Association between Telomere-Related Polymorphisms and the Risk of IPF and COPD as a Precursor Lesion of Lung Cancer: Findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) Registry

Arimura-Omori, Masako; Kiyohara, Chikako; Yanagihara, Toyoshi; Yamamoto, Yūzō; Ogata-Suetsugu, Saiko; Harada, Eiji; Hamada, Naoki; Tsuda, Toru; Takata, Shohei; Shimabukuro, Ikuko; Nagata, Nobuhiko; Yatera, Kazuhiro; Torii, Ryo; Okamoto, Masaki; Fujita, Masaki; Nakanishi, Yoichi

doi:10.31557/apjcp.2020.21.3.667

Cited by 10 publications

(10 citation statements)

References 47 publications

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“…Our results are in agreement with previous studies indicating that carriers of two reference rs2736100 C alleles generally have a higher risk of developing idiopathic lung fibrosis, chronical obstructive pulmonary disease (COPD) and laryngeal cancer. 18 , 39 , 40 …”

Section: Discussionmentioning

confidence: 99%

Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

Mervic,

Goricar,

Blagus

et al. 2024

Radiology and Oncology

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Background Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM). Subjects and methods We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis. Results Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038). Conclusions Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.

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Section: Discussionmentioning

confidence: 99%

Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

Mervic,

Goricar,

Blagus

et al. 2024

Radiology and Oncology

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“…Up to one-third of people with FPF have TS and carry a telomere-related mutation; regardless of the IPF phenotype, individuals with TS and telomere-related mutations have more rapid disease progression [ 140 , 141 , 142 ]. In fact, reports show that TS is associated with susceptibility to IPF [ 75 , 143 , 144 ].…”

Section: Immunotherapy Pharmacology and Genetic Therapymentioning

confidence: 99%

Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

Ruíz

Flores‐González

Buendía-Roldán

et al. 2021

IJMS

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Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.

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“…TaqMan ® SNP Genotyping Assays purchased from Applied Biosystems (Foster City, CA, USA) were used for the following [gene, single nucleotide polymorphism (SNP), assay ID]: TERT, rs2736100, C___1844009_10; TERC, rs1881984, C____176429_10; and OBFC1, rs11191865, C___2818536_10. The real-time PCR reaction conditions used are described in Arimura-Omori (2020). For quality control, we repeated assays on a random 5% of all samples, and the replicates were 100% concordant.…”

Section: Genetic Analysismentioning

confidence: 99%

The Association of Aging-Related Polymorphisms with Susceptibility to Lung Cancer: A Case-Control Study in a Japanese Population

Furuie

Arimura-Omori

Hamada

et al. 2021

Asian Pac J Cancer Prev

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Background: Telomere length is associated with cancer as well as aging. Telomerase reverse transcriptase (TERT), telomere RNA component (TERC) and oligonucleotide/oligosaccharide-binding fold containing 1 (OBFC1) are known to be involved in telomere length regulation. The tumor suppressor p53 (TP53), which has been shown to interact with tumor protein p53-binding protein 1 (TP53BP1), is implicated in the response to telomere shortening and aging. Polymorphisms in the TP53 and TP53BP1 genes are associated with various types of cancer. The aim of this study is to evaluate the impact of aging-related polymorphisms on lung cancer risk. Materials and Methods: This case-control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of TERT rs2736100, TERC rs1881984, OBFC1 rs11191865, TP53 rs1042522 and TP53BP1 rs560191 on the risk of lung cancer using a Taq-Man real-time PCR assay. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: None of the main effects of any of the telomere-related polymorphisms were related to the risk of lung cancer. Similarly, none of the interactive effects of any of the telomere-related polymorphisms with smoking were associated with lung cancer risk. The significant multiplicative interaction between TERT rs2736100 and TP53BP1 rs560191 was statistically significant (OR for interaction = 0.34, 95% CI = 0.14-0.84). The multiplicative interaction between OBFC1 rs11191865 and TP53BP1 rs560191 was also statistically significant (OR for interaction = 2.44, 95% CI = 1.02-5.87) but the OR for interaction was in the opposite direction. Conclusions: Our findings indicate that TP53BP1 rs560191 may predispose to lung cancer risk depending on the genotypes of telomere-related polymorphisms. Additional studies are warranted to confirm the findings suggested in the present study.

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Association between Telomere-Related Polymorphisms and the Risk of IPF and COPD as a Precursor Lesion of Lung Cancer: Findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) Registry

Cited by 10 publications

References 47 publications

Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

The Association of Aging-Related Polymorphisms with Susceptibility to Lung Cancer: A Case-Control Study in a Japanese Population

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