Genetic susceptibility to diffuse large B-cell lymphoma in a pooled study of three Eastern Asian populations

Bryan A. Bassig, James R. Cerhan, Wing Yan Au, Hee Nam Kim, Suleeporn Sangrajrang, Wei Hu, Jovic Tse, Sonja Berndt, Tongzhang Zheng, Heping Zhang, Pattarapong Pornsopone, Je Jung Lee, Hyeoung Joon Kim, Christine F. Skibola, Joseph Vijai, Laurie Burdette, Meredith Yeager, Paul Brennan, Min Ho Shin, Raymond LiangStephen Chanock, Qing Lan, Nathaniel Rothman

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide. The first large-scale genome-wide association study (GWAS) of DLBCL with over 4000 cases conducted among individuals of European ancestry recently identified five independent SNPs that achieved genome-wide significance, and two SNPs that showed a suggestive association with DLBCL risk. Methods: To evaluate whether Eastern Asians and individuals of European ancestry share similar genetic risk factors for this disease, we attempted to replicate these GWAS findings in a pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea, and Thailand. Results: Three of the five genome-wide significant SNPs from the DLBCL GWAS were significantly associated with DLBCL in our study population, including the top finding from the GWAS, EXOC2 rs116446171, which achieved genome-wide significance in our data (per allele OR = 2.04, 95% CI = 1.63-2.56; ptrend = 3.9 × 10-10). Additionally, we observed a significant association with PVT1 rs13255292 (per allele OR = 1.34, 95% CI = 1.19-1.52; ptrend = 2.1 × 10-6), which was the second strongest finding in the GWAS, and with HLA-B rs2523607 (per allele OR = 3.05, 95% CI = 1.32-7.05; ptrend = 0.009). Conclusions: Our study, which provides the first evaluation in Eastern Asians of SNPs definitively associated with DLBCL risk in individuals of European ancestry, indicates that at least some of the genetic factors associated with risk of DLBCL are similar between these populations.

Original languageEnglish (US)
Pages (from-to)442-448
Number of pages7
JournalEuropean Journal of Haematology
Volume95
Issue number5
DOIs
StatePublished - Nov 2015

Keywords

  • Diffuse large B-cell lymphoma
  • Eastern asians
  • Genetic susceptibility to DLBCL
  • Lymphoma

ASJC Scopus subject areas

  • Hematology

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