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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Analysis of 12 variants in the development of gastric and colorectal cancers
Giovanna C Cavalcante, Marcos AT Amador, André M Ribeiro dos Santos, Darlen C Carvalho, Roberta B Andrade, Esdras EB Pereira, Marianne R Fernandes, Danielle F Costa, Ney PC Santos, Paulo P Assumpção, Ândrea Ribeiro dos Santos, Sidney Santos
Giovanna C Cavalcante, Marcos AT Amador, André M Ribeiro dos Santos, Darlen C Carvalho, Roberta B Andrade, Ney PC Santos, Ândrea Ribeiro dos Santos, Sidney Santos, Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
Giovanna C Cavalcante, Darlen C Carvalho, Roberta B Andrade, Esdras EB Pereira, Marianne R Fernandes, Danielle F Costa, Ney PC Santos, Paulo P Assumpção, Ândrea Ribeiro dos Santos, Sidney Santos, Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
Author contributions: Cavalcante GC and Amador MAT performed the laboratory experiments; Cavalcante GC, Carvalho DC and Andrade RB drafted the manuscript; Pereira EEB, Fernandes MR and Costa DF provided the samples for the study; Cavalcante GC, Ribeiro dos Santos AM and Santos S performed the data analysis; Santos S reviewed the statistical methods of the study; Santos NPC, Assumpção PP and Ribeiro dos Santos  made substantial contributions to the study design and the manuscript; Cavalcante GC and Santos S designed the study and wrote the final version of the paper.
Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Pró-Reitoria de Pesquisa e Pós-Graduação da Universidade Federal do Pará/Fundação Amparo e Desenvolvimento da Pesquisa (PROPESP-UFPA/FADESP).
Institutional review board statement: The study was approved by the Committee for Research Ethics of the Hospital João de Barros Barreto under Protocol No. CAAE 25865714.6.0000.0017.
Informed consent statement: All participants provided their informed consent prior to study inclusion.
Conflict-of-interest statement: The authors declare no conflict of interests in this study.
Data sharing statement: No additional data are available.
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: Sidney Santos, PhD, Professor, Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Rua Augusto Correa 01, Belém 66075-970, Brazil.
sidneysantos@ufpa.br
Telephone: +55-91-32017843 Fax: +55-91-32017843
Received: September 14, 2017
Peer-review started: September 15, 2017
First decision: October 10, 2017
Revised: October 25, 2017
Accepted: November 8, 2017
Article in press: November 8, 2017
Published online: December 28, 2017
Processing time: 103 Days and 20.7 Hours
AIM
To evaluate the relation between 12 polymorphisms and the development of gastric cancer (GC) and colorectal cancer (CRC).
METHODS
In this study, we included 125 individuals with GC diagnosis, 66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms (in CASP8, CYP2E1, CYP19A1, IL1A, IL4, MDM2, NFKB1, PAR1, TP53, TYMS, UGT1A1 and XRCC1 genes) were genotyped in a single PCR for each individual, followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 ancestry-informative markers that can also be genotyped by multiplex PCR. The statistical analyses were performed in Structure v.2.3.4, R environment and SPSS v.20.
RESULTS
After statistical analyses with the control of confounding factors, such as genetic ancestry, three markers (rs79071878 in IL4, rs3730485 in MDM2 and rs28362491 in NFKB1) were positively associated with the development of GC. One of these markers (rs28362491) and the marker in the UGT1A1 gene (rs8175347) were positively associated with the development of CRC. Therefore, we investigated whether the joint presence of the deleterious alleles of each marker could affect the development of cancer and we obtained positive results in all analyses. Carriers of the combination of alleles RP1 + DEL (rs79071878 and rs28361491, respectively) are at 10-times greater risk of developing GC than carriers of other combinations. Similarly, carriers of the combination of DEL + RARE (rs283628 and rs8175347) are at about 12-times greater risk of developing CRC than carriers of other combinations.
CONCLUSION
These findings are important for the comprehension of gastric and CRC development, particularly in highly admixed populations, such as the Brazilian population.
Core tip: Gastric cancer and colorectal cancer (CRC) are among the most incident and aggressive types of cancer in Brazil, especially in the Amazon region. Alterations in genes involved in pathways of immune responses, inflammatory processes or genomic and cellular stability may generate cellular imbalances and lead to tumorigenesis. Therefore, it is vital to understand the effect of different alleles in the development of gastric and CRC, which could contribute to the early detection of these types of cancer, increasing the survival chances of the patient.
