TY - JOUR
T1 - A functional variant of tandem repeats in human telomerase gene was associated with survival of patients with early stages of non-small cell lung cancer
AU - Wang, Luo
AU - Wang, Li E.
AU - Mao, Li
AU - Spitz, Margaret R.
AU - Wei, Qingyi
PY - 2010/7/15
Y1 - 2010/7/15
N2 - Purpose: Elevated levels of human telomerase (hTERT) mRNA in tumors is a marker for poorer survival in patients with stage I non-small cell lung cancer (NSCLC). A functional variant of MNS16A-short tandem repeats in hTERT (S allele) is associated with higher expression levels of hTERT mRNA compared with the MNS16A-long (L) allele. It is unknown, however, whether or not the hTERT MNS16A variant genotype predicts survival of NSCLC patients. Experimental Design: The hTERT genotypes of 808 patients with NSCLC were determined by direct PCR with genomic DNA. Overall median survival times were estimated by the life-table method, and the log-rank test was used to test for homogeneity of the survival curves. Both univariate and multivariate Cox proportional hazards models were used to assess the associations between survival time and the hTERT genotype as well as other known risk factors. Results: The hTERT variant genotype was not associated with overall survival among the 808 patients. However, among 221 patients with stage I or II NSCLC, the S allele was associated with shorter survival time (P = 0.027, by log-rank test). The adjusted hazard ratios were 1.30 (95% confidence interval, 0.79-2.14; P = 0.310) for the SL-genotype and 2.34 (95% confidence interval, 1.20-4.56, P = 0.012) for the SS-genotype compared with the LL-genotype (P = 0.021 for trend test). These findings were not evident in 587 patients with stage III or IV NSCLC. Conclusion: The functional MNS16A-SS genotype may be a marker for poorer survival in early-stage NSCLC.
AB - Purpose: Elevated levels of human telomerase (hTERT) mRNA in tumors is a marker for poorer survival in patients with stage I non-small cell lung cancer (NSCLC). A functional variant of MNS16A-short tandem repeats in hTERT (S allele) is associated with higher expression levels of hTERT mRNA compared with the MNS16A-long (L) allele. It is unknown, however, whether or not the hTERT MNS16A variant genotype predicts survival of NSCLC patients. Experimental Design: The hTERT genotypes of 808 patients with NSCLC were determined by direct PCR with genomic DNA. Overall median survival times were estimated by the life-table method, and the log-rank test was used to test for homogeneity of the survival curves. Both univariate and multivariate Cox proportional hazards models were used to assess the associations between survival time and the hTERT genotype as well as other known risk factors. Results: The hTERT variant genotype was not associated with overall survival among the 808 patients. However, among 221 patients with stage I or II NSCLC, the S allele was associated with shorter survival time (P = 0.027, by log-rank test). The adjusted hazard ratios were 1.30 (95% confidence interval, 0.79-2.14; P = 0.310) for the SL-genotype and 2.34 (95% confidence interval, 1.20-4.56, P = 0.012) for the SS-genotype compared with the LL-genotype (P = 0.021 for trend test). These findings were not evident in 587 patients with stage III or IV NSCLC. Conclusion: The functional MNS16A-SS genotype may be a marker for poorer survival in early-stage NSCLC.
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U2 - 10.1158/1078-0432.CCR-10-0269
DO - 10.1158/1078-0432.CCR-10-0269
M3 - Article
C2 - 20466886
AN - SCOPUS:77954704732
SN - 1078-0432
VL - 16
SP - 3779
EP - 3785
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -