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Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study.

ABSTRACT: BACKGROUND:Telomeres cap the ends of chromosomes and help maintain genomic stability and integrity. Telomere length (TL) has been linked to a number of diseases, including a variety of cancers; however, the association between TL and risk for colorectal cancer is unclear. METHODS:We investigate the association between genetic, diet, and lifestyle factors and TL and the association between TL and colorectal cancer using data from a population-based case-control study of colon (249 cases and 371 controls) and rectal cancer (276 cases and 372 controls) conducted in Utah. DNA samples came from immortalized cell lines for colon cancer and directly from whole blood for rectal cancer. We genotyped 11 single nucleotide polymorphisms in five genes associated with telomeres, TERT, MEN1, MRE11A, RECQL5, and TNKS. RESULTS:TL was measured using quantitative PCR. TERT rs2853676 (p=0.044) and RECQL5 rs820152 (p=0.001) were associated with TL at <0.05 level of significance. After adjusting for age and sex, BMI and cigarette smoking were significantly inversely associated with TL among controls. Use of aspirin/NSAIDs interacted significantly with TERT rs10069690 and rs2242652 to alter TL. Longer TL was significantly associated with reduced colon cancer risk after adjusting for age and sex (OR = 0.94 95% confidence intervals 0.89-0.99 per decile of TL). Further adjustment for BMI and cigarette smoking attenuated the association so that it was no longer significant. CONCLUSIONS:In summary several genetic and lifestyle factors were observed to influence TL. These factors also appear to confound associations between TL and colon cancer.

SUBMITTER: Pellatt AJ

PROVIDER: S-EPMC3459220 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study.

Pellatt Andrew J AJ Wolff Roger K RK Lundgreen Abbie A Cawthon Richard R Slattery Martha L ML

International journal of molecular epidemiology and genetics 20120831 3

<h4>Background</h4>Telomeres cap the ends of chromosomes and help maintain genomic stability and integrity. Telomere length (TL) has been linked to a number of diseases, including a variety of cancers; however, the association between TL and risk for colorectal cancer is unclear.<h4>Methods</h4>We investigate the association between genetic, diet, and lifestyle factors and TL and the association between TL and colorectal cancer using data from a population-based case-control study of colon (249 ...[more]

PMID: 23050049

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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.

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.

Dataset Information

Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study.

Publications

Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study.

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