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

Document Type: Research Articles

Authors

1 Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

2 Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University,Fukuoka,Japan.

3 Kirigaoka Tsuda Hospital, Fukuoka, Japan.

4 Division of Respiratory Medicine, National Hospital Organization, Fukuoka Higashi Medical Center, Fukuoka, Japan

5 Division of Respiratory Medicine, Kyushu Rosai Hospital, Fukuoka, Japan

6 Department of Respiratory Medicine, Fukuoka University Chikushi Hospital, Fukuoka, Japan

7 Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Fukuoka, Japan

8 Department of Respiratory Medicine, Wakamatsu Hospital of the University of Occupational and Environmental Health, Japan, Fukuoka, Japan

9 Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan

10 Department of Respiratory Medicine, Fukuoka University School of Medicine, Fukuoka, Japan

Abstract

Background: Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis.  Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases.  As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study. Materials and Methods: A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study.  Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals. Results: TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008).  Similarly, TERT rs2736100 was associated with the risk of COPD.  In regard to the combined action of the three loci, increasing numbers of “at-risk” genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003). Conclusions: TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the “at-risk” genotypes might be important to identify the population at risk for IPF more clearly.

Keywords

Main Subjects