Open AccessVariants in Notch signalling pathway genes, PSEN 1 and MAML 2, predict overall survival in Chinese patients with epithelial ovarian cancer
Author(s) -
Xu Yuan,
Cheng Lei,
Dai Hongji,
Zhang Ruoxin,
Wang Mengyun,
Shi Tingyan,
Sun Menghong,
Cheng Xi,
Wei Qingyi
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13764
Subject(s) - single nucleotide polymorphism , snp , genotype , proportional hazards model , biology , notch signaling pathway , gene , oncology , genetics , medicine , cancer research
To identify genetic variants in Notch signalling pathway genes that may predict survival of Han Chinese patients with epithelial ovarian cancer ( EOC ), we analysed a total of 1273 single nucleotide polymorphisms ( SNP s) within 75 Notch genes in 480 patients from a published EOC genomewide association study ( GWAS ). We found that PSEN 1 rs165934 and MAML 2 rs76032516 were associated with overall survival ( OS ) of patients by multivariate Cox proportional hazards regression analysis. Specifically, the PSEN 1 rs165934 AA genotype was associated with a poorer survival (adjusted hazards ratio [adj HR ] = 1.41, 95% CI = 1.07‐1.84, and P = .014), compared with the CC + CA genotype, while MAML 2 rs76032516 AA + AC genotypes were associated with a poorer survival (adj HR = 1.58, 95% CI = 1.16‐2.14, P = .004), compared with the CC genotype. The combined analysis of these two SNP s revealed that the death risk increased as the number of unfavourable genotypes increased in a dose‐dependent manner ( P trend < .001). Additionally, the expression quantitative trait loci analysis revealed that the SNP rs165932 in the rs165934 LD block ( r 2 = .946) was associated with expression levels of PSEN 1 , which might be responsible for the observed association with SNP rs165934. The associations of PSEN 1 rs165934 and MAML 2 rs76032516 of the Notch signalling pathway genes with OS in Chinese EOC patients are novel findings, which need to be validated in other large and independent studies.