Genetic determinants of immune-related adverse events in patients with melanoma receiving immune checkpoint inhibitors.
Adult
Aged
Aged, 80 and over
Case-Control Studies
Drug-Related Side Effects and Adverse Reactions
/ diagnosis
Female
Follow-Up Studies
Genetic Markers
Genotype
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Male
Melanoma
/ drug therapy
Middle Aged
Pilot Projects
Prognosis
Survival Rate
Young Adult
Checkpoint inhibitors
Genetics
Immune-related adverse events
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
06
05
2020
accepted:
08
11
2020
pubmed:
8
1
2021
medline:
22
6
2021
entrez:
7
1
2021
Statut:
ppublish
Résumé
Immune checkpoint inhibitors (ICIs) can cause profound immune-related adverse events (irAEs). The host genetic background is likely to play a role in irAE susceptibility because the presentation of toxicity varies among patients and many do not develop irAEs despite continued ICI use. We sought to identify potential genetic markers conferring risk for irAEs. We conducted a pilot exploratory study in 89 melanoma patients who received ICIs (44 with irAEs, and 45 without irAEs after at least 1 year from starting treatment). Genotyping was performed using the Infinium Multi-Ethnic Global-8 v1.0 Bead Chip. The genotype data were extracted using PLINK (v1.90b3.34) and processed for quality control. Population structure-based clustering was carried out using IBS matrix, pairwise population concordance test (p < 1 × 10 A total of 30 variants or single-nucleotide polymorphisms with p < 1 × 10 Several genetic variants associated with irAEs were identified. Additional larger studies are needed to validate these findings and establish their potential functional relevance.
Sections du résumé
BACKGROUND
BACKGROUND
Immune checkpoint inhibitors (ICIs) can cause profound immune-related adverse events (irAEs). The host genetic background is likely to play a role in irAE susceptibility because the presentation of toxicity varies among patients and many do not develop irAEs despite continued ICI use. We sought to identify potential genetic markers conferring risk for irAEs.
METHODS
METHODS
We conducted a pilot exploratory study in 89 melanoma patients who received ICIs (44 with irAEs, and 45 without irAEs after at least 1 year from starting treatment). Genotyping was performed using the Infinium Multi-Ethnic Global-8 v1.0 Bead Chip. The genotype data were extracted using PLINK (v1.90b3.34) and processed for quality control. Population structure-based clustering was carried out using IBS matrix, pairwise population concordance test (p < 1 × 10
RESULTS
RESULTS
A total of 30 variants or single-nucleotide polymorphisms with p < 1 × 10
CONCLUSION
CONCLUSIONS
Several genetic variants associated with irAEs were identified. Additional larger studies are needed to validate these findings and establish their potential functional relevance.
Identifiants
pubmed: 33409738
doi: 10.1007/s00262-020-02797-0
pii: 10.1007/s00262-020-02797-0
doi:
Substances chimiques
Genetic Markers
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1939-1949Subventions
Organisme : ILSI Health and Environmental Sciences Institute
ID : Thrive FP00000078
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