Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/98570
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Type: Journal article
Title: Candidate locus analysis of the TERT–CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk
Author: Carvajal-Carmona, L.
O Mara, T.
Painter, J.
Lose, F.
Dennis, J.
Michailidou, K.
Tyrer, J.
Ahmed, S.
Ferguson, K.
Healey, C.
Pooley, K.
Beesley, J.
Cheng, T.
Jones, A.
Howarth, K.
Martin, L.
Gorman, M.
Hodgson, S.
National Study of Endometrial Cancer Genetics Group (NSECG),
The Australian National Endometrial Cancer Study Group (ANECS)
et al.
Citation: Human Genetics, 2015; 134(2):231-245
Publisher: Springer-Verlag
Issue Date: 2015
ISSN: 0340-6717
1432-1203
Statement of
Responsibility: 
Luis G. Carvajal‑Carmona ... National Study of Endometrial Cancer Genetics Group (NSECG) ... The Australian National Endometrial Cancer Study Group (ANECS) ... RENDOCAS ... Australian Ovarian Cancer Study (AOCS) ... The GENICA Network ... et al.
Abstract: Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT-CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk (P = 4.9 × 10(-6) to P = 7.7 × 10(-5)). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERT P = 1.5 × 10(-18), CLPTM1L P = 1.5 × 10(-19)). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.
Keywords: Humans
Description: Published online: 9 December 2014
Rights: © The Author(s) 2014 Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
RMID: 0030037557
DOI: 10.1007/s00439-014-1515-4
Grant ID: http://purl.org/au-research/grants/nhmrc/1031333
http://purl.org/au-research/grants/nhmrc/339435
http://purl.org/au-research/grants/nhmrc/1031333
Appears in Collections:Medicine publications

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