title: hTERT cancer risk genotypes are associated with telomere length.
abstract: 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 (hTERT) gene were associated with various malignancies, including glioma, lung and urinary bladder cancer, and telomerase RNA gene hTERC genotypes were recently linked to TL. In the present study a hypothetical association between identified genotypes in hTERT and hTERC genes and TL were investigated. We analyzed 21 polymorphisms, covering 90% of the genetic variance, in the hTERT gene, two genetic variants in hTERC, 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 hTERT gene (rs2736100, rs2853672, rs2853677, and rs2853676), two of which reported to be associated with cancer risk. Two alleles (rs12696304, rs16847897) near the hTERC gene were confirmed as also being associated with RTL at age 60. Our data suggest that hTERT and hTERC 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.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Sweden.
authors.forename: Beatrice S
authors.initials: BS
authors.lastname: Melin
authors.forename: Katarina
authors.initials: K
authors.lastname: Nordfjäll
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012306:Risk; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*
chemical_list: C509186:TERT protein, human; D019098:Telomerase