CTLA-4 polymorphisms are associated with treatment outcomes of patients with multiple myeloma receiving bortezomib-based regimens.

Abstract:

:Single-nucleotide polymorphisms (SNPs) of cytotoxic T lymphocyte antigen-4 (CTLA-4) are important risk factors associated with autoimmune diseases and malignancies. This study explored the association of CTLA-4SNPs with the development of myeloma and evaluated the outcome of patients receiving bortezomib-based regimens in relation to CTLA-4SNPs. Peripheral blood samples from 86 patients with multiple myeloma (MM) and 154 healthy controls were obtained to investigate CTLA4 polymorphisms. Five SNP genotypes of CTLA-4, namely, -1772 (rs733618), -1661 (rs4553808), -318 (rs5742909), CT60 (rs3087243), and +49 (rs231775), were evaluated through TaqMan SNP genotyping assays (Applied Biosystems). Some of the CTLA-4 polymorphisms displayed frequencies that vary among ethnic groups. Kaplan-Meier analysis revealed that patients with rs733618 GG showed a significantly lower disease-free survival (0 vs. 57.4%, P = 0.020) and overall survival (46.3 vs. 83.3%, P = 0.026) than those with GA+AA following bortezomib-based therapy. Multivariate analyses showed that rs733618 GG was a risk factor for OS (HR = 0.012; 95% CI = 0.001-0.199; P = 0.002). The incidence of nonhematologic grade 3/4 adverse events significantly increased in the rs4553808 GG+GA group compared with that in the AA group (P = 0.036). CTLA-4 rs733618 GG reduced the progression-free survival and the overall survival of patients with MM who received bortezomib-based therapy. Information regarding CTLA-4 polymorphisms and haplotypes may be used to improve MM therapy. Future studies must determine the precise effect of CTLA-4 polymorphisms and haplotypes on MM therapy outcomes by using different cohorts with a large number of subjects.

journal_name

Ann Hematol

journal_title

Annals of hematology

authors

Qin XY,Lu J,Li GX,Wen L,Liu Y,Xu LP,Chang YJ,Liu KY,Jiang ZF,Huang XJ

doi

10.1007/s00277-017-3203-7

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

485-495

issue

3

eissn

0939-5555

issn

1432-0584

pii

10.1007/s00277-017-3203-7

journal_volume

97

pub_type

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