期刊
HUMAN MOLECULAR GENETICS
卷 22, 期 12, 页码 2520-2528出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt086
关键词
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资金
- European Commission [223175 (HEALTH-F2-2009-223175)]
- Cancer Research UK [C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135]
- National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative [1 U19 CA 148537-01]
- Institute of Cancer Research and The Everyman Campaign
- Prostate Action
- Orchid Cancer Appeal
- National Cancer Research Network, UK
- National Cancer Research Institute (NCRI), UK
- NIHR
- Royal Marsden NHS Foundation Trust
- Cancer Research UK [16565, 22310, 16561, 15007, 10118, 11022, 14136] Funding Source: researchfish
- Medical Research Council [G0900871, G1000143, G0401527] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10242, NF-SI-0510-10096] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
- MRC [G0900871] Funding Source: UKRI
Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.
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