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Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer

Oncogene volume 22, pages 7123–7129 (2003)Cite this article

Abstract

Chemoprevention has been widely explored as a promising strategy for controlling the incidence of lung cancer, the leading cause of cancer-related death. To maximize the benefit of lung cancer chemoprevention, it is important to identify individuals at high risk for the disease. The genetic background has been shown to play an important role in one's risk of developing lung cancer. We report here the identification of a polymorphic tandem repeats minisatellite (termed MNS16A) in the downstream region of the human telomerase gene. This minisatellite is located upstream of an antisense transcript from the human telomerase gene locus and was demonstrated to have promoter activity. The promoter activity was significantly lower in the construct containing the shorter repeats, suggesting that the MNS16A variant may have a relevance of functionality. To explore the role of this novel polymorphism in lung cancer, we conducted a pilot hospital-based case–control study by identifying the MNS16A genotype with genomic DNA from 53 lung cancer patients and 72 cancer-free controls. We found four different alleles and classified them as shorter (S) or longer (L) on the functional basis of the length of the repeats in the controls. The MNS16A genotype distributions of the SS, SL, and LL genotypes were 11, 32, and 57%, respectively, in the cases, and 14, 40, and 46%, respectively, in the controls. Compared with the SS+SL genotype, the LL genotype was associated with greater than twofold increased risk of lung cancer (odds ratio=2.18; 95% confidence interval=0.92, 5.20) after adjustment for age, sex, ethnicity, and smoking status, suggesting a potential role of MNS16A in lung cancer susceptibility. Larger studies are needed to verify our findings.

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Acknowledgements

This work was supported in part by Grant DAMD17-01-1-0689-1 from the Department of Defense and Grants PO1 CA91844, P30 CA16620, and U01 CA 86390 from the National Cancer Institute, USA. We thank Stephanis Deming for editing the manuscript and patient population identified through a search of the tumor registry database maintained by the Department of Medical Informatics.

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  1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    Luo Wang, Jean-Charles Soria, Yoon-Soo Chang, Ho-Young Lee & Li Mao

  2. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    Qingyi Wei

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  1. Luo Wang
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Correspondence to Li Mao.

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Wang, L., Soria, JC., Chang, YS. et al. Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer. Oncogene 22, 7123–7129 (2003). https://doi.org/10.1038/sj.onc.1206852

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