Association of 758 G/A polymorphism of 3'untranslated region of prohibitin with risk of gastric cancer

Background: A polymorphic variant allele (T-allele) in the 3'-UTR of prohibitin (C-to-T at nucleotide 729) was reported to be associated with an increased risk of breast cancer. However, the association between the 3'-UTR polymorphism of prohibitin and the susceptibility to gastric cancer remains unknown. Thus, we investigated the distribution of prohibitin genotypes in Chinese patients with gastric cancer and subsequently analyzed the association between the 3'-UTR polymorphism of prohibitin and the risk of gastric cancer in that population.

Methods: The distribution of 3'-UTR polymorphism of prohibitin in 82 gastric cancer patients was determined by sequencing and compared with that of 171 healthy controls. Luciferase reporter assay was used to investigate the effect of 3'-UTRs variant on PHB expression.

Results: Our study discovered two major polymorphic sites in the 3'-UTR of prohibitin (C-to-T at nucleotide 729 and G to A at nucleotide 758). The C/T polymorphism at 729 site was not associated with the increased risk of gastric cancer (P=.961, OR=1.044, 95%CI: 0.187-5.818); however, G/A polymorphism at nucleotide 758 increased the risk of gastric cancer (P=.017, OR=1.923, 95%CI: 1.119-3.305). Luciferase reporter constructs containing the 758A allele showed higher luciferase activity compared with the wild-type allele, which indicated that 758 G>A in 3'-UTR increased PHB expression.

Conclusions: The G to A transition but not the C-to-T transition in the 3'-UTR of prohibitin was associated with an increased risk of gastric cancer in Chinese population.