title: A retrospective examination of mean relative telomere length in the Tasmanian Familial Hematological Malignancies Study.
abstract: Telomere length has a biological link to cancer, with excessive telomere shortening leading to genetic instability and resultant malignant transformation. Telomere length is heritable and genetic variants determining telomere length have been identified. Telomere biology has been implicated in the development of hematological malignancies (HMs), therefore, closer examination of telomere length in HMs may provide further insight into genetic etiology of disease development and support for telomere length as a prognostic factor in HMs. We retrospectively examined mean relative telomere length in the Tasmanian Familial Hematological Malignancies Study using a quantitative PCR method on genomic DNA from peripheral blood samples. Fifty-five familial HM cases, 191 unaffected relatives of familial HM cases and 75 non-familial HM cases were compared with 758 population controls. Variance components modeling was employed to identify factors influencing variation in telomere length. Overall, HM cases had shorter mean relative telomere length (p=2.9×10-6) and this was observed across both familial and non-familial HM cases (p=2.2x10-4 and 2.2x10-5, respectively) as well as additional subgroupings of HM cases according to broad subtypes. Mean relative telomere length was also significantly heritable (62.6%; p=4.7x10-5) in the HM families in the present study. We present new evidence of significantly shorter mean relative telomere length in both familial and non-familial HM cases from the same population adding further support to the potential use of telomere length as a prognostic factor in HMs. Whether telomere shortening is the cause of or the result of HMs is yet to be determined, but as telomere length was found to be highly heritable in our HM families this suggests that genetics driving the variation in telomere length is related to HM disease risk.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Blackburn
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: Jac C
authors.initials: JC
authors.lastname: Charlesworth
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: James R
authors.initials: JR
authors.lastname: Marthick
authors.affiliation: Royal Hobart Hospital, Hobart, TAS 7001, Australia.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Tegg
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Marsden
authors.affiliation: Department of Medicine, Monash Medical Centre, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3168, Australia.
authors.forename: Velandai
authors.initials: V
authors.lastname: Srikanth
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78245-0549, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: Ray M
authors.initials: RM
authors.lastname: Lowenthal
authors.affiliation: John Curtain School of Medical Research, Australian National University, ACT 2601, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foote
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Dickinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013648:Tasmania; D059506:Telomere Shortening; D055815:Young Adult