Dataset Information

Telomere length and genetic analyses in population-based studies of endometrial cancer risk.

ABSTRACT: Telomeres are protective structures at the ends of linear chromosomes, regulated by a host of associated proteins. When telomeres become dysfunctional, genomic instability ensues. The vast majority of cells undergo apoptosis, although a rare cell may survive and become tumorigenic.The authors used conditional logistic regression to examine relative telomere length in peripheral blood leukocytes, genetic variants at telomere maintenance gene loci (TERT, TNKS2, POT1, TERF1, TERF2), and endometrial cancer risk in case-control studies nested within the Nurses' Health Study and the Women's Health Study.Relative telomere length was significantly inversely correlated with body mass index and weight gain since age 18 years. The authors did not observe a relationship between relative telomere length and endometrial cancer risk. Women in the shortest quartile had a multivariate-adjusted odds ratio (OR) of 1.20 (95% confidence interval [95% CI], 0.73-1.96; P for trend = .37) compared with women in the longest quartile. The authors found an elevation in endometrial cancer risk among women carrying at least 1 minor allele of RS2736122 (TERT; OR, 1.18; 95% CI, 1.01-1.38) or RS12412538 (TNKS2; OR, 1.16; 95% CI, 1.00-1.34).Relative telomere length was not associated with endometrial cancer risk. Other aspects of telomere maintenance remain to be explored.

SUBMITTER: Prescott J

PROVIDER: S-EPMC2978514 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Telomere length and genetic analyses in population-based studies of endometrial cancer risk.

Prescott Jennifer J McGrath Monica M Lee I-Min IM Buring Julie E JE De Vivo Immaculata I

Cancer 20100901 18

<h4>Background</h4>Telomeres are protective structures at the ends of linear chromosomes, regulated by a host of associated proteins. When telomeres become dysfunctional, genomic instability ensues. The vast majority of cells undergo apoptosis, although a rare cell may survive and become tumorigenic.<h4>Methods</h4>The authors used conditional logistic regression to examine relative telomere length in peripheral blood leukocytes, genetic variants at telomere maintenance gene loci (TERT, TNKS2, P ...[more]

PMID: 20549820

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Project description:BackgroundTelomeres at the ends of eukaryotic chromosomes play a critical role in maintaining the integrity and stability of the genome and participate in the initiation of DNA damage/repair responses.MethodsWe performed a case-control study to evaluate the role of three SNPs (TERT-07, TERT-54 and POT1-03) in telomere maintenance genes previously found to be significantly associated with breast cancer risk. We used sister-sets obtained from the New York site of the Breast Cancer Family Registry (BCFR). Among the 313 sister-sets, there were 333 breast cancer cases and 409 unaffected sisters who were evaluated in the current study. We separately applied conditional logistic regression and generalized estimating equations (GEE) models to evaluate associations between the three SNPs and breast cancer risk within sister-sets. We examined the associations between genotype, covariates and telomere length among unaffected sisters using a GEE model.ResultsWe found no significant associations between the three SNPs in telomere maintenance genes and breast cancer risk by both conditional logistic regression and GEE models, nor were these SNPs significantly related to telomere length. Among unaffected sisters, shortened telomeres were statistically significantly correlated with never hormone replacement therapy (HRT) use. Increased duration of HRT use was significantly associated with reduced telomere length. The means of telomere length were 0.77 (SD = 0.35) for never HRT use, 0.67 (SD = 0.29) for HRT use < 5 yrs and 0.59 (SD = 0.24) for HRT use ? 5 yrs after adjusting for age of blood donation and race and ethnicity.ConclusionsWe found that exogenous hormonal exposure was inversely associated with telomere length. No significant associations between genetic variants and telomere length or breast cancer risk were observed. These findings provide initial evidence to understand hormonal exposure in the regulation of telomere length and breast cancer risk but need replication in prospective studies.

Project description:Background: Previous studies have revealed associations between psychiatric disorder diagnosis and shorter telomere length. Here, we attempt to discern whether genetic risk for psychiatric disorders, or use of pharmacological treatments (i.e., antidepressants), predict shorter telomere length and risk for aging-related disease in a United Kingdom population sample. Methods: DNA samples from blood were available from 351 participants who were recruited as part of the South East London Community Health (SELCoH) Study, and for which whole-genome genotype data was available. Leukocyte telomere length was characterized using quantitative polymerase chain reactions. Individualized polygenic risk scores for major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) were calculated using Psychiatric Genomics Consortium summary statistics. We subsequently performed linear models, to discern the impact polygenic risk for psychiatric disorders (an etiological risk factor) and antidepressant use (common pharmacological treatment) have on telomere length, whilst accounting for other lifestyle/health factors (e.g., BMI, smoking). Results: There were no significant associations between polygenic risk for any of the psychiatric disorders tested and telomere length (p > 0.05). Antidepressant use was significantly associated with shorter telomere length and this was independent from a depression diagnosis or current depression severity (p ? 0.01). Antidepressant use was also associated with a significantly higher risk of aging-related disease, which was independent from depression diagnosis (p ? 0.05). Conclusion: Genetic risk for psychiatric disorders is not associated with shorter telomere length. Further studies are now needed to prospectively characterize if antidepressant use increases risk for aging-related disease and telomere shortening, or whether people who age faster and have aging-related diseases are just more likely to be prescribed antidepressants.

Dataset Information

Telomere length and genetic analyses in population-based studies of endometrial cancer risk.

Publications

Telomere length and genetic analyses in population-based studies of endometrial cancer risk.

Similar Datasets

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