscitation in trauma patients.
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- Shete, Sanjay, et al.
(author)
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Genome-wide high-density SNP linkage search for glioma susceptibility loci : results from the gliogene consortium
- 2011
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 71:24, s. 7568-7575
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Journal article (peer-reviewed)abstract
- Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. Cancer Res; 71(24); 7568-75. (C) 2011 AACR.
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