Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
- Fang, J
- Jia, J
- Makowski, M
- Xu, M
- Wang, Z
- Zhang, T
- Hoskins, Jw
- Choi, J
- Han, Y
- Zhang, M
- Thomas, J
- Kovacs, M
- Collins, I
- Dzyadyk, M
- Thompson, A
- O'Neill, M
- Das, S
- Lan, Q
- Koster, R
- Solomon, Rs
- Kraft, P
- Wolpin, Bm
- Jansen, Pwtc
- Olson, S
- Mcglynn, Ka
- Kanetsky, Pa
- Chatterjee, N
- Barrett, Jh
- Dunning, Am
- Taylor, Jc
- Newton Bishop, Ja
- Bishop, Dt
- Andresson, T
- Petersen, Gm
- Amos, Ci
- Iles, Mm
- Nathanson, Kl
- Landi, Mt
- Vermeulen, M
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- Amundadottir, Lt
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- Kooperberg, C
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- Gallinger, S
- Jacobs, Ej
- Kamineni, A
- Van Den Eeden, S
- Klein, Ap
- Kolonel, Ln
- Li, D
- Olson, Sh
- Risch, Ha
- Sesso, Hd
- Visvanathan, K
- Zheng, W
- Albanes, D
- Austin, Ma
- Boutron Ruault, Mc
- Bueno de Mesquita, Hb
- Cotterchio, M
- Gaziano, Jm
- Giovannucci, El
- Goggins, M
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- Mannisto, S
- Patel, Av
- Peeters, Phm
- Riboli, E
- Shu, Xo
- Sund, M
- Thornquist, M
- Tj\uf8nneland, A
- Tobias, Gs
- Trichopoulos, D
- Wactawski Wende, J
- Yu, H
- Yu, K
- Zeleniuch Jacquotte, A
- Hoover, R
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- Chanock, Sj
- Stevens, V
- Albanes, D
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- Mckay, J
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- Mclaughlin, Jr
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- Armstrong, B
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- Holland, E
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- Jenkins, M
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- GHIORZO, PAOLA
- BIANCHI, GIOVANNA
- PASTORINO, LORENZA
- BRUNO, WILLIAM
- ANDREOTTI, VIRGINIA
- Queirolo, P
- SPAGNOLO, FRANCESCO
- Mackie, R
- Lang, J
- Gruis, N
- van Nieuwpoort, Fa
- Out, C
- Bergman, W
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- Helsing, P
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- Cohen Manheim, I
- Laitman, Y
- Harland, M
- Randerson Moor, J
- Laye, J
- Davies, J
- Nsengimana, J
- O'Shea, S
- Chan, M
- Gascoyne, J
- Tucker, Ma
- Goldstein, Am
- Yang, X. r.
DOIAbstract
Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombin...