TAS2R38 polymorphisms, Helicobacter pylori infection and susceptibility to gastric cancer and premalignant gastric lesions

Eur J Cancer Prev. 2022 Sep 1;31(5):401-407. doi: 10.1097/CEJ.0000000000000722. Epub 2021 Oct 11.

Abstract

Background: Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori , and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population.

Methods: We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer.

Results: Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 ( P = 0.006) and rs1726866 ( P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04-2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80-2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction.

Conclusion: In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology.

MeSH terms

  • Genotype
  • Helicobacter Infections* / complications
  • Helicobacter Infections* / genetics
  • Helicobacter pylori / physiology
  • Humans
  • Precancerous Conditions* / genetics
  • Receptors, G-Protein-Coupled / genetics*
  • Stomach Neoplasms* / etiology
  • Stomach Neoplasms* / genetics

Substances

  • Receptors, G-Protein-Coupled
  • taste receptors, type 2