LIM domain only 2 protein expression,LMO2germline genetic variation, and overall survival in diffuse large B-cell lymphoma in the pre-rituximab era
Year: 2011
Type: article
Study design: Observational Study
Abstract: Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] = 0.55; 95% confidence interval [CI] 0.31-0.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p = 0.02). Compared to a model with clinical factors only (c-statistic = 0.676), adding the four SNPs (c-statistic = 0.751) or LMO2 IHC (c-statistic = 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic = 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.
Authors: James R. Cerhan, Yasodha Natkunam, Lindsay M. Morton, Matthew J. Maurer, Yan Asmann, Thomas M. Habermann, Mohammad A. Vasef, Wendy Cozen, Charles F. Lynch, Cristine Allmer, Susan L. Slager, Izidore S. Lossos, Stephen J. Chanock, Nathaniel Rothman, Patricia Hartge, Ahmet Dogan, Sophia S. Wang
Institutions: Mayo Clinic, Stanford Medicine, Stanford University, Division of Cancer Epidemiology and Genetics, University of New Mexico, University of Southern California, University of Iowa, University of Miami, University of Miami Health System, City Of Hope National Medical Center, City of Hope
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: UNRESOLVED PUBLIC HEALTH ISSUES RELATED TO HT AND CANCER, G1499445388, SURVEILLANCE EPIDEMIOLOGY &END RESULTS PROGRAM, G1788914148, SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS--SEER, G1932976417, G2111860640, #14: Residual Tissue Repository to Create HIV Cancer Tumor Tissue Microrarrays , SURVEILLANCE EPIDEMIOLOGY &END RESULTS PROGRAM, G2652134439, G2660289629, G3120360579, G420411562, Immunogenetics of Non-Hodgkin Lymphoma Survival, G4836174358, G490749545, G5185757912, G5372537626, G578395707, G7278087418, G7752797991, University of Southern California Norris Comprehensive Cancer Center Support Grant (CCSG)
OpenAlex ID: W2108989128