Genetic variants in telomere-maintenance genes are associated with ovarian cancer risk and outcome Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Saturday, November 12, 2016

Genetic variants in telomere-maintenance genes are associated with ovarian cancer risk and outcome

 Telomeres are an essential part of human cells that affect how our cells age. 1,2. Telomeres are the caps at the end of each strand of DNA that protect our chromosomes, like the plastic tips at the end of shoelaces. 3.
open access

 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 (SNPs) 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 SNPs from two genes showed nominally significant associations with the risks of ovarian cancer. The most significant SNP was TEP1: 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 SNPs with outcome, although none of the associations had a Q < 0.05. Seven SNPs 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 SNPs from four genes showed suggestive associations with therapeutic response (P < 0.05). In a survival tree analysis, TEP1:rs10143407 was the primary factor contributing to overall survival. Unfavourable genotype analysis showed a cumulative effect of significant SNPs on ovarian cancer risk, survival and therapeutic response. Genetic variations in telomere-maintenance genes may be associated with ovarian cancer risk and outcome.

Study population

Patients (n = 417) with pathologically confirmed ovarian cancer were recruited from the University of Texas MD Anderson Cancer Center from 1998 to 2011. All case participants were newly diagnosed, histologically confirmed ovarian cancer and previously untreated before enrolment. There were no age, ethnicity or cancer stage restrictions on recruitment. Healthy control participants (n = 417) were recruited from Kelsey-Seybold Clinic, a large multi-specialty physician group in Houston metropolitan area. Controls without cancer history other than non-melanoma skin cancer were recruited during the same time period as the cases, and were matched to cases on age (±5 year) and ethnicity......... Epidemiologic data including demographics, tobacco use history, bw and height, history of cancer, and medical history were collected for all cases and controls. Information on vital status was obtained from the medical records and the Social Security Death Index. For each participant, a blood sample was drawn into coded heparinized tubes for lymphocyte isolation and DNA extraction.

In summary, this study provides epidemiologic evidence for the associations of telomere-maintenance gene variations with ovarian cancer risk and clinical outcome. Future studies are warranted to validate our findings and explore the biological mechanisms underlying the association of telomere maintenance gene variants with ovarian cancer risks and outcome.


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