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h TERT Cancer Risk Genotypes Are Associated With Telomere Length

2012; Wiley; Volume: 36; Issue: 4 Linguagem: Inglês

10.1002/gepi.21630

1098-2272

Beatrice Melin, Katarina Nordfjäll, Ulrika Andersson, Göran Roos,

Nuclear Structure and Function

Telomere biology is associated with cancer initiation and prognosis. Collected data suggest that blood cell telomere length ( TL ) can change over time, which may be related to development of common disorders, such as cardiovascular diseases and cancer. Recently, single nucleotide polymorphisms in the region of the human telomerase reverse transcriptase ( h TERT ) gene were associated with various malignancies, including glioma, lung and urinary bladder cancer, and telomerase RNA gene h TERC genotypes were recently linked to TL . In the present study a hypothetical association between identified genotypes in h TERT and h TERC genes and TL were investigated. We analyzed 21 polymorphisms, covering 90% of the genetic variance, in the h TERT gene, two genetic variants in h TERC , and relative TL ( RTL ) at average age 50 and 60 in 959 individuals with repeated blood samples. Mean RTL at age 60 was associated with four genetic variants of the h TERT gene (rs2736100, rs2853672, rs2853677, and rs2853676), two of which reported to be associated with cancer risk. Two alleles (rs12696304, rs16847897) near the h TERC gene were confirmed as also being associated with RTL at age 60. Our data suggest that h TERT and h TERC genotypes have an impact on TL of potential relevance and detectable first at higher ages, which gives us further insight to the complex regulation of TL . Genet. Epidemiol. 36:368–372, 2012. © 2012 Wiley Periodicals, Inc.