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Telomeres are nucleoprotein complexes composed of non‐coding TTAGGG repeats and associated telomere binding proteins. The main function of telomeres is to cap the ends of chromosomes and to protect chromosomes from degradation, end‐to‐end fusion and atypical recombination.(1) Telomeres are approximately 10–15 kb in human somatic cells, and they shorten by 50–200 bp with each cell division,(2) primarily as a result of incomplete replication of linear chromosomes by conventional DNA polymerases (known as the end replication problem).(3–5) This progressive shortening of the telomere limits the replicative capacity of human somatic cells to 50–80 cell divisions and serves as a ‘mitotic clock’ that defines the lifespan of somatic cells.(6,7) When the telomeres reach a critical length, cells undergo either irreversible growth arrest, called cellular senescence, or apoptosis.(8,9)
In addition to the role of telomere shortening in organismal aging, it has been proposed that short telomeres suppress tumor formation by limiting the proliferation of transformed cells.(8,10,11) However, in contrast to this hypothesis, it has also been reported that cancer risk sharply increases in response to telomere shortening during aging and chronic illness.(12) Moreover, several studies have demonstrated that cancer cells have shorter telomeres than the surrounding non‐malignant cells.(13,14) Additionally, studies of telomerase knockout mice found that telomere shortening induces chromosome instability, which is perpetuated through fusion–bridge–breakage cycles that increase the risk of cancer development.(15–18)
Several studies have documented considerable variation in the length of telomeres of peripheral blood lymphocytes among normal individuals of the same age.(19–21) In addition, a few case‐control studies have observed that individuals with shorter telomeres are at an increased risk for the development of human cancers.(22–24) To further verify the role of the telomere length on the risk of lung cancer, we investigated the association between telomere length and lung cancer risk in a case‐control study.
Study population. This case‐control study included 243 lung cancer cases and 243 healthy controls. Detailed description of subject enrollment has been published.(25,26) Briefly, the cases were newly diagnosed with primary lung cancer between January 2005 and July 2005...