Two novel polymorphisms in PLCE1 are associated with the susceptibility to esophageal squamous cell carcinoma in Chinese population.

Abstract

Esophageal cancer is the sixth leading cause of cancer-associated death worldwide. Phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. To evaluate the association between the single nucleotide polymorphisms (SNPs) in PLCE1 gene and ESCC risk, a case-control study including 550 patients with ESCC and 550 age, gender-matched controls was carried out to investigate the genetic susceptibility of three SNPs (rs3765524 C/T and two unreported potentially functional SNPs rs10882379 G/A and rs829232 G/A) as well as the interactions of gene-gene and gene-environment in the development of ESCC. And the results showed that GA genotype of rs10882379 was significantly associated with reduced ESCC risk compared with GG genotype (adjusted OR [95% CI]: 0.66 [0.51, 0.86]), while AA genotype of rs829232 was significantly associated with increased ESCC risk compared with GG genotype (adjusted OR [95% CI]: 1.37 [1.12, 1.67]). The haplotype analysis showed increased ESCC risk in Grs10882379Crs3765524Ars829232 and Grs10882379Trs3765524Ars829232 haplotypes with OR (95% CI) of 1.40 (1.13, 1.73) and 1.66 (1.18, 2.34), respectively and inversely reduced ESCC risk in Ars10882379Crs3765524Grs829232 haplotype with OR (95% CI) of 0.74 (0.61, 0.91). The gene-environment interaction analysis emerged a best model consisted of four factors (rs10882379, rs3765524, rs829232 and family history of ESCC) that could increase the ESCC risk in the 'high risk group' with 4.45-fold (OR [95% CI]: 5.45 [4.13, 7.19]), compared to the 'low risk group.' Our results further validate that the SNPs in PLCE1 gene may contribute to the ESCC susceptibility in Chinese Han population. Also the gene-gene and gene-environment interactions play a certain crucial role in the ESCC progression.

• Authors: Y Qu, S Zhang, L Cui, K Wang, C Song, P Wang, J Zhang, L Dai
• Journal: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus (Dis Esophagus) Vol. 30 Issue 1 Pg. 1-7 (Jan 01 2017) ISSN: 1442-2050 [Electronic] United States
• PMID: 27061010 (Publication Type: Journal Article)
• Copyright: © 2016 International Society for Diseases of the Esophagus.

Chemical References

• Phosphoinositide Phospholipase C
• phospholipase C epsilon

Topics

• Adult
• Aged
• Asian People (genetics)
• Carcinoma, Squamous Cell (genetics)
• Case-Control Studies
• Chin
• Epistasis, Genetic
• Esophageal Neoplasms (genetics)
• Esophageal Squamous Cell Carcinoma
• Female
• Gene-Environment Interaction
• Genetic Predisposition to Disease
• Genotype
• Haplotypes
• Humans
• Male
• Middle Aged
• Odds Ratio
• Phosphoinositide Phospholipase C (genetics)
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide
• Young Adult