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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features
Diego Marques, Layse Raynara Ferreira-Costa, Lorenna Larissa Ferreira-Costa, Romualdo da Silva Correa, Aline Maciel Pinheiro Borges, Fernanda Ribeiro Ito, Carlos Cesar de Oliveira Ramos, Raul Hernandes Bortolin, André Ducati Luchessi, Ândrea Ribeiro-dos-Santos, Sidney Santos, Vivian Nogueira Silbiger
Diego Marques, Layse Raynara Ferreira-Costa, Lorenna Larissa Ferreira-Costa, Raul Hernandes Bortolin, André Ducati Luchessi, Vivian Nogueira Silbiger, Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
Diego Marques, Raul Hernandes Bortolin, André Ducati Luchessi, Vivian Nogueira Silbiger, Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
Diego Marques, Ândrea Ribeiro-dos-Santos, Sidney Santos, Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66055-080, Pará, Brazil
Romualdo da Silva Correa, Aline Maciel Pinheiro Borges, Fernanda Ribeiro Ito, Departamento de Cirurgia Oncológica, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
Carlos Cesar de Oliveira Ramos, Laboratório de Patologia e Citopatologia, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
André Ducati Luchessi, Vivian Nogueira Silbiger, Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
Ândrea Ribeiro-dos-Santos, Sidney Santos, Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Pará, Brazil
Author contributions: Ribeiro-dos-Santos A, Santos S and Silbiger VN designed the research; Correa RS, Borges AMP and Ito FR selected patients and collected clinical data; Ramos CCO collected histopathological data; Marques D, Ferreira-Costa LR and Ferreira-Costa LL collected biological material and performed the assays; Marques D, Bortolin RH and Luchessi AD analyzed the data; Marques D wrote the paper; Bortolin RH, Silbiger VN and Ribeiro-dos-Santos A critically revised the manuscript; Silbiger VN approved final version of the article to be published.
Supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), No. 483031/2013-5; Rede de Pesquisa em Genomica Populacional Humana, No. Biocomputacional/CAPES-051/2013; Fundação de Amparo à Pesquisa do Estado do Pará, No. 155/2014; and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Norte, No. 005/2011.
Institutional review board statement: This study was reviewed and approved by the Liga Norte Riograndense Contra o Câncer Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at viviansilbiger@hotmail.com; viviansilbiger@ufrnet.br.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vivian Nogueira Silbiger, PhD, Professor, Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Rio Grande do Norte, Av. General Gustavo Cordeiro de Faria S/N, Petrópolis, Natal 59012-570, Rio Grande do Norte, Brazil. viviansilbiger@ufrnet.br
Telephone: +55-84-33429807 Fax: +55-84-33429833
Received: April 17, 2017
Peer-review started: April 27, 2017
First decision: June 5, 2017
Revised: June 24, 2017
Accepted: August 15, 2017
Article in press: August 15, 2017
Published online: October 7, 2017
AIM
To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population.
METHODS
One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients’ clinical charts, intra-operative documentation, and pathology scoring.
RESULTS
Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE, HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk.
CONCLUSION
The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.
Core tip: The insertion-deletions (INDEL) variations in IL4 gene was associated with increased colorectal cancer (CRC) risk, while TYMS and UP2 genes were associated with decreased risk. The Del-alleles of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. The Ins-alleles of ACE, HLAG and TP53 were associated with higher TNM stage. The Ins-allele of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del-allele of TYMS. The Ins-alleles of SGSM3 and UGT1A1 were associated with death risk. These data suggest that these INDEL might be useful as a complementary tool for better CRC clinical management.
