Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer

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.Electronic supplementary materialThe online version of this article (10.1186/s12876-017-0659-9) contains supplementary material, which is available to authorized users.

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“…Its incidence and mortality rates increase annually and are even rising among younger age groups. 1 , 2 Based on the latest statistics, it is expected that in 2020, the number of new CRC cases in the United States will reach 147,950, and the number of deaths will exceed 53,200. 3 The continuous development of painless colonoscopy, targeted therapy and immunotherapy has greatly promoted the development of early screening, diagnosis and treatment of CRC, 4 , 5 yet CRC, as a kind of molecular heterogeneous disease, is intractable Some studies have shown that the 5-year survival rate of CRC is about 32.8% - 61.4%.…”

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions

“…Further, genome-wide association studies (GWAS) have identified numerous genetic loci that are associated with CRC, but hereditability remains unknown. More than 40 low-penetrant polymorphic variants are reported [ 25 ]. More recently in a Finnish cohort, a single-nucleotide polymorphism (SNP) rs992157 at chromosome 2q35 intronic to PNKD and TMBIMI was found to be associated with CRC [ 26 ].…”

T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma

“…T2Rs have also been explored in some cancers [14][15][16][17][18][19][20][21][22][23], including thyroid [22], salivary [23], and GI cancers [14][15][16][17][18][19]. Polymorphisms in the TA2R38 gene encoding the T2R38 receptor are associated with elevated cancer risk [16][17][18]24].…”