Open AccessGenetic variants in telomere‐maintenance genes are associated with ovarian cancer risk and outcome
Author(s) -
Sun Yuhui,
Tao Wade,
Huang Maosheng,
Wu Xifeng,
Gu Jian
Publication year - 2017
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.12995
Subject(s) - single nucleotide polymorphism , ovarian cancer , telomere , biology , genotype , oncology , snp , hazard ratio , medicine , cancer , allele , genetics , gene , confidence interval
Most ovarian cancer patients present at an advanced stage with poor prognosis. Telomeres play a critical role in protecting chromosomes stability. The associations of genetic variants in telomere maintenance genes and ovarian cancer risk and outcome are unclear. We genotyped 137 single nucleotide polymorphisms ( SNP s) in telomere‐maintenance genes in 417 ovarian cancer cases and 417 matched healthy controls to evaluate their associations with cancer risk, survival and therapeutic response. False discovery rate Q ‐value was calculated to account for multiple testing. Eleven SNP s from two genes showed nominally significant associations with the risks of ovarian cancer. The most significant SNP was TEP 1 : rs2228026 with participants carrying at least one variant allele exhibiting a 3.28‐fold (95% CI : 1.72‐6.29; P < 0.001, Q = 0.028) increased ovarian cancer risk, which remained significant after multiple testing adjusting. There was also suggested evidence for the associations of SNP s with outcome, although none of the associations had a Q < 0.05. Seven SNP s from two genes showed associations with ovarian cancer survival ( P < 0.05). The strongest association was found in TNKS gene (rs10093972, hazard ratio = 1.88; 95% CI : 1.20‐2.92; P = 0.006, Q = 0.076). Five SNP s from four genes showed suggestive associations with therapeutic response ( P < 0.05). In a survival tree analysis, TEP 1 :rs10143407 was the primary factor contributing to overall survival. Unfavourable genotype analysis showed a cumulative effect of significant SNP s on ovarian cancer risk, survival and therapeutic response. Genetic variations in telomere‐maintenance genes may be associated with ovarian cancer risk and outcome.