Dataset Information

Urinary Phthalates and Leukocyte Telomere Length: An Analysis of NHANES 1999-2002.

ABSTRACT: The International Agency for Research on Cancer classified the di-2-ethylhexyl phthalate (DEHP) as "possibly carcinogenic to humans". In vitro studies reported that phthalate exposure resulted in induction of several nuclear transcription factors that are activators of telomerase reverse transcriptase (TERT) and telomerase activity of the human telomerase complex. The objective of this study was to determine whether there is an association between urinary phthalate metabolites [mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-(2-ethyl)-hexyl phthalate (MEHP), and mono-benzyl phthalate (MBzP) and leukocyte telomere length (LTL) in the adult population of the National Health and Nutrition Examination Survey (NHANES) 1999-2002 (n=2472). After adjustment for potential confounders, participants in the 3rd and 4th quartiles of urinary MEHP had statistically significantly longer LTL (5.34%, 95% CI: 1.31, 9.53; and 7.14%, 95% CI: 2.94, 11.63; respectively) compared to the lowest quartile, with evidence of a dose-response relationship (p-trend=0.01). The association remained when the analyses were stratified by age groups (20-39years, 40-59years, and 60years and older), and sex. Furthermore, MBP and MBzP were associated with higher LTL in older participants. The age independent association between longer LTL and MEHP (a metabolite of DEHP) might suggest a possible role of MEHP as tumor promoter.

SUBMITTER: Scinicariello F

PROVIDER: S-EPMC4856743 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Urinary Phthalates and Leukocyte Telomere Length: An Analysis of NHANES 1999-2002.

Scinicariello Franco F Feroe Aliya G AG Attanasio Roberta R

EBioMedicine 20160218

The International Agency for Research on Cancer classified the di-2-ethylhexyl phthalate (DEHP) as "possibly carcinogenic to humans". In vitro studies reported that phthalate exposure resulted in induction of several nuclear transcription factors that are activators of telomerase reverse transcriptase (TERT) and telomerase activity of the human telomerase complex. The objective of this study was to determine whether there is an association between urinary phthalate metabolites [mono-ethyl phthal ...[more]

PMID: 27211552

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Project description:Background/objectivesTelomere shortening is associated with age and risk of medical comorbidity. We assessed the relationship between measures of adiposity, leukocyte telomere length, and mortality and whether it is modified by age.Subjects/methodsSubjects with dual-energy X-ray absorptiometry measures were identified using the National Health and Nutrition Examination Survey 1999-2002. Obesity was categorized using two body fat definitions (BF1%: men ⩾25%; females ⩾35%; BF2% ⩾28% and ⩾38%, respectively), body mass index (BMI) and waist circumference (WC; men ⩾102 cm; females ⩾88 cm). Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative PCR. Weighted multivariable regression models evaluated the association of telomere length with adiposity, both continuously and categorically (low/normal BF%, low/high WC and standard BMI categories). Differences in telomere length by age and adiposity were ascertained and subsequent models were stratified by age. Proportional hazard models assessed the risk of mortality by adiposity status. A telomere by adiposity interaction was tested in the entire cohort and by age category (<60 vs ⩾60 years; <70 vs ⩾70 years).ResultsWe identified 7827 subjects. Mean age was 46.1 years. Overall telomere length was 1.05±0.01 (s.e.) that differed by BF1% (low/high: 1.12±0.02 vs 1.03±0.02; P<0.001), BF2% (1.02±0.02 vs 1.11±0.02; P<0.001), BMI (underweight 1.08±0.03; normal 1.09±0.02; overweight 1.04±0.02; and obese 1.03±0.02;P<0.001) and WC (low/high 1.09±0.02 vs 1.02±0.02; P<0.001). Adjusted β-coefficients evaluating the relationship between telomere length and adiposity (measured continuously) were as follows: BF1% (β=-0.0033±0.0008; P<0.001), BF2% (-0.041±0.008; P<0.001), BMI (β=-0.025±0.0008; P=0.005) and WC (β=-0.0011±0.0004; P=0.007). High BF% (BF1%: β=-0.035±0.011; P=0.002; BF2%: β=-0.041±0.008; P<0.001) and WC (β=-0.035±0.011; P=0.008) were inversely related to telomere length (TL). Stratifying by age, high BF1% (-0.061±0.013), BF2% (-0.065±0.01), BMI-obesity (-0.07±0.015) and high WC (-0.048±0.013) were significant (all P<0.001). This association diminished with increasing age. In older participants, TL was inversely related to mortality (hazard ratio 0.36 (0.27, 0.49)), as were those classified by BF1% (0.68 (0.56, 0.81)), BF2% (0.75 (0.65, 0.80)), BMI (0.50 (0.42, 0.60)) and WC (0.72 (0.63, 0.83)). No interaction was observed between adiposity status, telomere length and mortality.ConclusionsObesity is associated with shorter telomere length in young participants, a relationship that diminishes with increasing age. It does not moderate the relationship with mortality.

Project description:BackgroundExposure to persistent organic pollutants (POPs) such as dioxins, furans, and polychlorinated biphenyls (PCBs) may influence leukocyte telomere length (LTL), a biomarker associated with chronic disease. In vitro research suggests dioxins may bind to the aryl hydrocarbon receptor (AhR) and induce telomerase activity, which elongates LTL. However, few epidemiologic studies have investigated associations between POPs and LTL.ObjectivesWe examined the association between 18 PCBs, 7 dioxins, and 9 furans and LTL among 1,330 U.S. adults from NHANES 2001-2002.MethodsWe created three summed POP metrics based on toxic equivalency factor (TEF), a potency measure including affinity for the AhR: a) non-dioxin-like PCBs (composed of 10 non-dioxin-like PCBs; no AhR affinity and no TEF); b) non-ortho PCBs (composed of 2 non-ortho-substituted PCBs with high TEFs); and c) toxic equivalency (TEQ) (composed of 7 dioxins, 9 furans, 2 non-ortho-substituted PCBs, and 6 mono-ortho-substituted PCBs; weighted by TEF). We tested the association between each metric and LTL using linear regression, adjusting for demographics, blood cell count and distribution, and another metric with a different TEF (i.e., non-ortho PCBs and TEQ adjusted for non-dioxin-like PCBs; non-dioxin-like PCBs adjusted for non-ortho PCBs).ResultsIn adjusted models, each doubling of serum concentrations of non-ortho PCBs and TEQ was associated with 3.74% (95% CI: 2.10, 5.40) and 5.29% (95% CI: 1.66, 9.05) longer LTLs, respectively. Compared with the lowest quartile, the highest quartile of exposure was associated with 9.16% (95% CI: 2.96, 15.73) and 7.84% (95% CI: -0.53, 16.92) longer LTLs, respectively. Non-dioxin-like PCBs were not associated with LTL.ConclusionsPOPs with high TEFs and AhR affinity were associated with longer LTL. Because many dioxin-associated cancers are also associated with longer LTL, these results may provide insight into the mechanisms underlying PCB- and dioxin-related carcinogenesis.CitationMitro SD, Birnbaum LS, Needham BL, Zota AR. 2016. Cross-sectional associations between exposure to persistent organic pollutants and leukocyte telomere length among U.S. adults in NHANES, 2001-2002. Environ Health Perspect 124:651-658;?http://dx.doi.org/10.1289/ehp.1510187.

Dataset Information

Urinary Phthalates and Leukocyte Telomere Length: An Analysis of NHANES 1999-2002.

Publications

Urinary Phthalates and Leukocyte Telomere Length: An Analysis of NHANES 1999-2002.

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