Krauskopf, A. &
Telomeres and their control. Annu. Rev. Genet.
34, 331–358 (2000).
Palm, W. & de Lange, T.
How shelterin protects mammalian telomeres. Annu. Rev. Genet.
42, 301–334 (2008).
Telomeres. Exp. Gerontol.
41, 1223–1227 (2006).
et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl. Acad. Sci. USA
85, 6622–6626 (1988).
et al. Telomere length predicts replicative capacity of human fibroblasts. Proc. Natl. Acad. Sci. USA
89, 10114–10118 (1992).
Telomere loss: mitotic clock or genetic time bomb?
256, 271–282 (1991).
et al. Telomere end-replication problem and cell aging.
J. Mol. Biol.
225, 951–960 (1992).
et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
11, 1921–1929 (1992).
et al. Telomerase activity in human breast tumors. J. Natl. Cancer Inst.
88, 116–122 (1996).
Stampfer, M.R. &
Human epithelial cell immortalization as a step in carcinogenesis.
194, 199–208 (2003).
et al. Telomere length is associated with disease severity and declines with age in dyskeratosis congenita. Haematologica
97, 353–359 (2012).
et al. Telomere length is paternally inherited and is associated with parental lifespan. Proc. Natl. Acad. Sci. USA
104, 12135–12139 (2007).
Droog, S. &
Genetic determination of telomere size in humans: a twin study of three age groups. Am. J. Hum. Genet.
55, 876–882 (1994).
et al. The association of telomere length and genetic variation in telomere biology genes. Hum. Mutat.
31, 1050–1058 (2010).
et al. No association between TERT-CLPTM1L single nucleotide polymorphism rs401681 and mean telomere length or cancer risk. Cancer Epidemiol. Biomarkers Prev.
19, 1862–1865 (2010).
et al. Telomerase reverse transcriptase locus polymorphisms and cancer risk: a field synopsis and meta-analysis. J. Natl. Cancer Inst.
104, 840–854 (2012).
et al. Genetic variation in TERT and TERC and human leukocyte telomere length and longevity: a cross-sectional and longitudinal analysis. Aging Cell
11, 223–227 (2012).
et al. Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiol. Biomarkers Prev.
16, 815–819 (2007).
et al. Telomere length in prospective and retrospective cancer case-control studies. Cancer Res.
70, 3170–3176 (2010).
et al. Telomere length, oxidative damage, antioxidants and breast cancer risk. Int. J. Cancer
124, 1637–1643 (2009).
et al. The association of telomere length and cancer: a meta-analysis. Cancer Epidemiol. Biomarkers Prev.
20, 1238–1250 (2011).
De Vivo, I.
et al. A prospective study of relative telomere length and postmenopausal breast cancer risk. Cancer Epidemiol. Biomarkers Prev.
18, 1152–1156 (2009).
et al. Mean telomere length and risk of incident colorectal carcinoma: a prospective, nested case-control approach. Cancer Epidemiol. Biomarkers Prev.
18, 2280–2282 (2009).
Variation at the TERT locus and predisposition for cancer.
Expert Rev. Mol. Med.
12, e16 (2010).
et al. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers.
6, e24987 (2011).
et al. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat. Genet.
43, 785–791 (2011).
et al. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.
Am. J. Hum. Genet.
85, 679–691 (2009).
et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat. Genet.
41, 221–227 (2009).
et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat. Genet.
41, 899–904 (2009).
et al. New common variants affecting susceptibility to basal cell carcinoma. Nat. Genet.
41, 909–914 (2009).
et al. Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat. Genet.
42, 604–607 (2010).
et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat. Genet.
40, 1407–1409 (2008).
et al. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and
TERT, a cancer susceptibility “hot-spot”.
6, e1001016 (2010).
et al. A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer.
43, 1210–1214 (2011).
1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature
467, 1061–1073 (2010).
et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat. Genet. published online; doi:10.1038/ng.2563 (27 March 2013).
et al. GWAS meta-analysis and replication identifies three new common susceptibility loci for ovarian cancer. Nat. Genet. published online; doi:10.1038/ng.2564 (27 March 2013).
et al. Genome-wide association studies identify four ER negative–specific breast cancer risk loci. Nat. Genet. published online; doi:10.1038/ng.2561 (27 March 2013).
et al. ENCODE whole-genome data in the UCSC Genome Browser: update 2012. Nucleic Acids Res.
40, D912–D917 (2012).
et al. FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin.
17, 877–885 (2007).
et al. ESPERR: learning strong and weak signals in genomic sequence alignments to identify functional elements. Genome Res.
16, 1596–1604 (2006).
et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat. Med.
15, 907–913 (2009).
et al. PAX8 regulates telomerase reverse transcriptase and telomerase RNA component in glioma. Cancer Res.
68, 5724–5732 (2008).
et al. The hTERTα splice variant is a dominant negative inhibitor of telomerase activity. Neoplasia
2, 426–432 (2000).
Fossberg, E. &
Characterization of novel alternative splicing sites in human telomerase reverse transcriptase (hTERT): analysis of expression and mutual correlation in mRNA isoforms from normal and tumour tissues. BMC Mol. Biol.
7, 26 (2006).
et al. Isolation of a candidate human telomerase catalytic subunit gene, which reveals complex splicing patterns in different cell types.
Hum. Mol. Genet.
6, 2011–2019 (1997).
Wick, M., Zubov, D. & Hagen, G.
Genomic organization and promoter characterization of the gene encoding the human telomerase reverse transcriptase (hTERT). Gene
232, 97–106 (1999).
et al. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res.
37, e67 (2009).
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature
474, 609–615 (2011).
et al. Short telomere length, myocardial infarction, ischemic heart disease, and early death. Arterioscler. Thromb. Vasc. Biol.
32, 822–829 (2012).
et al. Common variants near TERC are associated with mean telomere length. Nat. Genet.
42, 197–199 (2010).
et al. Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proc. Natl. Acad. Sci. USA
107, 9293–9298 (2010).
et al. Telomere length and risk of incident cancer and cancer mortality. J. Am. Med. Assoc.
304, 69–75 (2010).
et al. Fine-mapping identifies multiple prostate cancer risk loci on 5p15, one of which associates with TERT expression. Hum. Mol. Genet. published online; doi:10.1093/hmg/ddt086 (27 March 2013).
et al. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc. Natl. Acad. Sci. USA
98, 12072–12077 (2001).
et al. Senescent fibroblasts promote neoplastic transformation of partially transformed ovarian epithelial cells in a three-dimensional model of early stage ovarian cancer. Neoplasia
12, 317–325 (2010).
et al. Lung cancer susceptibility locus at 5p15.33. Nat. Genet.
40, 1404–1406 (2008).
et al. Multiple genetic variants in telomere pathway genes and breast cancer risk. Cancer Epidemiol. Biomarkers Prev.
19, 219–228 (2010).
et al. A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese.
43, 792–796 (2011).
et al. A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J. Med. Genet.
45, 654–656 (2008).
et al. Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium. J. Natl. Cancer Inst.
102, 959–971 (2010).
et al. The TERT rs2736100 polymorphism and cancer risk: a meta-analysis based on 25 case-control studies. BMC Cancer
12, 7 (2012).
et al. Fine-mapping of a region of chromosome 5p15.33 (TERT-CLPTM1L) suggests a novel locus in TERT and a
CLPTM1L haplotype are associated with glioma susceptibility in a Chinese population. Int. J. Cancer
129, 2463–2472 (2011).
et al. Telomere lengths are characteristic in each human individual. Exp. Gerontol.
37, 523–531 (2002).
et al. Telomere length in blood, buccal cells, and fibroblasts from patients with inherited bone marrow failure syndromes. Aging (Albany. NY)
2, 867–874 (2010).
Thomas, P., O' Callaghan, N.J. &
Telomere length in white blood cells, buccal cells and brain tissue and its variation with ageing and Alzheimer's disease. Mech. Ageing Dev.
129, 183–190 (2008).
Greider, C.W. &
Identification of a specific telomere terminal transferase activity in
Tetrahymena extracts. Cell
43, 405–413 (1985).
et al. TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program. PLoS Genet.
4, e10 (2008).
et al. Telomerase modulates Wnt signalling by association with target gene chromatin. Nature
460, 66–72 (2009).
et al. Separation of telomerase functions by reverse genetics.
Proc. Natl. Acad. Sci. USA
108, E1363–E1371 (2011).
et al. Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk. PLoS Genet.
9, e1003173 (2013).
et al. Association between a germline OCA2 polymorphism at chromosome 15q13.1 and estrogen receptor–negative breast cancer survival. J. Natl. Cancer Inst.
102, 650–662 (2010).
Tybjaerg-Hansen, A. &
Integrin β3 Leu33Pro homozygosity and risk of cancer.
J. Natl. Cancer Inst.
95, 1150–1157 (2003).
Allin, K.H., Bojesen, S.E. & Nordestgaard, B.G.
Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J. Clin. Oncol.
27, 2217–2224 (2009).
et al. C-reactive protein and the risk of cancer: a mendelian randomization study. J. Natl. Cancer Inst.
102, 202–206 (2010).
et al. Genetically elevated C-reactive protein and ischemic vascular disease. N. Engl. J. Med.
359, 1897–1908 (2008).
et al. Estimating local ancestry in admixed populations.
Am. J. Hum. Genet.
82, 290–303 (2008).
et al. Telomere length and genetic variation in telomere maintenance genes in relation to ovarian cancer risk. Cancer Epidemiol. Biomarkers Prev.
21, 504–512 (2012).
Telomere measurement by quantitative PCR. Nucleic Acids Res.
30, e47 (2002).
Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res.
37, e21 (2009).
et al. Evaluation of association methods for analysing modifiers of disease risk in carriers of high-risk mutations. Genet. Epidemiol.
36, 274–291 (2012).
et al. A locus on 19p13 modifies risk of breast cancer in
BRCA1 mutation carriers and is associated with hormone receptor–negative breast cancer in the general population.
42, 885–892 (2010).
et al. A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes.
29, 1–11 (2005).
et al. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability. Nat. Med.
14, 1384–1389 (2008).