Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Ünal, Pelin; Morelli, Luca; Canzian, Federico; Gazouli, Maria; Uzunoglu, Faik G; Capurso, Gabriele; Milanetto, Anna Caterina; Palmieri, Orazio; Perri, Francesco; Maiello, Evaristo; Dijk, Frederike; Vokacova, Klara; Arcidiacono, Paolo Giorgio; Soucek, Pavel; Oliverius, Martin; Ermini, Stefano; Włodarczyk, Barbara; Kupcinskas, Juozas; Izbicki, Jakob R; Carrara, Silvia; Hlavac, Viktor; Kiudelis, Vytautas; Pasquali, Claudio; Erőss, Bálint; Capretti, Giovanni; Lu, Ye; Mohelnikova-Duchonova, Beatrice; Bambi, Franco; Landi, Stefano; Kondrackiene, Jurate; van Eijck, Casper H J; Giaccherini, Matteo; Archibugi, Livia; Theodoropoulos, George E; Sperti, Cosimo; Szentesi, Andrea; Lawlor, Rita T; Vanella, Giuseppe; Bueno-de-Mesquita, Bas; Brenner, Hermann; Stocker, Hannah; Gentiluomo, Manuel; Bunduc, Stefania; Di Franco, Gregorio; Pezzilli, Raffaele; Chammas, Roger; Basso, Daniela; Testoni, Sabrina Gloria Giulia; Neoptolemos, John P; Małecka-Wojciesko, Ewa; Talar-Wojnarowska, Renata; Hegyi, Péter; Bazzocchi, Francesca; Nóbrega Aoki, Mateus; Kreivenaite, Edita; Cavestro, Giulia Martina; Bijlsma, Maarten F; Schöttker, Ben; Petrone, Maria Chiara; Campa, Daniele; Boggi, Ugo; Hackert, Thilo; Vodickova, Ludmila; Goetz, Mara; Tavano, Francesca

doi:10.1186/s40246-024-00576-x

Items
Marc 21

001			287622
005			20250415112709.0
024	7	_	\|a 10.1186/s40246-024-00576-x \|2 doi
024	7	_	\|a pmid:38308339 \|2 pmid
024	7	_	\|a 1473-9542 \|2 ISSN
024	7	_	\|a 1479-7364 \|2 ISSN
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037	_	_	\|a DKFZ-2024-00276
041	_	_	\|a English
082	_	_	\|a 570
100	1	_	\|a Ünal, Pelin \|0 P:(DE-He78)0149ac455a0174a847bd30162edf897b \|b 0 \|e First author \|u dkfz
245	_	_	\|a Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.
260	_	_	\|a London [u.a.] \|c 2024 \|b Henry Stewart Publ.
336	7	_	\|a article \|2 DRIVER
336	7	_	\|a Output Types/Journal article \|2 DataCite
336	7	_	\|a Journal Article \|b journal \|m journal \|0 PUB:(DE-HGF)16 \|s 1707140221_27093 \|2 PUB:(DE-HGF)
336	7	_	\|a ARTICLE \|2 BibTeX
336	7	_	\|a JOURNAL_ARTICLE \|2 ORCID
336	7	_	\|a Journal Article \|0 0 \|2 EndNote
500	_	_	\|a #EA:C055#LA:C055#
520	_	_	\|a Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.
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650	_	7	\|a Association study \|2 Other
650	_	7	\|a Enhancer \|2 Other
650	_	7	\|a Pancreatic cancer \|2 Other
650	_	7	\|a Single nucleotide polymorphism \|2 Other
650	_	7	\|a Transcription factor binding site \|2 Other
700	1	_	\|a Lu, Ye \|b 1
700	1	_	\|a Bueno-de-Mesquita, Bas \|b 2
700	1	_	\|a van Eijck, Casper H J \|b 3
700	1	_	\|a Talar-Wojnarowska, Renata \|b 4
700	1	_	\|a Szentesi, Andrea \|b 5
700	1	_	\|a Gazouli, Maria \|b 6
700	1	_	\|a Kreivenaite, Edita \|b 7
700	1	_	\|a Tavano, Francesca \|b 8
700	1	_	\|a Małecka-Wojciesko, Ewa \|b 9
700	1	_	\|a Erőss, Bálint \|b 10
700	1	_	\|a Oliverius, Martin \|b 11
700	1	_	\|a Bunduc, Stefania \|b 12
700	1	_	\|a Nóbrega Aoki, Mateus \|b 13
700	1	_	\|a Vodickova, Ludmila \|b 14
700	1	_	\|a Boggi, Ugo \|b 15
700	1	_	\|a Giaccherini, Matteo \|b 16
700	1	_	\|a Kondrackiene, Jurate \|b 17
700	1	_	\|a Chammas, Roger \|b 18
700	1	_	\|a Palmieri, Orazio \|b 19
700	1	_	\|a Theodoropoulos, George E \|b 20
700	1	_	\|a Bijlsma, Maarten F \|b 21
700	1	_	\|a Basso, Daniela \|b 22
700	1	_	\|a Mohelnikova-Duchonova, Beatrice \|b 23
700	1	_	\|a Soucek, Pavel \|b 24
700	1	_	\|a Izbicki, Jakob R \|b 25
700	1	_	\|a Kiudelis, Vytautas \|b 26
700	1	_	\|a Vanella, Giuseppe \|b 27
700	1	_	\|a Arcidiacono, Paolo Giorgio \|b 28
700	1	_	\|a Włodarczyk, Barbara \|b 29
700	1	_	\|a Hackert, Thilo \|b 30
700	1	_	\|a Schöttker, Ben \|0 P:(DE-He78)c67a12496b8aac150c0eef888d808d46 \|b 31 \|u dkfz
700	1	_	\|a Uzunoglu, Faik G \|b 32
700	1	_	\|a Bambi, Franco \|b 33
700	1	_	\|a Goetz, Mara \|b 34
700	1	_	\|a Hlavac, Viktor \|b 35
700	1	_	\|a Brenner, Hermann \|0 P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2 \|b 36 \|u dkfz
700	1	_	\|a Perri, Francesco \|b 37
700	1	_	\|a Carrara, Silvia \|b 38
700	1	_	\|a Landi, Stefano \|b 39
700	1	_	\|a Hegyi, Péter \|b 40
700	1	_	\|a Dijk, Frederike \|b 41
700	1	_	\|a Maiello, Evaristo \|b 42
700	1	_	\|a Capretti, Giovanni \|b 43
700	1	_	\|a Testoni, Sabrina Gloria Giulia \|b 44
700	1	_	\|a Petrone, Maria Chiara \|b 45
700	1	_	\|a Stocker, Hannah \|0 P:(DE-He78)104fae0755c89365b7ae32238b3f1f52 \|b 46 \|u dkfz
700	1	_	\|a Ermini, Stefano \|b 47
700	1	_	\|a Archibugi, Livia \|b 48
700	1	_	\|a Gentiluomo, Manuel \|b 49
700	1	_	\|a Cavestro, Giulia Martina \|b 50
700	1	_	\|a Pezzilli, Raffaele \|b 51
700	1	_	\|a Di Franco, Gregorio \|b 52
700	1	_	\|a Milanetto, Anna Caterina \|b 53
700	1	_	\|a Sperti, Cosimo \|b 54
700	1	_	\|a Neoptolemos, John P \|b 55
700	1	_	\|a Morelli, Luca \|b 56
700	1	_	\|a Vokacova, Klara \|b 57
700	1	_	\|a Pasquali, Claudio \|b 58
700	1	_	\|a Lawlor, Rita T \|b 59
700	1	_	\|a Bazzocchi, Francesca \|b 60
700	1	_	\|a Kupcinskas, Juozas \|b 61
700	1	_	\|a Capurso, Gabriele \|b 62
700	1	_	\|a Campa, Daniele \|b 63
700	1	_	\|a Canzian, Federico \|0 P:(DE-He78)5323704270b6393dcea70186ffd86bca \|b 64 \|e Last author \|u dkfz
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Marc 21

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