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Telomere length variation: A potential new telomere biomarker for lung cancer risk.

ABSTRACT: In this report the associations between telomere length variation (TLV), mean telomere length in blood lymphocytes and lung cancer risk were examined.The study design is case-control. Cases (N=191) were patients newly diagnosed with histologically confirmed non-small cell lung cancer. Controls (N=207) were healthy individuals recruited from the same counties as cases and matched to cases on age and gender. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and lung cancer risk.Telomere length variation across all chromosomal ends was significantly associated with lung cancer risk; adjusted odds ratios 4.67 [95% confidence interval (CI): 1.46-14.9] and 0.46 (95% CI: 0.25-0.84) for younger (age?60) and older (age>60) individuals, respectively. TLV and mean telomere length jointly affected lung cancer risk: when comparing individuals with short telomere length and high TLV to those with long telomere length and low TLV, adjusted odd ratios were 8.21 (95% CI: 1.71-39.5) and 0.33 (95% CI: 0.15-0.72) for younger and older individuals, respectively.TLV in blood lymphocytes is significantly associated with lung cancer risk and the associations were modulated by age. TLV in combination with mean telomere length might be useful in identifying high risk population for lung cancer computerized tomography screening.

SUBMITTER: Sun B

PROVIDER: S-EPMC4428929 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Telomere length variation: A potential new telomere biomarker for lung cancer risk.

Sun Bing B Wang Ying Y Kota Krishna K Shi Yaru Y Motlak Salaam S Makambi Kepher K Loffredo Christopher A CA Shields Peter G PG Yang Qin Q Harris Curtis C CC Zheng Yun-Ling YL

Lung cancer (Amsterdam, Netherlands) 20150320 3

<h4>Objectives</h4>In this report the associations between telomere length variation (TLV), mean telomere length in blood lymphocytes and lung cancer risk were examined.<h4>Materials and methods</h4>The study design is case-control. Cases (N=191) were patients newly diagnosed with histologically confirmed non-small cell lung cancer. Controls (N=207) were healthy individuals recruited from the same counties as cases and matched to cases on age and gender. Telomere fluorescent in situ hybridizatio ...[more]

PMID: 25840848

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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.

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Telomere length variation: A potential new telomere biomarker for lung cancer risk.

Publications

Telomere length variation: A potential new telomere biomarker for lung cancer risk.

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