Contributions
Abstract: PB2123
Type: Publication Only
Background
Programmed cell death-1 (PD-1), PD-1 ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays an important role in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PDCD1, PDL1 and CTLA4 have been reported to be associated with susceptibility to some cancers. However, the potential association between SNPs in these immune checkpoint genes and risk of multiple myeloma (MM) remain controversial and obscure.
Aims
The aims of this study were to clarify the influence of PDCD1, PDL1 and CTLA4 SNPs on the risk of developing MM and its clinical features.
Methods
We extracted the genomic DNA from 125 MM patients and 211 healthy controls, and determined 3 PDCD1 SNPs (rs36084323, rs41386349, rs2227982), 2 PDL1 SNPs (rs2297136, rs4143815) and 4 CTLA4 (rs733618, rs1157131, rs231775, rs3087243) by using the PCR-restriction fragment length polymorphism or the TaqMan allelic discrimination real-time PCR method. Haplotypes were statistically inferred from PDCD1, PDL1 and CTLA4 genotype data using Haploview version 4.2 (www.broad.mit.edu/mpg/haploview). All statistical analyses were performed with the IBM SPSS software package ver. 24 (IBM, Armonk, NY, USA). This study was approved by the Institutional Review Board of Gunma University Hospital (Approval #160007).
Results
The patients with MM had a significantly higher frequency of the PDCD1 GCC/GCC haplotype (rs36084323 high-expression type/rs41386349 high-expression type/rs2227982) compared with healthy controls (10.4% vs. 4.3%, OR = 2.61, p = 0.028). However, no statistically significant differences were observed in the genotype and the haplotype of PDL1 and CTLA4 SNPs between MM patients and healthy controls. In MM patients, the PDCD1 rs41386349 CT & TT genotypes (low-expression type) was associated with significantly higher frequency of patients with plasmacytoma at diagnosis than the CC genotype (high-expression type) (30.4% vs. 14.5%, p = 0.039). The PDCD1 rs2227982 CC genotype was associated with significantly higher frequency of patients with bone lesion than the CT & TT genotypes (86.0% vs. 68.3%, p = 0.033). Moreover, the PDL1 rs2297136 TT & TC genotypes (high expression type) was associated with significantly lower albumin level than the CC genotype (low expression type) (mean±SD 3.84±0.65 vs. 4.36±0.54, p = 0.038). The CTLA4 rs733618 AG & GG genotypes (low-expression type) was associated with significantly higher frequency of patients with plasmacytoma at diagnosis than the AA genotype (high-expression type) (27.0% vs. 9.8%, p = 0.029). In addition, the CTLA4 rs1157131 GG genotype had a higher frequency of patients with ISS stage III than the AA & AG genotypes (43.8% vs. 26.2%, p = 0.040). However, we observed no significant difference in OS of MM patients among PDCD1, PDL1 and CTLA4 SNPs.
Conclusion
Our findings indicate that PDCD1 polymorphisms may contribute to susceptibility of MM. The polymorphisms in immune checkpoint gene is not associated with the prognosis of MM but PDCD1, PDL1 and CTLA4 SNPs may be associated with extra-medullary disease and severity of MM.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): CTLA-4, Multiple Myeloma, SNP
Abstract: PB2123
Type: Publication Only
Background
Programmed cell death-1 (PD-1), PD-1 ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays an important role in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PDCD1, PDL1 and CTLA4 have been reported to be associated with susceptibility to some cancers. However, the potential association between SNPs in these immune checkpoint genes and risk of multiple myeloma (MM) remain controversial and obscure.
Aims
The aims of this study were to clarify the influence of PDCD1, PDL1 and CTLA4 SNPs on the risk of developing MM and its clinical features.
Methods
We extracted the genomic DNA from 125 MM patients and 211 healthy controls, and determined 3 PDCD1 SNPs (rs36084323, rs41386349, rs2227982), 2 PDL1 SNPs (rs2297136, rs4143815) and 4 CTLA4 (rs733618, rs1157131, rs231775, rs3087243) by using the PCR-restriction fragment length polymorphism or the TaqMan allelic discrimination real-time PCR method. Haplotypes were statistically inferred from PDCD1, PDL1 and CTLA4 genotype data using Haploview version 4.2 (www.broad.mit.edu/mpg/haploview). All statistical analyses were performed with the IBM SPSS software package ver. 24 (IBM, Armonk, NY, USA). This study was approved by the Institutional Review Board of Gunma University Hospital (Approval #160007).
Results
The patients with MM had a significantly higher frequency of the PDCD1 GCC/GCC haplotype (rs36084323 high-expression type/rs41386349 high-expression type/rs2227982) compared with healthy controls (10.4% vs. 4.3%, OR = 2.61, p = 0.028). However, no statistically significant differences were observed in the genotype and the haplotype of PDL1 and CTLA4 SNPs between MM patients and healthy controls. In MM patients, the PDCD1 rs41386349 CT & TT genotypes (low-expression type) was associated with significantly higher frequency of patients with plasmacytoma at diagnosis than the CC genotype (high-expression type) (30.4% vs. 14.5%, p = 0.039). The PDCD1 rs2227982 CC genotype was associated with significantly higher frequency of patients with bone lesion than the CT & TT genotypes (86.0% vs. 68.3%, p = 0.033). Moreover, the PDL1 rs2297136 TT & TC genotypes (high expression type) was associated with significantly lower albumin level than the CC genotype (low expression type) (mean±SD 3.84±0.65 vs. 4.36±0.54, p = 0.038). The CTLA4 rs733618 AG & GG genotypes (low-expression type) was associated with significantly higher frequency of patients with plasmacytoma at diagnosis than the AA genotype (high-expression type) (27.0% vs. 9.8%, p = 0.029). In addition, the CTLA4 rs1157131 GG genotype had a higher frequency of patients with ISS stage III than the AA & AG genotypes (43.8% vs. 26.2%, p = 0.040). However, we observed no significant difference in OS of MM patients among PDCD1, PDL1 and CTLA4 SNPs.
Conclusion
Our findings indicate that PDCD1 polymorphisms may contribute to susceptibility of MM. The polymorphisms in immune checkpoint gene is not associated with the prognosis of MM but PDCD1, PDL1 and CTLA4 SNPs may be associated with extra-medullary disease and severity of MM.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): CTLA-4, Multiple Myeloma, SNP