Association of the Bitter Taste Genes TAS2R38 and CA6 and Breast Cancer Risk; a Case-control Study of Polish Women in Poland and Polish Immigrants in USA

It is known that the perception of bitterness is mediated by type 2 bitter taste receptors (TAS2Rs). However, recent reports have suggested that the carbonic anhydrase 6 (CA6) gene may also influence bitterness sensing. Genetic variants in these genes could influence dietary intake of brassica vegetables, whose increased consumption has been observed in the literature, though inconsistently, to decrease breast cancer (BC) risk. We hypothesized that the estimated odds ratios (ORs) for the association between BC and taster diplotype (PAV/PAV) and/or genotype A/A, will be in the direction of increased BC risk, potentially due to reduced consumption of brassica vegetables. Using a case-control study of BC in Polish women in Poland (210 cases and 262 controls) and Polish immigrant women to USA (78 cases and 170 controls) we evaluated the association of the taster diplotypes in TAS2R38 gene and genotypes in the CA6 gene and BC risk in these two populations individually and jointly. No significant increase in risk was observed for the TAS2R38 PAV/PAV diplotype (tasters) in each population individually or in the joint population. For the CA6 gene, in the joint population, we observed an increased BC risk for the combined G/A and G/G genotypes (non-tasters) vs A/A (tasters), OR = 1.41 (95% CI 1.04-1.90, p = 0.026) which after adjustment for False Discovery Rate (FDR), was not significant at p≤0.05 level. However, for the joint population and for the combined genotype of the two genes AVI/AVI+G* (non-tasters) vs. PAV/*+A/A (tasters), we observed a significant increase in BC risk, OR = 1.77 (95%CI 1.47-2.74, p = 0.01), for the non-tasters, which remained significant after FDR adjustment. In conclusion for the joint population and the joint effect for the two bitter sensing genes, we observed an increase in BC risk for the bitterness non-tasters, association which is in the opposite direction to our original hypothesis.