2014
DOI: 10.1093/hmg/ddu363
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) acros… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

7
126
0

Year Published

2015
2015
2017
2017

Publication Types

Select...
7
1

Relationship

0
8

Authors

Journals

citations
Cited by 89 publications
(133 citation statements)
references
References 88 publications
7
126
0
Order By: Relevance
“…The PanScan III study identified a second independent locus at TERT marked by rs2736098, 10 and further studies have suggested multiple independent risk loci for cancer in this genomic region. 23 26 27 28 Based on the six independent risk loci identified at TERT in a large multicancer analysis by Wang et al, 23 we obtained PanScan genotypes marking these loci for cases and controls from our five cohorts. An SNP at one of the six loci was associated with pancreatic cancer risk to p<0.008 (0.05/6 SNPs), rs2736098 (OR 0.75; 95% CI 0.63 to 0.90; table 4).…”
Section: Resultsmentioning
confidence: 99%
See 2 more Smart Citations
“…The PanScan III study identified a second independent locus at TERT marked by rs2736098, 10 and further studies have suggested multiple independent risk loci for cancer in this genomic region. 23 26 27 28 Based on the six independent risk loci identified at TERT in a large multicancer analysis by Wang et al, 23 we obtained PanScan genotypes marking these loci for cases and controls from our five cohorts. An SNP at one of the six loci was associated with pancreatic cancer risk to p<0.008 (0.05/6 SNPs), rs2736098 (OR 0.75; 95% CI 0.63 to 0.90; table 4).…”
Section: Resultsmentioning
confidence: 99%
“…A second SNP was nominally significant, rs451360 (OR 1.20; 95% CI 1.00 to 1.43); this SNP is known from finemapping analyses to mark the same risk locus as rs401681. 23 We next evaluated the association of the three SNPs related to pancreatic cancer risk with leucocyte telomere length (table 5). rs401681 was statistically significantly associated with leucocyte telomere length in linear regression models ( p=0.023), although power was limited for rs2736098 due to modest overlap between the nested case-control and PanScan populations and lower minor allele frequency.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…The IMPUTE2 program (47) was used to impute genotypes across a 5Mb window on chr13q22.1 (71,425,000-76,425,000 bp (hg19) with a 250 kb buffer on each side as previously described (48). SNPs with low minor allele frequency (MAF < 0.01) or low imputation quality scores (IMPUTE2 information score < 0.3) were removed prior to association analysis.…”
Section: Imputation and Association Analysismentioning
confidence: 99%
“…Up to 90% of human tumours reactivate telomerase, which is epigenetically silenced in most adult somatic cells 1. Somatic promoter mutations and germ-line sequence variants at TERT (the gene that encodes the catalytic subunit of telomerase reverse transcriptase on chr 5p15.33) have been observed in various human cancers, indicating extensive pleiotropy at this locus 3. Although somatic mutations in TERT are uncommon in pancreatic cancer (PC), several independent PC risk loci marked by common (and less common) susceptibility alleles have been (and likely will continue to be) identified at the TERT gene locus 4 5…”
mentioning
confidence: 99%