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    hTERT promoter polymorphism, -1327C\u3eT, is associated with the risk of epithelial cancer

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    Telomeres are repetitive nucleotide sequences that cap the end of eukaryotic chromosomes. Attrition of these structures has been associated with carcinogenesis in many tissues, and therefore, they are essential for chromosome stabilization. Telomeres are maintained by telomerase complexes, of which human telomerase reverse transcriptase (hTERT) is an essential component. A functional polymorphism, -1327C\u3eT (rs2735940), located in the promoter of the hTERT gene is associated with telomere length in peripheral blood leukocytes. We hypothesized that this polymorphism might affect susceptibility to various epithelial malignancies. The -1327C\u3eT polymorphism was examined in 1,551 consecutive autopsy cases (mean age, 80.3 years), and we focused on its effect on the risks of overall and each primary malignancies. The polymorphism was further studied in 391 clinical prostate cancer patients who were diagnosed via prostate biopsy, using autopsy cases as controls. In the autopsy cases, the risk of epithelial malignancy, after adjusting for age, sex, smoking, and drinking habits, was significantly lower for the TT genotype than the CC (reference) genotype (adjusted odds ratio = 0.61, 95% CI = 0.42-0.90). Among primary malignancies, latent prostate cancer, colorectal cancer, and lung cancer were the most strongly associated with the polymorphism. In the study using clinical prostate cancer patients, susceptibility to clinical prostate cancer was lower for -1327 T carriers than for -1327 T non-carriers, but this finding was not significant. The data suggest that the hTERT promoter polymorphism, -1327C\u3eT, is an independent factor influencing the risk of various epithelial malignancies in elderly Japanese
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