Citations 2
Elevated Urine LeukotrieneE4Is Associated With Worse Objective Markers in Nasal Polyposis Patients
O’Brien, Erin K. , Smith, Alyssa J. , Barnes, Jason H. , Stokken, Janalee K., Strumpf, Andrew , Divekar, Rohit , Stokken, Janalee K. , Choby, Garret , Smith, Alyssa , Barnes, Jason , Hagan, John, O'Brien, Erin K , Carlson, Matthew L , Choby, Garret , Hagan, John, Mattos, José L. , Payne, Spencer C.
The Laryngoscope | October 1, 2020 | Volume: 131 | Issue: 5 | Pages: 961-966
ObjectivesUrine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin‐exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin‐tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP.MethodsA retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund‐Mackay CT score, spirometry and lab values) were collected.ResultsAmong the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P< .001), aspirin sensitivity (P< .001), worse Lund‐Mackay CT scores (P= .002) and other objective markers of disease severity including serum IgE (P= .05), presenting blood eosinophil level (P< .001), and the highest recorded eosinophil level (P< .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (Rrange 0.31–0.52) than the aspirin tolerant CRSwNP group (Rrange −0.30–0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores).ConclusionElevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient‐reported symptom measures.Level of Evidence3Laryngoscope, 131:961–966, 2021
Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer
Roberts, Nicholas J. , Norris, Alexis L. , Petersen, Gloria M. , Bondy, Melissa L. , Gallinger, Steven , Kurtz, Robert C. , Olson, Sara H. , Rustgi, Anil K. , Schwartz, Ann G. , Zogopoulos, George , Ali, Syed Z. , Axilbund, Jennifer E., Chaffee, Kari G. , Childs, Erica J., Herman, Joseph M. , Kramer, Melissa , Makohon-Moore, Alvin P. , McCombie, W. Richard , McMahon, K. Wyatt, Niknafs, Noushin , Parla, Jennifer, Pirooznia, Mehdi , Potash, James B. , Rhim, Andrew D. , Smith, Alyssa , Wolfgang, Christopher L. , Wood, Laura D. , Zandi, Peter P. , Karchin, Rachel , Eshleman, James R. , Papadopoulos, Nickolas , Kinzler, Kenneth W. , Vogelstein, Bert , Hruban, Ralph H. , Rabe, Kari G. , Brand, Randall E. , Stoffel, Elena M. , Syngal, Sapna , Chen, Yunching , Coté, Michele L. , Douville, Christopher , Goes, Fernando , Iacobuzio–Donahue, Christine A. , Wang, Yuxuan , Goggins, Michael , Klein, Alison P. , Pirooznia, Mehdi
Cancer Discovery | December 9, 2015 | Volume: 6 | Issue: 2 | Pages: 166-175
Abstract Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genomes of 638 patients with familial pancreatic cancer and the tumor exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A, and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identification of susceptibility genes in other common cancer types. Significance: The genetic basis of disease susceptibility in the majority of patients with familial pancreatic cancer is unknown. We whole genome sequenced 638 patients with familial pancreatic cancer and demonstrate that the genetic underpinning of inherited pancreatic cancer is highly heterogeneous. This has significant implications for the management of patients with familial pancreatic cancer. Cancer Discov; 6(2); 166–75. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 109