Yamaki Michiko, Saito Hiroki, Isono Kunio, Goto Tomoko, Shirakawa Hitoshi, Shoji Noriaki, Satoh-Kuriwada Shizuko, Sasano Takashi, Okada Ryo, Kudoh Katsuyoshi, Motoi Fuyuhiko, Unno Michiaki, Komai Michio
Department of Science of Food Function and Health, Division of Bioscience and Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University.
Department of Oral Medicine and Surgery, Division of Oral Diagnosis, Tohoku University Graduate School of Dentistry.
J Nutr Sci Vitaminol (Tokyo). 2017;63(2):148-154. doi: 10.3177/jnsv.63.148.
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.
2型苦味受体（TAS2Rs）对于动物评估食物质量和营养控制非常重要。已知包括TAS2R38在内的一些TAS2Rs发生突变会增加对各种疾病的易感性。然而，TAS2Rs在癌症中的作用尚未得到充分了解。我们对诊断患有以下类型癌症的日本癌症患者的两个TAS2R基因TAS2R38和TAS2R46进行基因分型，开展了一项初步研究：胆管癌、肝细胞癌、胰腺癌、结直肠癌和胃癌。我们选择这两个TAS2Rs是因为它们在人群中携带几乎无功能的等位基因。我们发现癌症风险与任何TAS2R46基因型均无关联，因为癌症患者和对照组之间的基因型频率没有显著差异。另一方面，正如之前一项研究所暗示的，我们证实，日本癌症患者中TAS2R38的纯合苯硫脲（PTC）味盲者（AVI/AVI）比对照组更为常见。因此，AVI/AVI基因型被认为会增加癌症风险。相比之下，我们还发现癌症患者中纯合（PAV/PAV）PTC尝味者较少，这表明PAV/PAV是一种降低癌症风险的抗癌基因型。两组之间杂合AVI/PAV基因型的频率没有显著差异。提示癌症的风险和抗性是由TAS2R38的两个等位基因PAV和AVI拮抗控制的，而不是仅由AVI等位基因控制。
