Abstract
A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women’s Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8–2.5], and 2.2 [1.2–4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.
Highlights
Telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length
Shorter telomere length has been associated with aging and both shorter and longer telomere length have been associated with risk of a number of chronic diseases [10,11], this heterogeneity may be explained in part by casecontrol vs. prospective cohort study designs
We previously reported that longer telomere length was associated with risk of lung cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) prospective cohort [4], which is comprised of smoking males in Finland
Summary
Telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. The associations between telomere length and cancer risk are inconclusive. Most initial studies used a case-control design and reported that shorter telomere length measured in peripheral white blood cells was associated with increased risk of cancer [1]. Some recent publications using a prospective cohort design have suggested that longer telomere length may be associated with increased risk of certain tumors, including lung, lymphoma, hepatocellular carcinoma, and melanoma [2,3,4,5]. Two case-control studies reported that longer telomere length was associated with colorectal, breast cancer, and breast cancer survival [6,7,8,9]. Several studies have identified a number of polymorphisms that were associated with telomere length [8,14,15,16,17], but a comprehensive understanding of the genetic contribution to telomere length has still not emerged
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