Leukocyte Telomere Length and All-Cause, Cardiovascular Disease, and Cancer Mortality: Results From Individual-Participant-Data Meta-Analysis of 2 Large Prospective Cohort Studies

Mons, Ute; Müezzinler, Aysel; Schöttker, Ben; Dieffenbach, Aida Karina; Butterbach, Katja; Schick, Matthias; Peasey, Anne; Vivo, Immaculata De; Trichopoulou, Antonia; Boffetta, Paolo; Brenner, Hermann

doi:10.1093/aje/kww210

Cited by 96 publications

(79 citation statements)

References 41 publications

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“…5 Telomeres are nucleoprotein structures that preserve the ends of linear chromosomes, 6 and their shortening is linked to mortality, cancer, and cardiovascular disease. 7 Short telomeres drive cell senescence, resulting in inhibited tissue repair capacity and function. 6 The role of telomere shortening in lung health has been examined in adults but studies are lacking in children.…”

Section: Introductionmentioning

confidence: 99%

Telomere length and lung function in a population‐based cohort of children and mid‐life adults

Nguyen

Saffery

Burgner

et al. 2019

Pediatric Pulmonology

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Objective Telomere length is associated with poorer lung health in older adults, possibly from cumulative risk factor exposure, but data are lacking in pediatric and population‐based cohorts. We examined associations of telomere length with lung function in children and mid‐life adults. Methods Data were drawn from a population‐based cross‐sectional study of 11 to 12 year‐olds and mid‐life adults. Lung function was assessed by spirometric FEV1, FVC, FEV 1/FVC ratio, and MMEF 25‐75. Telomere length was measured by quantitative polymerase chain reaction from blood and expressed as the amount of telomeric genomic DNA to the beta‐globin gene (T/S ratio). Associations of telomere length with spirometric parameters were tested by linear and logistic regression models, adjusting for potential confounders of sex, age, body mass index, socioeconomic position, physical activity, inflammation, asthma, pubertal status, and smoking. Results Mean T/S ratio was 1.09 (n = 1206; SD 0.55) in children and 0.81 (n = 1343; SD 0.38) in adults. In adults, for every additional unit in T/S ratio, FEV 1/FVC and MMEF 25‐75 z‐scores were higher (β 0.21 [95% confidence interval, CI; 0.06‐0.36] and 0.23 [95% CI; 0.08‐0.38], respectively), and the likelihood of being in the lowest quartile for FEV 1/FVC and MMEF 25‐75 z‐scores was lower (odds ratios 0.59 [95% CI, 0.39‐0.89] and 0.64 [95% CI, 0.41‐0.99], respectively). No evidence of association was seen for adult FEV 1 or FVC, or any childhood spirometric index after adjustments. Conclusion Shorter telomere length showed moderate associations with poorer airflow parameters, but not vital capacity (lung volume) in mid‐life adults. However, there was no convincing evidence of associations in children.

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Section: Introductionmentioning

confidence: 99%

Telomere length and lung function in a population‐based cohort of children and mid‐life adults

Nguyen

Saffery

Burgner

et al. 2019

Pediatric Pulmonology

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“…Telomere length exhibits high interindividual variability and is suggested to reflect the cumulative burden of both genetic and lifestyle factors . Clinical studies have shown that short leukocyte telomere length (LTL) is associated with increased risk for aging‐related diseases, including diabetes, diabetic kidney disease, cardiovascular diseases and all‐cause mortality …”

Section: Introductionmentioning

confidence: 99%

“…9,10 Clinical studies have shown that short leukocyte telomere length (LTL) is associated with increased risk for aging-related diseases, including diabetes, diabetic kidney disease, cardiovascular diseases and all-cause mortality. [11][12][13][14] Ethnic disparities in prevalence and risk factors for obesity are well documented. Previously, ethnic disparities in high-sensitivity C-reactive protein (hs-CRP), adiponectin, and insulin resistance (IR) in the local population in Singapore were reported and, interestingly, an increase in body mass index (BMI) was associated with a greater change in hs-CRP, adiponectin, and IR in Chinese individuals compared with Malays and Indians.…”

Section: Introductionmentioning

confidence: 99%

Ethnic disparities in relationships of obesity indices with telomere length in Asians with type 2 diabetes

Gurung

Yiamunaa

Liu

et al. 2018

Journal of Diabetes

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Background Obesity and shorter telomeres increase the risk for diabetes complications and mortality. However, the relationship between obesity and telomere length in diverse Asian populations with type 2 diabetes (T2D) is not well understood. This study examined the association of baseline and changes in obesity indices with telomere length in multiethnic Asian populations with T2D. Methods Leukocyte telomere length (LTL) was measured by quantitative polymerase chain reaction in the SMART2D cohort (n = 1431 at baseline, n = 1039 after 3.2 years median follow‐up). Associations between obesity indices and LTL were assessed by linear regression. Results Compared with Chinese, LTL was longer in Malays (P < 0.0001) and similar in Indians. Cross‐sectionally, body mass index (BMI)‐adjusted (residual) visceral fat area (VFA; β = −0.004, P = 0.006), and waist‐to‐hip ratio (β = −1.95, P = 0.030) were significantly associated with LTL in Chinese but not in Malays and Indians. Changes in BMI (r = −0.080; P = 0.053) and VFA (r = −0.126; P = 0.002) were inversely correlated with changes in LTL only in Chinese. Furthermore, in Chinese, 1‐SD incremental changes in BMI (β = −0.070; P = 0.040) and VFA (β = −0.088, P = 0.028) were significantly associated with larger telomere attrition, independent of age, sex, diabetes condition, baseline LTL, obesity, and inflammation markers. Conclusions Three‐year changes in BMI and VFA were associated with telomere dynamics in Chinese but not in Malays and Indians with T2D. Reducing obesity may reduce the risk of diabetes complications associated with shorter LTL in the Chinese population.

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“…Age, as a continuous variable, male gender, Stage IV, were all significantly associated with poor survival. As short or long blood telomere lengths had been reported for association with cancer deaths,18,20,23,25,26 we hypothesize that both short and long blood telomere lengths may be associated with poor survival in NPC patients. Log TSR between 20.411 and 20.152) by univariate analysis with Cox regression (HR, 95% CI 5 1.323, 1.059-1.652, p 5 0.014)…”

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confidence: 68%

Leukocyte telomere length associates with nasopharyngeal carcinoma risk and survival in Hong Kong Chinese

Tsang

Dai

et al. 2018

Intl Journal of Cancer

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Telomere shortening occurs as an early event in tumorigenesis. The TERT-CLPTM1L locus associates with nasopharyngeal carcinoma (NPC) risk. It remains unknown if leukocyte telomere length (LTL) associates with NPC risk and survival. The relative LTL (rLTL) was measured by quantitative-PCR in 2,996 individuals comprised of 1,284 NPC cases and 1712 matched controls. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression. The hazard ratio (HR) and 95% CI were calculated by Cox regression for survival analysis with rLTL and other clinical parameters in 1,243 NPC with a minimum follow-up period of 25 months. NPC patients had significantly shorter telomere length than controls. Shorter rLTL significantly associated with increased NPC risk, when the individuals were dichotomized into long and short telomeres based on median-split rLTL in the control group (OR = 2.317; 95% CI = 1.989-2.700, p = 4.10 × 10 ). We observed a significant dose-response association (p = 3.26 × 10 ) between rLTL and NPC risk with OR being 3.555 (95% CI = 2.853-4.429) for the individuals in the first quartile (shortest) compared with normal individuals in the fourth quartile (longest). A multivariate Cox regression analysis adjusted by age demonstrated an independent effect of rLTL on NPC survival for late-stage NPC patients, when the individuals were categorized into suboptimal rLTL versus the medium rLTL based on a threshold set from normal (HR = 1.471, 95% CI = 1.056-2.048, p = 0.022). Shorter blood telomeres may be markers for higher susceptibility for NPC risk. Suboptimal rLTL may be a poor prognostic factor for advanced NPC patients, as it associates independently with poor survival.

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Leukocyte Telomere Length and All-Cause, Cardiovascular Disease, and Cancer Mortality: Results From Individual-Participant-Data Meta-Analysis of 2 Large Prospective Cohort Studies

Cited by 96 publications

References 41 publications

Telomere length and lung function in a population‐based cohort of children and mid‐life adults

Telomere length and lung function in a population‐based cohort of children and mid‐life adults

Ethnic disparities in relationships of obesity indices with telomere length in Asians with type 2 diabetes

Leukocyte telomere length associates with nasopharyngeal carcinoma risk and survival in Hong Kong Chinese

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