Variations in the bitterness perception-related genes TAS2R38 and CA6 modify the risk for colorectal cancer in Koreans

Abstract

Bitterness perception is known to be an important factor in individuals' dietary behaviors and is also associated with the sensing of nutritious/noxious molecules for subsequent metabolic responses in multiple organs. Therefore, the genetic variation in bitterness sensing may be associated with diet-related diseases, including colorectal cancer (CRC). We investigated the influence of variations in the bitterness-sensing genes taste receptor type 2 member 38 (TAS2R38) and carbonic anhydrase 6 (CA6) on the consumption of food, tobacco and alcohol and the risk of CRC in Koreans. The study population consisted of 681 cases and 1361 controls, and their intake of vegetables, fruits, fiber, fat-food and sweets was analyzed. The genotypes for TAS2R38 A49P, V262A and I296V and CA6 rs2274333 A/G were assessed using the MassArray technique. Our findings suggested that the TAS2R38 diplotype, CA6 rs2274333 and their combined genotype had a negligible influence on dietary and alcohol intake. The combined TAS2R38-CA6 AVI/AVI-AA genotype was associated with higher tobacco consumption than the other genotypes in CRC cases only. However, the genetic variations were a significant risk factor for CRC. The TAS2R38 AVI/AVI diplotype and CA6 G allele were associated with a reduced risk of CRC. Moreover, when the combined genotypes of the subjects were analyzed, possessing both the variant diplotype/variant allele (AVI/AVI+G*) was associated with a greater reduction in the risk of CRC (adjusted OR = 0.49; 95%CI: 0.34-0.74). In summary, variations in the bitterness perception genes TAS2R38 and CA6 did not influence the examined food intake in Koreans. However, those genetic variants were a decisive modifying factor of CRC susceptibility.

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

“…Earlier studies predicted that carriers of the TAS2R38 AVI/AVI diplotype or AVI haplotype were at greater risk for cancer compared with those with the PAV/PAV diplotype (3,33). However, in Koreans, the AVI/AVI diplotype was observed not to increase the risk but rather to protect against CRC (18). Experimental evidence may explain the contrasting findings between these studies.…”

“…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).…”

“…A single study was performed in a Polynesian (native Hawaiian) population (17). Three of the studies focused on the incidence of CRC and the effect of TAS2R38 genetic variants (3,18). Another three studies investigated AP, a major antecedent of CRC (17).…”

“…Recently, an increasing number of studies have been conducted to examine whether TAS2R38 genetic variation is responsible for GI disorders, especially cancer. Researchers have reported that the AVI haplotype or AVI homo-diplotype is associated with the incidence of gastric cancer (GC) and colorectal cancer (CRC) (3,17,18). However, the association between TAS2R38 genetic variation and GI neoplasms is still controversial (3,17).…”

Genetic variations in TAS2R3 and TAS2R4 bitterness receptors modify papillary carcinoma risk and thyroid function in Korean females

“…Growing evidence suggests that T2Rs play a role in disease aetiology, with genetic variants serving as modifying factors. The association between TAS2R38 diplotype and gastrointestinal cancer has been reported in multiple ethnic groups; however, the precise underlying mechanisms are not fully understood to date 13 – 15 . A pathogenic role of the genetic variations in bitterness receptors was also evident in the exterior of alimentary systems.…”