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Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer

BACKGROUND: Genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritabilit...

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Autores principales: Barontini, Jonathan, Antinucci, Marco, Tofanelli, Sergio, Cammalleri, Maurizio, Dal Monte, Massimo, Gemignani, Federica, Vodicka, Pavel, Marangoni, Roberto, Vodickova, Ludmila, Kupcinskas, Juozas, Vymetalkova, Veronika, Forsti, Asta, Canzian, Federico, Stein, Angelika, Moreno, Victor, Mastrodonato, Nicola, Tavano, Francesca, Panza, Anna, Barale, Roberto, Landi, Stefano, Campa, Daniele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603047/
https://www.ncbi.nlm.nih.gov/pubmed/28915899
http://dx.doi.org/10.1186/s12876-017-0659-9
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author Barontini, Jonathan
Antinucci, Marco
Tofanelli, Sergio
Cammalleri, Maurizio
Dal Monte, Massimo
Gemignani, Federica
Vodicka, Pavel
Marangoni, Roberto
Vodickova, Ludmila
Kupcinskas, Juozas
Vymetalkova, Veronika
Forsti, Asta
Canzian, Federico
Stein, Angelika
Moreno, Victor
Mastrodonato, Nicola
Tavano, Francesca
Panza, Anna
Barale, Roberto
Landi, Stefano
Campa, Daniele
author_facet Barontini, Jonathan
Antinucci, Marco
Tofanelli, Sergio
Cammalleri, Maurizio
Dal Monte, Massimo
Gemignani, Federica
Vodicka, Pavel
Marangoni, Roberto
Vodickova, Ludmila
Kupcinskas, Juozas
Vymetalkova, Veronika
Forsti, Asta
Canzian, Federico
Stein, Angelika
Moreno, Victor
Mastrodonato, Nicola
Tavano, Francesca
Panza, Anna
Barale, Roberto
Landi, Stefano
Campa, Daniele
author_sort Barontini, Jonathan
collection PubMed
description BACKGROUND: Genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin. Given the importance of inflammation in CRC, we tested whether polymorphic variants in this gene could affect the risk of developing this neoplasia hypothesizing a role of TAS2R16 in modulating chronic inflammation within the gut. METHODS: We performed an association study using 6 tagging SNPs, (rs860170, rs978739, rs1357949, rs1525489, rs6466849, rs10268496) that cover all TAS2R16 genetic variability. The study was carried out on 1902 CRC cases and 1532 control individuals from four European countries. RESULTS: We did not find any statistically significant association between risk of developing CRC and selected SNPs. However, after stratification by histology (colon vs. rectum) we found that rs1525489 was associated with increased risk of rectal cancer with a (P(trend) of = 0.0071). CONCLUSIONS: Our data suggest that polymorphisms within TAS2R16 gene do not have a strong influence on colon cancer susceptibility, but a possible role in rectal cancer should be further evaluated in larger cohorts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12876-017-0659-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-56030472017-09-20 Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer Barontini, Jonathan Antinucci, Marco Tofanelli, Sergio Cammalleri, Maurizio Dal Monte, Massimo Gemignani, Federica Vodicka, Pavel Marangoni, Roberto Vodickova, Ludmila Kupcinskas, Juozas Vymetalkova, Veronika Forsti, Asta Canzian, Federico Stein, Angelika Moreno, Victor Mastrodonato, Nicola Tavano, Francesca Panza, Anna Barale, Roberto Landi, Stefano Campa, Daniele BMC Gastroenterol Research Article BACKGROUND: Genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin. Given the importance of inflammation in CRC, we tested whether polymorphic variants in this gene could affect the risk of developing this neoplasia hypothesizing a role of TAS2R16 in modulating chronic inflammation within the gut. METHODS: We performed an association study using 6 tagging SNPs, (rs860170, rs978739, rs1357949, rs1525489, rs6466849, rs10268496) that cover all TAS2R16 genetic variability. The study was carried out on 1902 CRC cases and 1532 control individuals from four European countries. RESULTS: We did not find any statistically significant association between risk of developing CRC and selected SNPs. However, after stratification by histology (colon vs. rectum) we found that rs1525489 was associated with increased risk of rectal cancer with a (P(trend) of = 0.0071). CONCLUSIONS: Our data suggest that polymorphisms within TAS2R16 gene do not have a strong influence on colon cancer susceptibility, but a possible role in rectal cancer should be further evaluated in larger cohorts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12876-017-0659-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-09-15 /pmc/articles/PMC5603047/ /pubmed/28915899 http://dx.doi.org/10.1186/s12876-017-0659-9 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Barontini, Jonathan
Antinucci, Marco
Tofanelli, Sergio
Cammalleri, Maurizio
Dal Monte, Massimo
Gemignani, Federica
Vodicka, Pavel
Marangoni, Roberto
Vodickova, Ludmila
Kupcinskas, Juozas
Vymetalkova, Veronika
Forsti, Asta
Canzian, Federico
Stein, Angelika
Moreno, Victor
Mastrodonato, Nicola
Tavano, Francesca
Panza, Anna
Barale, Roberto
Landi, Stefano
Campa, Daniele
Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer
title Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer
title_full Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer
title_fullStr Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer
title_full_unstemmed Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer
title_short Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer
title_sort association between polymorphisms of tas2r16 and susceptibility to colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603047/
https://www.ncbi.nlm.nih.gov/pubmed/28915899
http://dx.doi.org/10.1186/s12876-017-0659-9
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