Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer.
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.
Wang
Luo
L
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Soria
Jean-Charles
JC
Chang
Yoon-Soo
YS
Lee
Ho-Young
HY
Wei
Qingyi
Q
Mao
Li
L
D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000601:surgery; D017931:DNA Primers; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000601:surgery; D018598:Minisatellite Repeats / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D015347:RNA Probes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020080:Tandem Repeat Sequences / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004268:DNA-Binding Proteins; D015347:RNA Probes; D008156:Luciferases; D019098:Telomerase