Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Cardiac chamber volumes and left ventricular mass in people living with HIV and matched uninfected controls

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. MicroRNA Biomarkers in IBD-Differential Diagnosis and Prediction of Colitis-Associated Cancer

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

Vis graf over relationer
TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind45
Udgave nummer4
Sider (fra-til)371-84, 384e1-2
ISSN1061-4036
DOI
StatusUdgivet - apr. 2013

ID: 38625454