Double-edged sword of inflammasome genetics in colorectal cancer prognosis

Raylane Adrielle Gonçalves Cambui; Gilmar Ferreira do Espírito Santo; Fernanda Pereira Fernandes; Vinicius Nunes Cordeiro Leal; Bianca Borsatto Galera; Emerson Giuliano Palacio Fávaro; Leonardo Amorim Rizzo; Rosa Maria Elias; Alessandra Pontillo

doi:10.1016/j.clim.2020.108373

Double-edged sword of inflammasome genetics in colorectal cancer prognosis

Clin Immunol. 2020 Apr:213:108373. doi: 10.1016/j.clim.2020.108373. Epub 2020 Mar 2.

Authors

Raylane Adrielle Gonçalves Cambui¹, Gilmar Ferreira do Espírito Santo², Fernanda Pereira Fernandes³, Vinicius Nunes Cordeiro Leal³, Bianca Borsatto Galera⁴, Emerson Giuliano Palacio Fávaro⁵, Leonardo Amorim Rizzo⁶, Rosa Maria Elias⁶, Alessandra Pontillo³

Affiliations

¹ Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil; Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: raylanecambui@gmail.com.
² Instituto de Tumores e Cuidados Paliativos de Cuiabá do Hospital Geral e Maternidade de Cuiabá, Cuiabá, MT, Brazil.
³ Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
⁴ Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil.
⁵ Universidade de Cuiabá, Cuiabá, MT, Brazil.
⁶ Centro Universitário de Várzea Grande, Várzea Grande, MT, Brazil.

PMID: 32135277
DOI: 10.1016/j.clim.2020.108373

Abstract

Inflammation is a colorectal cancer (CRC) hallmark. Inflammasome-dependent cytokines IL-1ß and IL-18 can play a beneficial or detrimental role in tumorigenesis depending on cancer type. Variants in inflammasome genes were associated with tumor development and/or outcome, and have been proposed as potential biomarkers for population screening. In this study, 215 CRC patients followed-up for 10 years were examined for 9 polymorphisms in selected inflammasome genes. Multivariate association analysis and survival analysis were performed to evaluate the association between the polymorphisms and CRC prognosis. Variants associated with lower levels of IL-18 (rs1834481, rs5744256), or with increased activation of inflammasome receptors NLRP1 (rs12150220) and NLRP3 (rs35829419) resulted detrimental to CRC prognosis and may be used as prognostic markers.

Keywords: Colorectal cancer; IL18; Inflammasome; NLRP1; NLRP3; SNPs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / immunology
Adult
Aged
Aged, 80 and over
Apoptosis Regulatory Proteins / genetics*
Apoptosis Regulatory Proteins / immunology
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / immunology
Colorectal Neoplasms / pathology
Female
Genetic Predisposition to Disease / genetics
Humans
Inflammasomes / genetics*
Inflammasomes / immunology
Interleukin-18 / genetics*
Interleukin-18 / immunology
Male
Middle Aged
NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
NLR Family, Pyrin Domain-Containing 3 Protein / immunology
NLR Proteins
Polymorphism, Single Nucleotide
Prognosis
Young Adult

Substances

Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
IL18 protein, human
Inflammasomes
Interleukin-18
NLR Family, Pyrin Domain-Containing 3 Protein
NLR Proteins
NLRP1 protein, human
NLRP3 protein, human