title: The relationship between telomere length and mortality in chronic obstructive pulmonary disease (COPD).
abstract: Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS). The subjects were followed for approximately 7.5 years during which time their vital status, FEV(1) and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy "mid-life" volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy "mid-life" volunteers (p<.001). Compared to individuals in the 4(th) quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324) and total mortality (HR, 1.29; p = 0.0425). Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD.
authors.affiliation: The Providence Heart and Lung Institute at St. Paul's Hospital, The UBC James Hogg Research Centre & Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jee
authors.initials: J
authors.lastname: Lee
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
authors.forename: John E
authors.initials: JE
authors.lastname: Connett
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.forename: Tammy
authors.initials: T
authors.lastname: Mui
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Li
authors.forename: Denise
authors.initials: D
authors.lastname: Daley
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Anthonisen
authors.forename: Angela
authors.initials: A
authors.lastname: Brooks-Wilson
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000235:genetics* / Q000401:mortality; D012129:Respiratory Function Tests; D012307:Risk Factors; D012907:Smoking; D016019:Survival Analysis; D016615:Telomere / Q000737:chemistry / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics