Association of potentially functional genetic variants of PLCE1 with gallbladder cancer susceptibility in north Indian population.

BACKGROUND AND OBJECTIVES

Phospholipase C epsilon 1 (PLCE1) plays crucial roles in carcinogenesis and progression of esophageal and gastric cancers. In the present study, we investigated association of GWAS identified rs2274223 A>G and. rs7922612 T>C polymorphism of PLCE1 with susceptibility to gallbladder cancer (GBC).

METHODS

The study involved genotyping of selected PLCE1 variants in 416 GBC cases and 225 controls. Haplotype analysis was done by SNPStats. In silico analyses were performed using bioinformatic tools.

RESULTS

PLCE1 rs2274223 [AG] and rs7922612 [CC] genotypes were found to be significantly associated with an increased risk of GBC [OR = 1.9, p = 0.002; OR = 2.0, p = 0.04, respectively]. PLCE1 haplotype [Grs2274223-Crs7922612] also showed significant association with GBC [OR = 1.8, p = 0.04]. The association was significant in females and GBC patients with stones and female GBC patients with gallstones [OR = 2.6, p = 0.01; OR = 3.3, p = 0.007], respectively. However, no significant associations with other risk factors such as tobacco usage and age of onset were found. Functional prediction of rs2274223 A>G suggested change in protein coding and splicing regulation.

CONCLUSION

The present study found a significant association of PLCE1 rs2274223 and rs7922612 polymorphisms with susceptibility to GBC probably through gallstone-mediated inflammatory pathway.