Genetic Variants in Human Telomerase, Telomere Length and Lung, Prostate and Colorectal Cancer Susceptibility

Telomeres form the distal parts of eukaryotic chromosomes and protect chromosomal ends from degradation and end-to-end fusion. Human telomerase reverse transcriptase (TERT) gene encodes a ribonucleoprotein enzyme that is able to extend chromosome ends that have been shortened during successive cycles of cell division. Genome-wide association studies (GWAS) associated 5p15.33, the genomic region harboring TERT, with susceptibility to several cancers, supporting the important role of telomerase in carcinogenesis.

Because genetic variation in TERT and its regulatory elements may influence cancer susceptibility, we have investigated single nucleotide polymorphisms (SNPs) in TERT as well as a polymorphic tandem repeats minisatellite of TERT termed MNS16A. We found significant associations of MNS16A variable number of tandem repeats (VNTRs) in association with colorectal cancer as well as prostate cancer. We have identified two novel variants of MNS16A, namely VNTR-364 and VNTR-212 in addition to the four previously reported VNTRs and are under way to investigate the functionality of these variants. Furthermore, we intend to determine telomere length in our three cohorts using a quantitative PCR assay for measurement of telomere length and their association with genetic variants.We aim to broadly characterize the TERT-CLPTM1L region in regard of common SNPs and minisatellites in order to assess their relevance for cancer etiology and to elucidate the functional mechanisms underlying the associations of TERT polymorphisms with cancer.