Genotyping Analysis of Bitter-Taste Receptor Genes TAS2R38 and TAS2R46 in Japanese Patients with Gastrointestinal Cancers
Genotyping Analysis of Bitter-Taste Receptor Genes TAS2R38 and TAS2R46 in Japanese Patients with Gastrointestinal Cancers
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DOI：
10.3177/jnsv.63.148
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发表时间：
2017-04-01
影响因子：
1.6
通讯作者：
Komai, Michio
中科院分区：
文献类型：
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作者：
Yamaki, Michiko;Saito, Hiroki;Komai, Michio
2型苦味受体(TAS2Rs)在动物的食物质量评价和营养调控中具有重要意义。已知包括TAS2R38在内的一些TAS2R的突变会增加对各种疾病的易感性。然而，TAS2Rs在癌症中的作用还不是很清楚。我们通过对患有胆道癌、肝细胞癌、胰腺癌、结直肠癌和胃癌的日本癌症患者的两个TAS2R基因TAS2R38和TAS2R46进行了一项初步研究。我们选择了两个TAS2R，因为它们在人类群体中携带几乎不起作用的等位基因。我们发现癌症风险与任何TAS2R46基因类型无关，因为癌症患者和对照组之间的基因频率没有显著差异。另一方面，我们证实了TAS2R38的苯硫脲(PTC)非品尝者纯合子(AVI/AVI)在日本癌症患者中比先前研究中建议的对照组中更常见。因此，AVI/AVI基因型被认为会增加癌症风险。相反，我们还发现纯合子(PAV/PAV)PTC品尝者在癌症患者中较少出现，这表明PAV/PAV是一种降低癌症风险的抗癌基因。AVI/PAV杂合型基因频率在两组间差异无统计学意义。提示肿瘤的风险和耐药性是由两个TAS2R38等位基因PAV和AVI拮抗控制的，而不是仅由AVI等位基因控制。
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.