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

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.