共查询到20条相似文献,搜索用时 15 毫秒
1.
Peter Willeit Julia Raschenberger Emma E. Heydon Sotirios Tsimikas Margot Haun Agnes Mayr Siegfried Weger Joseph L. Witztum Adam S. Butterworth Johann Willeit Florian Kronenberg Stefan Kiechl 《PloS one》2014,9(11)
Background
Short telomeres have been linked to various age-related diseases. We aimed to assess the association of telomere length with incident type 2 diabetes mellitus (T2DM) in prospective cohort studies.Methods
Leucocyte relative telomere length (RTL) was measured using quantitative polymerase chain reaction in 684 participants of the prospective population-based Bruneck Study (1995 baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n = 479). Hazard ratios for T2DM were calculated across quartiles of baseline RTL using Cox regression models adjusted for age, sex, body-mass index, smoking, socio-economic status, physical activity, alcohol consumption, high-density lipoprotein cholesterol, log high-sensitivity C-reactive protein, and waist-hip ratio. Separate analyses corrected hazard ratios for within-person variability using multivariate regression calibration of repeated measurements. To contextualise findings, we systematically sought PubMed, Web of Science and EMBASE for relevant articles and pooled results using random-effects meta-analysis.Results
Over 15 years of follow-up, 44 out of 606 participants free of diabetes at baseline developed incident T2DM. The adjusted hazard ratio for T2DM comparing the bottom vs. the top quartile of baseline RTL (i.e. shortest vs. longest) was 2.00 (95% confidence interval: 0.90 to 4.49; P = 0.091), and 2.31 comparing the bottom quartile vs. the remainder (1.21 to 4.41; P = 0.011). The corresponding hazard ratios corrected for within-person RTL variability were 3.22 (1.27 to 8.14; P = 0.014) and 2.86 (1.45 to 5.65; P = 0.003). In a random-effects meta-analysis of three prospective cohort studies involving 6,991 participants and 2,011 incident T2DM events, the pooled relative risk was 1.31 (1.07 to 1.60; P = 0.010; I 2 = 69%).Conclusions/Interpretation
Low RTL is independently associated with the risk of incident T2DM. To avoid regression dilution biases in observed associations of RTL with disease risk, future studies should implement methods correcting for within-person variability in RTL. The causal role of short telomeres in T2DM development remains to be determined. 相似文献2.
Purpose
Both telomere length and mitochondrial function are accepted as reflective indices of aging. Recent studies have shown that telomere dysfunction may influence impaired mitochondrial biogenesis and function. However, there has been no study regarding the possible association between telomere and mitochondrial function in humans. Therefore, the purpose of the study was to identify any relationships between mitochondrial and telomere function.Methods
The present study included 129 community-dwelling, elderly women. The leukocyte mitochondrial DNA copy number and telomere length were measured using a quantitative real-time polymerase chain reaction method. Anthropometric measurement, biochemical blood testing, a depression screening questionnaire using a 15-question geriatric depression scale (GDS-15), and a cognitive function test using the Korean version of the mini mental state examination (K-MMSE) were performed.Results
Leukocyte mtDNA copy number was positively associated with telomere length (r=0.39, p=<0.0001) and K-MMSE score (r=0.06, p=0.02). Additionally, leukocyte mtDNA copy number was negatively correlated with GDS-15 score (r=-0.17, p=0.04). Age (r=-0.15, p=0.09), waist circumference (r=-0.16, p=0.07), and serum ferritin level (r=-0.13, p=0.07) tended to be inversely correlated with leukocyte mtDNA copy number. With a stepwise multiple regression analysis, telomere length was found to be an independent factor associated with leukocyte mtDNA copy number after adjustment for confounding variables including age, body mass index, waist circumference, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, hs-CRP, serum ferritin, HOMA-IR, K-MMSE, GDS-15, hypertension, diabetes, dyslipidemia, currently smoking, alcohol drinking, and regular exercise.Conclusions
This study showed that leukocyte mtDNA copy number was positively correlated with leukocyte telomere length in community-dwelling elderly women. Our findings suggest that telomere function may influence mitochondrial function in humans. 相似文献3.
Sarah Jodczyk David M. Fergusson L. John Horwood John F. Pearson Martin A. Kennedy 《PloS one》2014,9(5)
Telomeres are specialised structures that cap the ends of chromosomes. They shorten with each cell division and have been proposed as a marker of cellular aging. Previous studies suggest that early life stressors increase the rate of telomere shortening with potential impact on disease states and mortality later in life. This study examined the associations between telomere length and exposure to a number of stressors that arise during development from the antenatal/perinatal period through to young adulthood. Participants were from the Christchurch Health and Development Study (CHDS), a New Zealand longitudinal birth cohort which has followed participants from birth until age 30. Telomere length was obtained on DNA from peripheral blood samples collected from consenting participants (n = 677) at age 28–30, using a quantitative PCR assay. These data were assessed for associations with 26 measures of life course adversity or stress which occurred prior to 25 years of age. No associations were found between telomere length measured at age 28–30 years and life course adversity or stress for specific measures and for the summary risk scores for each developmental domain. The correlations were very small ranging from −0.06 to 0.06 with a median of 0.01, and none were statistically significant. Our results in this well-studied birth cohort do not support prior reports of such associations, and underscore the need for more extensive replication of proposed links between stress and telomere biology in larger cohorts with appropriate phenotypic data. 相似文献
4.
Bas C. T. van Bussel Isabel Ferreira Marjo P. H. van de Waarenburg Marleen M. J. van Greevenbroek Carla J. H. van der Kallen Ronald M. A. Henry Edith J. M. Feskens Coen D. A. Stehouwer Casper G. Schalkwijk 《PloS one》2013,8(3)
Background
In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available.Methods
We measured, in a large ongoing cohort study (n = 574), by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD) and single-biomarker techniques (ELISA or immunoturbidimetric assay), the following biomarkers of low-grade inflammation: C-reactive protein (CRP), serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects’ cardiovascular risk factors by ANOVA.Results
Despite that both methods ranked individuals’ levels of biomarkers very similarly (Pearson’s r all≥0.755) absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP), 0.711 (SAA), 0.895 (sICAM-1) and 0.858 (sVCAM-1). Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method.Conclusions
Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies. 相似文献5.
Eva M. Kingma Peter de Jonge Pim van der Harst Johan Ormel Judith G. M. Rosmalen 《PloS one》2012,7(11)
Low intelligence has been associated with poor health and mortality, but underlying mechanisms remain obscure. We hypothesized that low intelligence is associated with accelerated biological ageing as reflected by telomere length; we suggested potential mediation of this association by unhealthy behaviors and low socioeconomic position. The study was performed in a longitudinal population-based cohort study of 895 participants (46.8% males). Intelligence was measured with the Generalized Aptitude-Test Battery at mean age 52.8 years (33–79 years, SD = 11.3). Leukocyte telomere length was measured by PCR. Lifestyle and socioeconomic factors were assessed using written self-report measures. Linear regression analyses, adjusted for age, sex, and telomere length measured at the first assessment wave (T1), showed that low intelligence was associated with shorter leukocyte telomere length at approximately 2 years follow-up (beta = .081, t = 2.160, p = .031). Nearly 40% of this association was explained by an unhealthy lifestyle, while low socioeconomic position did not add any significant mediation. Low intelligence may be a risk factor for accelerated biological ageing, thereby providing an explanation for its association with poor health and mortality. 相似文献
6.
Tissue damage or pathological alterations are not detectable in the majority of people with whiplash associated disorders (WAD). Widespread hyperalgisa, morphological muscle changes and psychological distress are common features of WAD. However little is known about the presence of inflammation and its association with symptom persistence or the clinical presentation of WAD. This study aimed to prospectively investigate changes in serum inflammatory biomarker levels from the acute (<3 weeks) to chronic (>3 months) stages of whiplash injury. It also aimed to determine relationships between biomarker levels and hyperalgesia, fatty muscle infiltrates of the cervical extensors identified on MRI and psychological factors. 40 volunteers with acute WAD and 18 healthy controls participated. Participants with WAD were classified at 3 months as recovered/mild disability or having moderate/severe disability using the Neck Disability Index. At baseline both WAD groups showed elevated serum levels of CRP but by 3 months levels remained elevated only in the moderate/severe group. The recovered/mild disability WAD group had higher levels of TNF-α at both time points than both the moderate/severe WAD group and healthy controls. There were no differences found in serum IL-1β. Moderate relationships were found between hyperalgesia and CRP at both time points and between hyperalgesia and IL-1β 3 months post injury. There was a moderate negative correlation between TNF-α and amount of fatty muscle infiltrate and pain intensity at 3 months. Only a weak relationship was found between CRP and pain catastrophising and no relationship between biomarker levels and posttraumatic stress symptoms. The results of the study indicate that inflammatory biomarkers may play a role in outcomes following whiplash injury as well as being associated with hyperalgesia and fatty muscle infiltrate in the cervical extensors. 相似文献
7.
Dana A. Glei Noreen Goldman Rosa Ana Risques David H. Rehkopf William H. Dow Luis Rosero-Bixby Maxine Weinstein 《PloS one》2016,11(4)
Telomere length has generated substantial interest as a potential predictor of aging-related diseases and mortality. Some studies have reported significant associations, but few have tested its ability to discriminate between decedents and survivors compared with a broad range of well-established predictors that include both biomarkers and commonly collected self-reported data. Our aim here was to quantify the prognostic value of leukocyte telomere length relative to age, sex, and 19 other variables for predicting five-year mortality among older persons in three countries. We used data from nationally representative surveys in Costa Rica (N = 923, aged 61+), Taiwan (N = 976, aged 54+), and the U.S. (N = 2672, aged 60+). Our study used a prospective cohort design with all-cause mortality during five years post-exam as the outcome. We fit Cox hazards models separately by country, and assessed the discriminatory ability of each predictor. Age was, by far, the single best predictor of all-cause mortality, whereas leukocyte telomere length was only somewhat better than random chance in terms of discriminating between decedents and survivors. After adjustment for age and sex, telomere length ranked between 15th and 17th (out of 20), and its incremental contribution was small; nine self-reported variables (e.g., mobility, global self-assessed health status, limitations with activities of daily living, smoking status), a cognitive assessment, and three biological markers (C-reactive protein, serum creatinine, and glycosylated hemoglobin) were more powerful predictors of mortality in all three countries. Results were similar for cause-specific models (i.e., mortality from cardiovascular disease, cancer, and all other causes combined). Leukocyte telomere length had a statistically discernible, but weak, association with mortality, but it did not predict survival as well as age or many other self-reported variables. Although telomere length may eventually help scientists understand aging, more powerful and more easily obtained tools are available for predicting survival. 相似文献
8.
Alice Hadchouel Laetitia Marchand-Martin Marie-Laure Franco-Montoya Laetitia Peaudecerf Pierre-Yves Ancel Christophe Delacourt EPIPAGEADO study group 《PloS one》2015,10(9)
Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25–75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease. 相似文献
9.
Anne Kouvonen Mika Kivim?ki Tuula Oksanen Jaana Pentti Roberto De Vogli Marianna Virtanen Jussi Vahtera 《PloS one》2013,8(10)
Background
Obesity and overweight are suggested to increase the risk of occupational injury but longitudinal evidence to confirm this is rare. We sought to evaluate obesity and overweight as risk factors for occupational injuries.Methodology/Principal Findings
A total of 69,515 public sector employees (80% women) responded to a survey in 2000–2002, 2004 or 2008. Body mass index (kg/m2) was derived from self-reported height and weight and was linked to records of subsequent occupational injuries obtained from national registers. Different injury types, locations and events or exposures (the manner in which the injury was produced or inflicted) were analyzed by body mass index category adjusting for baseline socio-demographic characteristics, work characteristics, health-risk behaviors, physical and mental health, insomnia symptoms, and sleep duration. During the mean follow-up of 7.8 years (SD = 3.2), 18% of the employees (N = 12,204) recorded at least one occupational injury. Obesity was associated with a higher overall risk of occupational injury; multivariable adjusted hazard ratio (HR) 1.21 (95% CI 1.14–1.27). A relationship was observed for bone fractures (HR = 1.37; 95% CI: 1.10–1.70), dislocations, sprains and strains (HR = 1.36; 95% CI: 1.25–1.49), concussions and internal injuries (HR = 1.26; 95% CI: 1.11–1.44), injuries to lower extremities (HR = 1.62; 95%: 1.46–1.79) and injuries to whole body or multiple sites (HR = 1.37; 95%: 1.10–1.70). Furthermore, obesity was associated with a higher risk of injuries caused by slipping, tripping, stumbling and falling (HR = 1.55; 95% CI: 1.40–1.73), sudden body movement with or without physical stress (HR = 1.24; 95% CI: 1.10–1.41) and shock, fright, violence, aggression, threat or unexpected presence (HR = 1.33; 95% CI: 1.03–1.72). The magnitude of the associations between overweight and injuries was smaller, but the associations were generally in the same direction as those of obesity.Conclusions/Significance
Obese employees record more occupational injuries than those with recommended healthy weight. 相似文献10.
11.
Tine Roman de Mettelinge Dirk Cambier Patrick Calders Nele Van Den Noortgate Kim Delbaere 《PloS one》2013,8(6)
Background
Older adults with type 2 Diabetes Mellitus are at increased risk of falling. The current study aims to identify risk factors that mediate the relationship between diabetes and falls.Methods
199 older adults (104 with diabetes and 95 healthy controls) underwent a medical screening. Gait (GAITRite®), balance (AccuGait® force plate), grip strength (Jamar®), and cognitive status (Mini-Mental State Examination and Clock Drawing Test) were assessed. Falls were prospectively recorded during a 12-month follow-up period using monthly calendars.Results
Compared to controls, diabetes participants scored worse on all physical and cognitive measures. Sixty-four participants (42 diabetes vs. 22 controls) reported at least one injurious fall or two non-injurious falls (“fallers”). Univariate logistic regression identified diabetes as a risk factor for future falls (Odds Ratio 2.25, 95%CI 1.21–4.15, p = 0.010). Stepwise multiple regressions defined diabetes and poor balance as independent risk factors for falling. Taking more medications, slower walking speed, shorter stride length and poor cognitive performance were mediators that reduced the Odds Ratio of the relationship between diabetes and faller status relationship the most followed by reduced grip strength and increased stride length variability.Conclusions
Diabetes is a major risk factor for falling, even after controlling for poor balance. Taking more medications, poorer walking performance and reduced cognitive functioning were mediators of the relationship between diabetes and falls. Tailored preventive programs including systematic medication reviews, specific balance exercises and cognitive training might be beneficial in reducing fall risk in older adults suffering from diabetes. 相似文献12.
Brian M. Nolen Randall E. Brand Denise Prosser Liudmila Velikokhatnaya Peter J. Allen Herbert J. Zeh William E. Grizzle Aleksey Lomakin Anna E. Lokshin 《PloS one》2014,9(4)
BackgroundThe clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools.MethodsSixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).ResultsThe panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone.ConclusionsMost biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection. 相似文献
13.
Telomeres, comprised of short repetitive sequences, are essential for genome stability and have been studied in relation to cellular senescence and aging. Telomerase, the enzyme that adds telomeric repeats to chromosome ends, is essential for maintaining the overall telomere length. A lack of telomerase activity in mammalian somatic cells results in progressive shortening of telomeres with each cellular replication event. Mammals exhibit high rates of cell proliferation during embryonic and juvenile stages but very little somatic cell proliferation occurs during adult and senescent stages. The telomere hypothesis of cellular aging states that telomeres serve as an internal mitotic clock and telomere length erosion leads to cellular senescence and eventual cell death. In this report, we have examined telomerase activity, processivity, and telomere length in Daphnia, an organism that grows continuously throughout its life. Similar to insects, Daphnia telomeric repeat sequence was determined to be TTAGG and telomerase products with five-nucleotide periodicity were generated in the telomerase activity assay. We investigated telomerase function and telomere lengths in two closely related ecotypes of Daphnia with divergent lifespans, short-lived D. pulex and long-lived D. pulicaria. Our results indicate that there is no age-dependent decline in telomere length, telomerase activity, or processivity in short-lived D. pulex. On the contrary, a significant age dependent decline in telomere length, telomerase activity and processivity is observed during life span in long-lived D. pulicaria. While providing the first report on characterization of Daphnia telomeres and telomerase activity, our results also indicate that mechanisms other than telomere shortening may be responsible for the strikingly short life span of D. pulex. 相似文献
14.
Marta Jackowska Mark Hamer Livia A. Carvalho Jorge D. Erusalimsky Lee Butcher Andrew Steptoe 《PloS one》2012,7(10)
Background
Shorter telomere length and poor sleep are more prevalent at older ages, but their relationship is uncertain. This study explored associations between sleep duration and telomere length in a sample of healthy middle and early old age people.Methods
Participants were 434 men and women aged 63.3 years on average drawn from the Whitehall II cohort study. Sleep duration was measured by self-report.Results
There was a linear association between sleep duration and leukocyte telomere length in men but not in women (P = 0.035). Men reporting shorter sleep duration had shorter telomeres, independently of age, body mass index, smoking, educational attainment, current employment, cynical hostility scores and depressive symptoms. Telomeres were on average 6% shorter in men sleeping 5 hours or fewer compared with those sleeping more than 7 hours per night.Conclusion
This study adds to the growing literature relating sleep duration with biomarkers of aging, and suggests that shortening of telomeres might reflect mechanisms through which short sleep contributes to pathological conditions in older men. 相似文献15.
Hannah S. Bender Elizabeth P. Murchison Hilda A. Pickett Janine E. Deakin Margaret A. Strong Carly Conlan Daniel A. McMillan Axel A. Neumann Carol W. Greider Gregory J. Hannon Roger R. Reddel Jennifer A. Marshall. Graves 《PloS one》2012,7(9)
Telomeres, specialised structures that protect chromosome ends, play a critical role in preserving chromosome integrity. Telomere dynamics in the Tasmanian devil (Sarcophilus harrisii) are of particular interest in light of the emergence of devil facial tumour disease (DFTD), a transmissible malignancy that causes rapid mortality and threatens the species with extinction. We used fluorescent in situ hybridisation to investigate telomere length in DFTD cells, in healthy Tasmanian devils and in four closely related marsupial species. Here we report that animals in the Order Dasyuromorphia have chromosomes characterised by striking telomere length dimorphism between homologues. Findings in sex chromosomes suggest that telomere length dimorphism may be regulated by events in the parental germlines. Long telomeres on the Y chromosome imply that telomere lengthening occurs during spermatogenesis, whereas telomere diminution occurs during oogenesis. Although found in several somatic cell tissue types, telomere length dimorphism was not found in DFTD cancer cells, which are characterised by uniformly short telomeres. This is, to our knowledge, the first report of naturally occurring telomere length dimorphism in any species and suggests a novel strategy of telomere length control. Comparative studies in five distantly related marsupials and a monotreme indicate that telomere dimorphism evolved at least 50 million years ago. 相似文献
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Shari S. Rogal Robert M. Arnold Michael Chapko Barbara V. Hanusa Ada Youk Galen E. Switzer Mary Ann Sevick Nichole K. Bayliss Carolyn L. Zook Alexis Chidi David S. Obrosky Susan L. Zickmund 《PloS one》2016,11(2)
Hepatitis C virus (HCV) treatment has the potential to cure the leading cause of cirrhosis and hepatocellular carcinoma. However, only those deemed eligible for treatment have the possibility of this cure. Therefore, understanding the determinants of HCV treatment eligibility is critical. Given that effective communication with and trust in healthcare providers significantly influences treatment eligibility decisions in other diseases, we aimed to understand patient-provider interactions in the HCV treatment eligibility process. This prospective cohort study was conducted in the VA Pittsburgh Healthcare System. Patients were recruited after referral for gastroenterology consultation for HCV treatment with interferon and ribavirin. Consented patients completed semi-structured interviews and validated measures of depression, substance and alcohol use, and HCV knowledge. Two coders analyzed the semi-structured interviews. Factors associated with patient eligibility for interferon-based therapy were assessed using multivariate logistic regression. Of 339 subjects included in this analysis, only 56 (16.5%) were deemed eligible for HCV therapy by gastroenterology (GI) providers. In the multivariate logistic regression, patients who were older (OR = 0.96, 95%CI = 0.92–0.99, p = .049), reported concerns about the GI provider (OR = 0.40, 95%CI = 0.10–0.87, p = 0.02) and had depression symptoms (OR = 0.32, 95%CI = 0.17–0.63, p = 0.001) were less likely to be eligible. Patients described barriers that included feeling stigmatized and poor provider interpersonal or communication skills. In conclusion, we found that patients’ perceptions of the relationship with their GI providers were associated with treatment eligibility. Establishing trust and effective communication channels between patients and providers may lower barriers to potential HCV cure. 相似文献
18.
Nuria Seguí Marta Pineda Elisabet Guinó Ester Borràs Matilde Navarro Fernando Bellido Victor Moreno Conxi Lázaro Ignacio Blanco Gabriel Capellá Laura Valle 《PloS one》2013,8(4)
Telomere length variation has been associated with increased risk of several types of tumors, and telomere shortening, with genetic anticipation in a number of genetic diseases including hereditary cancer syndromes. No conclusive studies have been performed for Lynch syndrome, a hereditary colorectal cancer syndrome caused by germline mutations in the DNA mismatch repair genes. Here we evaluate telomere length in Lynch syndrome, both as a cancer risk factor and as a mechanism associated with anticipation in the age of cancer onset observed in successive generations of Lynch syndrome families. Leukocyte telomere length was measured in 244 mismatch repair gene mutation carriers from 96 Lynch syndrome families and in 234 controls using a monochrome multiplex quantitative PCR method. Cancer-affected mutation carriers showed significantly shorter telomeres than cancer-free mutation carriers. In addition, cancer-affected carriers showed the most pronounced shortening of telomere length with age, compared with unaffected carriers. The anticipation in the age of cancer onset observed in successive generations was not associated with telomere shortening, although, interestingly, all mother-son pairs showed telomere shortening. In conclusion, cancer-affected mismatch repair gene mutation carriers have distinct telomere-length pattern and dynamics. However, anticipation in the age of onset is not explained by telomere shortening. Pending further study, our findings suggest that telomere attrition might explain the previously reported dependence of cancer risk on the parent-of-origin of mismatch repair gene mutations. 相似文献
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