title: HLA and Risk of Diffuse Large B cell Lymphoma After Solid Organ Transplantation.
abstract: BACKGROUND
  Solid organ transplant recipients have heightened risk for diffuse large B cell lymphoma (DLBCL). The role of donor-recipient HLA mismatch and recipient HLA type on DLBCL risk are not well established.
  
  
  METHODS
  We examined 172 231 kidney, heart, pancreas, and lung recipients transplanted in the United States between 1987 and 2010, including 902 with DLBCL. Incidence rate ratios (IRRs) were calculated using Poisson regression for DLBCL risk in relation to HLA mismatch, types, and zygosity, adjusting for sex, age, race/ethnicity, year, organ, and transplant number.
  
  
  RESULTS
  Compared with recipients who had 2 HLA-DR mismatches, those with zero or 1 mismatch had reduced DLBCL risk, (zero: IRR, 0.76, 95% confidence interval [95% CI], 0.61-0.95; one: IRR, 0.83; 95% CI, 0.69-1.00). In stratified analyses, recipients matched at either HLA-A, -B, or -DR had a significantly reduced risk of late-onset (>2 years after transplantation), but not early-onset DLBCL, and there was a trend for decreasing risk with decreasing mismatch across all 3 loci (P = 0.0003). Several individual recipient HLA-A, -B, -C, -DR, and -DQ antigens were also associated with DLBCL risk, including DR13 (IRR, 0.74; 95% CI, 0.57-0.93) and B38 (IRR, 1.48; 95% CI, 1.10-1.93), confirming prior findings that these 2 antigens are associated with risk of infection-associated cancers.
  
  
  CONCLUSIONS
  In conclusion, variation in HLA is related to susceptibility to DLBCL, perhaps reflecting intensity of immunosuppression, control of Epstein-Barr virus infection among transplant recipients or chronic immune stimulation.
authors.affiliation: 1 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA. 2 Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA. 3 Terasaki Foundation Laboratory, Los Angeles, CA. 4 Departments of Obstetrics and Gynecology and Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA. 5 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. 6 Cancer Prevention Institute of California, Fremont, CA. 7 Division of Epidemiology, Department of Health Research and Policy and Medicine, Stanford University School of Medicine, Stanford, CA. 8 Department of Epidemiology, University of Iowa, Iowa City, IA. 9 Scientific Registry of Transplant Recipients and Minneapolis Medical Research Foundation, Minneapolis, Minneapolis, MN.
authors.forename: Shehnaz K
authors.initials: SK
authors.lastname: Hussain
authors.forename: Solomon B
authors.initials: SB
authors.lastname: Makgoeng
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Everly
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
authors.forename: Christina A
authors.initials: CA
authors.lastname: Clarke
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Jon
authors.initials: J
authors.lastname: Snyder
authors.forename: Ajay
authors.initials: A
authors.lastname: Israni
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Kasiske
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
mesh_terms: D000328:Adult; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D012306:Risk
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens