ArticleCancer chemotherapy and pharmacology2025
Association of IL12RB2, RORC, and class II HLA polymorphisms with severe erythema multiforme of regorafenib in Japanese patients with colorectal cancer.
Article in Cancer chemotherapy and pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeThe anticancer drug regorafenib can induce erythema multiforme (EM), an immune-mediated cutaneous and mucosal hypersensitivity reaction. We prospectively analyzed regorafenib in patients with metastatic colorectal cancer (mCRC) and found that seven of 40 patients had grade 3 EM, which resulted in treatment discontinuation. In this study, we retrospectively examined genetic polymorphisms associated with regorafenib-induced severe EM.
methodsTo identify associated polymorphisms, exploratory whole-exome sequencing was performed focusing on factors related to type IV hypersensitivity reaction in seven patients each, with and without grade 3 EM. The identified EM-related polymorphisms were analyzed in all 40 patients. Class II human leukocyte antigen (HLA) typing was also performed for all patients.
resultsThe frequency of interleukin 12 receptor (IL12R)B2 rs2229546 A/A was higher in patients with grade 3 EM than in those without it (P = 0.00622, Pc = 0.0622 [Bonferroni corrections]). Polymorphisms of the retinoic acid receptor-related orphan receptor (ROR)C, rs2280471 G, rs12145375 T, rs12144914 G, and rs55841824 T comprised haplotype I. The frequency of patients homozygous or heterozygous for haplotype I was lower in those with grade 3 EM than in those without EM (P = 0.0108, Pc = 0.108). The combination of the risk genotype of IL12RB2 rs2229546 A/A and the risk diplotype that did not contain RORC haplotype I was significantly associated with a higher incidence of grade 3 EM (P = 0.000383, Pc = 0.00153). The class II HLA haplotypes were not associated with EM.
conclusionsType IV hypersensitivity reaction-related polymorphisms were associated with regorafenib-induced EM. TRIAL REGISTRATION NUMBER AND DATE: UMIN000013939, registered on May 12, 2014, when six months after approval by the Institutional Review Board of Showa Medical University.
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