Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer

Jonathan Barontini,Roberto Marangoni,Massimo Dal Monte,Sergio Tofanelli,Marco Antinucci,Angelika Stein,Roberto Barale,Anna Panza,Federico Canzian,Maurizio Cammalleri,Stefano Landi,Federica Gemignani,Nicola Mastrodonato,Francesca Tavano,Juozas Kupčinskas ,Asta Försti ,Ľudmila Vodičková ,Vı́ctor Moreno ,Veronika Vymetalková ,Pavel Vodička ,Daniele Campa

doi:10.1186/s12876-017-0659-9

Abstract

BackgroundGenetics 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.MethodsWe 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.ResultsWe 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 (Ptrend of = 0.0071).ConclusionsOur 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.

Highlights

Genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC)
In this study we focused our attention on the genetic variability of the TAS2R16 gene whose encoded receptor selectively binds to salicin [32], a natural anti-inflammatory and analgesic agent extracted from willow bark and resembling aspirin [33]
Data filtering and quality control We examined 6 Single nucleotide polymorphism (SNP) belonging to the TAS2R16 gene to assess their possible role in the risk of developing CRC

Summary

Introduction

Genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). 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. There are evidences from case-control and cohort studies indicating benefit from long term use of aspirin at low dose in colorectal cancer chemoprevention [34]. This effect could be elicited through an anti-inflammatory activity or to the binding to specific receptors in the gut. The study was carried out in a large cohort of European individuals

Methods

Results

Discussion

Conclusion