Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
書誌事項
- 公開日
- 2013-03-27
- 資源種別
- journal article
- 権利情報
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- http://www.springer.com/tdm
- DOI
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- 10.1038/ng.2566
- 10.13025/24940
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 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 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 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 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 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.
収録刊行物
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- Nature Genetics
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Nature Genetics 45 (4), 371-384, 2013-03-27
Springer Science and Business Media LLC
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キーワード
- Genetic-variation
- Càncer d'ovari
- Breast cancer
- ONCOL 1: Hereditary cancer and cancer-related syndromes
- common variants
- Aetiology
- Tumor Markers
- Gene Environment Interaction and Breast Cancer
- Cancer
- Oligonucleotide Array Sequence Analysis
- Ovarian Neoplasms
- Non-P.H.S
- Tumor
- Telòmer
- COMMON VARIANTS
- tert-clptm1l locus; genome-wide association; genetic-variation; susceptibility loci; buccal cells; fibroblasts; common variants; carcinoma; reverse-transcriptase htert; metaanalysis
- Telomere
- Chromatin
- Tumor Markers, Biological
- genetic-variation
- Hereditary Breast and Ovarian Cancer Research Group Netherlands
- 570
- FIBROBLASTS
- CARCINOMA
- Genotype
- ONCOL 3: Translational research IGMD 3: Genomic disorders and inherited multi-system disorders
- 610
- TERT-CLPTM1L locus
- 1311 Genetics
- SDG 3 - Good Health and Well-being
- Ovarian cancer
- Australian Cancer Study
- 616
- Genetics
- Humans
- RNA, Messenger
- Polymorphism
- GENOME-WIDE ASSOCIATION
- METAANALYSIS
- tert-clptm1l locus
- Reverse-transcriptase hTERT
- Common variants
- Prevention
- Buccal Cells
- Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer
- Fibroblasts
- DNA Methylation
- Biological
- ONCOL 5: Aetiology, screening and detection
- TERT-CLPTM1L LOCUS
- susceptibility loci
- name=SDG 3 - Good Health and Well-being
- Alternative Splicing
- ONCOL 3: Translational research
- Genetic Loci
- Case-Control Studies
- U.S. Gov't
- ONCOL 5: Aetiology, screening and detection NCMLS 2: Immune Regulation
- EMC MM-03-86-01
- Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers
- Biomarkers
- Developmental Biology
- buccal cells
- Swedish Breast Cancer Study
- Messenger
- Australian Ovarian Cancer Study
- carcinoma
- Medical and Health Sciences
- Risk Factors
- Alternative Splicing; Biomarkers, Tumor; Breast Neoplasms; Case-Control Studies; Chromatin; DNA Methylation; Female; Gene Expression Profiling; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Luciferases; Oligonucleotide Array Sequence Analysis; Ovarian Neoplasms; Polymorphism, Single Nucleotide; RNA, Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Telomerase; Telomere; Genetics
- 2.1 Biological and endogenous factors
- BUCCAL CELLS
- Non-U.S. Gov't
- Luciferases
- Telomerase
- EMC MGC-02-96-01
- Genome-wide association
- Reverse Transcriptase Polymerase Chain Reaction
- GENETIC-VARIATION
- Single Nucleotide
- Metaanalysis
- Biological Sciences
- Ovarian Cancer
- RG Gynecology and obstetrics
- /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
- Female
- reverse-transcriptase htert
- metaanalysis
- NCEBP 1: Molecular epidemiology ONCOL 5: Aetiology, screening and detection
- SUSCEPTIBILITY LOCI
- Breast Neoplasms
- R Medicine
- Research Support
- Real-Time Polymerase Chain Reaction
- Polymorphism, Single Nucleotide
- N.I.H.
- Càncer de mama
- Rare Diseases
- fibroblasts
- Breast Cancer
- Journal Article
- Biomarkers, Tumor
- Genetic Predisposition to Disease
- Epidemiological study of BRCA1 & BRCA2 Mutation Carriers
- Gene Expression Profiling
- Carcinoma
- Extramural
- genome-wide association
- RNA
- Susceptibility loci
- REVERSE-TRANSCRIPTASE HTERT
- Genome-Wide Association Study
詳細情報 詳細情報について
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- CRID
- 1360846641736478208
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- ISSN
- 15461718
- 10614036
- https://id.crossref.org/issn/10614036
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- PubMed
- 23535731
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- 資料種別
- journal article
-
- データソース種別
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- Crossref
- KAKEN
- OpenAIRE