Genotyping Analysis of Bitter-Taste Receptor Genes <i>TAS2R38</i> and <i>TAS2R46</i> in Japanese Patients with Gastrointestinal Cancers

Abstract

Summary Type-2 bitter-taste receptors (TAS2Rs) are important for the evaluation of food quality and the nutritional control in animals. Mutations in some TAS2Rs including TAS2R38 are known to increase susceptibility to various diseases. However, the involvement of TAS2Rs in cancers has not been well understood. We conducted a pilot study by genotyping two TAS2R genes, TAS2R38 and TAS2R46, in Japanese cancer patients diagnosed with the following types of cancer: biliary tract cancer, hepatocellular carcinoma, pancreatic cancer, colorectal cancer and gastric cancer. We selected the two TAS2Rs because they carry virtually non-functional alleles in human populations. We found that cancer risk is not associated with any TAS2R46 genotypes since there were no significant differences in genotype frequencies between cancer patients and controls. On the other hand, we confirmed that phenylthiocarbamide (PTC) non-tasters homozygous (AVI/AVI) for TAS2R38 were more frequent among Japanese cancer patients than those among controls as suggested in a previous study. The AVI/AVI genotype was therefore considered to increases cancer risk. In contrast, we also found that homozygous (PAV/PAV) PTC tasters are less frequent among cancer patients, suggesting that the PAV/PAV is a cancer resistant genotype that decreases cancer risk. Genotype frequencies for heterozygous AVI/PAV genotype were not significantly different between the two groups. It is suggested that the risk and resistance of cancers is antagonistically controlled by the two TAS2R38 alleles, PAV and AVI, rather than by the AVI allele alone.

TAS2R38 Bitterness Receptor Genetic Variation and Risk of Gastrointestinal Neoplasm: A Meta-Analysis

“…Epidemiological studies in multiple ethnicities were conducted to examine the association between the T2R38 bitterness receptor and cancer with genetic variation as a modifying factor. Increased risk for colorectal and GI cancer associated with the TAS2R38 AVI/AVI diplotype was observed in Germans and Japanese (3,20). A Korean study also showed that PAV/AVI increased the risk for GC (19).…”

“…The studies were all designed for case-control investigations. Specifically, three and four studies were conducted in Caucasian (3,17) and Asian populations (17)(18)(19)(20), respectively. A single study was performed in a Polynesian (native Hawaiian) population (17).…”

“…One study by Choi et al reported the influence of TAS2R38 genetic variants on GC (19). Yamaki's Japanese study reported the association between the TAS2R38 diplotype and GI cancer (20). However, the study was not stratified by neoplasm type because the number of cases for each cancer type was limited [e.g., GC (n ¼ 18) or CRC (n ¼ 21)].…”

Expression of Bitter Taste Receptors in the Intestinal Cells of Non-Human Primates

“…RNAseq failed to detect other TAS2Rs. Of note, TAS2R38 expression in the intestine is related to the risk of intestinal cancers associated with the taster/non-taster phenotype [10]. To confirm the expression pattern of TAS2R38 in the intestine, we performed RT-qPCR analyses of TAS2R38, GNAT3 (gustducin), and TRPM5 (Tables S2, S3 and Figure 2).…”

A Study of the Relationship between the Taste Sensitivity of Phenylthiocarbamide (PTC) and Blood Pressure (Random Sample from the Students of Qurna College/Basrah-Iraq)

“…It has been found that non-tasters of PTC is more confused in the accuracy of taste compared to the tasters and this may lead to the infection of some diseases at sometimes [38]. Also, both alleles of the taster or non-taster of the PTC can contribute to the infection and the resistance of some diseases being the non-taster are the most susceptible [39] [40]. Timpson et al [21] pointed to the possibility of non-taster infected by heart disease and stroke more than tasters, but the results did not confirm this.…”