Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

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BACKGROUND: Single nucleotide polymorphisms (SNPs) of cancer-immunity relevant genes may decide the extent of tumor immunosurveillance and have clinical significance. The Immuno ALCL trial was designed to investigate whether genetic variability in 13 cancer-immunity relevant genes correlated with clinical features and outcome of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) patients. METHODS: One hundred eighty patients were enrolled and genotyped for 14 SNPs. Age at diagnosis, progression-free survival, histological subtype and anti-ALK antibody titer data were collected. RESULTS: IL10 rs1800872, IL10 rs1800896 and TLR3 rs3775291 variants significantly correlated with age at diagnosis. TLR3 rs3775291 was associated with progression-free survival in a recessive model. Combination of multiple genetic variations showed a trend to associate with post-therapeutic relapse. None of the SNP analyzed associated with histological or clinical parameters. CONCLUSION: Despite the low number of patients, our work uncovered potential associations between certain cancer-immunity relevant genes and clinical features of ALK-positive ALCL patients. Associations do not imply causations. However, our work highlighted a possible contribution of the IL10 and TLR3 pathways to ALK-positive ALCL pathogenesis and suggested that several genetic variants in concert may modulate the risk of post-therapeutic relapse. TRIAL REGISTRATION: clinicaltrial.gov NCT02902874. Registered 07 September 2016 https//clinicaltrials.gov/study/NCT02902874.

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