Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

Margherita Piccardi; Manuel Gentiluomo; Stefania Bertoncini; Raffaele Pezzilli; B. lint Erőss; Stefania Bunduc; Faik G. Uzunoglu; Renata Talar-Wojnarowska; Tomas Vanagas; Cosimo Sperti; Martin Oliverius; Mateus N. brega Aoki; Stefano Ermini; Tamás Hussein; Ugo Boggi; Krzysztof Jamroziak; Evaristo Maiello; Luca Morelli; Ludmila Vodickova; Gregorio di Franco; Stefano Landi; Andrea Szentesi; Martin Lovecek; Marta Puzzono; Francesca Tavano; Hanneke W. M. van Laarhoven; Alessandro Zerbi; Beatrice Mohelnikova-Duchonova; Hannah Stocker; Eithne Costello; Gabriele Capurso; Laura Ginocchi; Rita T. Lawlor; Giuseppe Vanella; Francesca Bazzocchi; Jakob R. Izbicki; Anna Latiano; Bas Bueno-de-Mesquita; Ruggero Ponz de Leon Pisani; Ben Schöttker; Pavel Soucek; P. ter Hegyi; Maria Gazouli; Thilo Hackert; Juozas Kupcinskas; Lina Poskiene; Matteo Tacelli; Susanne Roth; Silvia Carrara; Francesco Perri; Viktor Hlavac; George E. Theodoropoulos; Olivier R. Busch; Andrea Mambrini; Casper H. J. van Eijck; Paolo Arcidiacono; Aldo Scarpa; Claudio Pasquali; Daniela Basso; Maurizio Lucchesi; Anna Caterina Milanetto; John P. Neoptolemos; Giulia Martina Cavestro; Dainius Janciauskas; Xuechen Chen; Roger Chammas; Mara Goetz; Hermann Brenner; Livia Archibugi; Michael Dannemann; Federico Canzian; Sergio Tofanelli; Daniele Campa

doi:https://doi.org/10.1186/s40659-023-00457-y

Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

Margherita Piccardi, Manuel Gentiluomo, Stefania Bertoncini, Raffaele Pezzilli, B. lint Erőss, Stefania Bunduc, Faik G. Uzunoglu, Renata Talar-Wojnarowska, Tomas Vanagas, Cosimo Sperti, Martin Oliverius, Mateus N. brega Aoki, Stefano Ermini, Tamás Hussein, Ugo Boggi, Krzysztof Jamroziak, Evaristo Maiello, Luca Morelli, Ludmila Vodickova, Gregorio di FrancoStefano Landi, Andrea Szentesi, Martin Lovecek, Marta Puzzono, Francesca Tavano, Hanneke W. M. van Laarhoven, Alessandro Zerbi, Beatrice Mohelnikova-Duchonova, Hannah Stocker, Eithne Costello, Gabriele Capurso, Laura Ginocchi, Rita T. Lawlor, Giuseppe Vanella, Francesca Bazzocchi, Jakob R. Izbicki, Anna Latiano, Bas Bueno-de-Mesquita, Ruggero Ponz de Leon Pisani, Ben Schöttker, Pavel Soucek, P. ter Hegyi, Maria Gazouli, Thilo Hackert, Juozas Kupcinskas, Lina Poskiene, Matteo Tacelli, Susanne Roth, Silvia Carrara, Francesco Perri, Viktor Hlavac, George E. Theodoropoulos, Olivier R. Busch, Andrea Mambrini, Casper H. J. van Eijck, Paolo Arcidiacono, Aldo Scarpa, Claudio Pasquali, Daniela Basso, Maurizio Lucchesi, Anna Caterina Milanetto, John P. Neoptolemos, Giulia Martina Cavestro, Dainius Janciauskas, Xuechen Chen, Roger Chammas, Mara Goetz, Hermann Brenner, Livia Archibugi, Michael Dannemann, Federico Canzian, Sergio Tofanelli, Daniele Campa

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Original language	English
Article number	46
Journal	Biological Research
Volume	56
Issue number	1
DOIs	https://doi.org/10.1186/s40659-023-00457-y
Publication status	Published - 1 Dec 2023

Keywords

Admixture
Association study
Eurasians
Introgression
Neandertal
Pancreatic cancer

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https://doi.org/10.1186/s40659-023-00457-y

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Piccardi, M., Gentiluomo, M., Bertoncini, S., Pezzilli, R., Erőss, B. L., Bunduc, S., Uzunoglu, F. G., Talar-Wojnarowska, R., Vanagas, T., Sperti, C., Oliverius, M., Aoki, M. N. B., Ermini, S., Hussein, T., Boggi, U., Jamroziak, K., Maiello, E., Morelli, L., Vodickova, L., ... Campa, D. (2023). Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians. Biological Research, 56(1), Article 46. https://doi.org/10.1186/s40659-023-00457-y

@article{4bb356d3447a45feaf4013bbc8435254,

title = "Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians",

abstract = "Background: The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.",

keywords = "Admixture, Association study, Eurasians, Introgression, Neandertal, Pancreatic cancer",

author = "Margherita Piccardi and Manuel Gentiluomo and Stefania Bertoncini and Raffaele Pezzilli and Er{\H o}ss, {B. lint} and Stefania Bunduc and Uzunoglu, {Faik G.} and Renata Talar-Wojnarowska and Tomas Vanagas and Cosimo Sperti and Martin Oliverius and Aoki, {Mateus N. brega} and Stefano Ermini and Tam{\'a}s Hussein and Ugo Boggi and Krzysztof Jamroziak and Evaristo Maiello and Luca Morelli and Ludmila Vodickova and {di Franco}, Gregorio and Stefano Landi and Andrea Szentesi and Martin Lovecek and Marta Puzzono and Francesca Tavano and {van Laarhoven}, {Hanneke W. M.} and Alessandro Zerbi and Beatrice Mohelnikova-Duchonova and Hannah Stocker and Eithne Costello and Gabriele Capurso and Laura Ginocchi and Lawlor, {Rita T.} and Giuseppe Vanella and Francesca Bazzocchi and Izbicki, {Jakob R.} and Anna Latiano and Bas Bueno-de-Mesquita and {Ponz de Leon Pisani}, Ruggero and Ben Sch{\"o}ttker and Pavel Soucek and Hegyi, {P. ter} and Maria Gazouli and Thilo Hackert and Juozas Kupcinskas and Lina Poskiene and Matteo Tacelli and Susanne Roth and Silvia Carrara and Francesco Perri and Viktor Hlavac and Theodoropoulos, {George E.} and Busch, {Olivier R.} and Andrea Mambrini and {van Eijck}, {Casper H. J.} and Paolo Arcidiacono and Aldo Scarpa and Claudio Pasquali and Daniela Basso and Maurizio Lucchesi and Milanetto, {Anna Caterina} and Neoptolemos, {John P.} and Cavestro, {Giulia Martina} and Dainius Janciauskas and Xuechen Chen and Roger Chammas and Mara Goetz and Hermann Brenner and Livia Archibugi and Michael Dannemann and Federico Canzian and Sergio Tofanelli and Daniele Campa",

note = "Funding Information: This article is based upon work from COST Action “Identification of biological markers for prevention and translational medicine in pancreatic cancer (TRANSPAN)”, CA21116, supported by COST (European Cooperation in Science and Technology). This research used genotyping data provided to the PANDoRA consortium by the EPIC cohort, for which we would like to thank the contributors from EPIC UK. We want to acknowledge the participants and investigators of the FinnGen study. Funding Information: This study was supported by Associazione Italiana Ricerca Cancro (AIRC IG n. 26343) [Aldo Scarpa], Italian Ministry of Health (FIMPCUP_J38D19000690001) [Aldo Scarpa], the Ministry of Health of the Czech Republic (Grant number NV19-08–00113) [Pavel Soucek], Cancer Research UK (C7690/A26881) [Eithne Costello], Pancreatic Cancer UK Research Innovation Fund [Eithne Costello], Charles University Research Fund (Cooperatio No. 43 -Surgical Disciplines) [Ludmila Vodickova], Ministry of Health of the Czech Republic (AZV NU21-07–00247) [Ludmila Vodickova], Ministry of Health of the Czech Republic (grant no. NV19-03–00097 to B.M-D.) [Beatrice Moheln{\'i}kov{\'a} Ducho{\v n}ov{\'a}], Italian Ministry of Health grants to Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, San Giovanni Rotondo (FG), Italy [Francesco Perri], and by the “5 × 1000” voluntary contribution [Francesco Perri]. Funding Information: This article is based upon work from COST Action “Identification of biological markers for prevention and translational medicine in pancreatic cancer (TRANSPAN) ”, CA21116, supported by COST (European Cooperation in Science and Technology). This research used genotyping data provided to the PANDoRA consortium by the EPIC cohort, for which we would like to thank the contributors from EPIC UK. We want to acknowledge the participants and investigators of the FinnGen study. Publisher Copyright: {\textcopyright} 2023, Sociedad de Biologia de Chile.",

year = "2023",

month = dec,

day = "1",

doi = "https://doi.org/10.1186/s40659-023-00457-y",

language = "English",

volume = "56",

journal = "Biological Research",

issn = "0716-9760",

publisher = "BioMed Central Ltd.",

number = "1",

}

Piccardi, M, Gentiluomo, M, Bertoncini, S, Pezzilli, R, Erőss, BL, Bunduc, S, Uzunoglu, FG, Talar-Wojnarowska, R, Vanagas, T, Sperti, C, Oliverius, M, Aoki, MNB, Ermini, S, Hussein, T, Boggi, U, Jamroziak, K, Maiello, E, Morelli, L, Vodickova, L, di Franco, G, Landi, S, Szentesi, A, Lovecek, M, Puzzono, M, Tavano, F, van Laarhoven, HWM, Zerbi, A, Mohelnikova-Duchonova, B, Stocker, H, Costello, E, Capurso, G, Ginocchi, L, Lawlor, RT, Vanella, G, Bazzocchi, F, Izbicki, JR, Latiano, A, Bueno-de-Mesquita, B, Ponz de Leon Pisani, R, Schöttker, B, Soucek, P, Hegyi, PT, Gazouli, M, Hackert, T, Kupcinskas, J, Poskiene, L, Tacelli, M, Roth, S, Carrara, S, Perri, F, Hlavac, V, Theodoropoulos, GE, Busch, OR, Mambrini, A, van Eijck, CHJ, Arcidiacono, P, Scarpa, A, Pasquali, C, Basso, D, Lucchesi, M, Milanetto, AC, Neoptolemos, JP, Cavestro, GM, Janciauskas, D, Chen, X, Chammas, R, Goetz, M, Brenner, H, Archibugi, L, Dannemann, M, Canzian, F, Tofanelli, S & Campa, D 2023, 'Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians', Biological Research, vol. 56, no. 1, 46. https://doi.org/10.1186/s40659-023-00457-y

TY - JOUR

T1 - Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

AU - Piccardi, Margherita

AU - Gentiluomo, Manuel

AU - Bertoncini, Stefania

AU - Pezzilli, Raffaele

AU - Erőss, B. lint

AU - Bunduc, Stefania

AU - Uzunoglu, Faik G.

AU - Talar-Wojnarowska, Renata

AU - Vanagas, Tomas

AU - Sperti, Cosimo

AU - Oliverius, Martin

AU - Aoki, Mateus N. brega

AU - Ermini, Stefano

AU - Hussein, Tamás

AU - Boggi, Ugo

AU - Jamroziak, Krzysztof

AU - Maiello, Evaristo

AU - Morelli, Luca

AU - Vodickova, Ludmila

AU - di Franco, Gregorio

AU - Landi, Stefano

AU - Szentesi, Andrea

AU - Lovecek, Martin

AU - Puzzono, Marta

AU - Tavano, Francesca

AU - van Laarhoven, Hanneke W. M.

AU - Zerbi, Alessandro

AU - Mohelnikova-Duchonova, Beatrice

AU - Stocker, Hannah

AU - Costello, Eithne

AU - Capurso, Gabriele

AU - Ginocchi, Laura

AU - Lawlor, Rita T.

AU - Vanella, Giuseppe

AU - Bazzocchi, Francesca

AU - Izbicki, Jakob R.

AU - Latiano, Anna

AU - Bueno-de-Mesquita, Bas

AU - Ponz de Leon Pisani, Ruggero

AU - Schöttker, Ben

AU - Soucek, Pavel

AU - Hegyi, P. ter

AU - Gazouli, Maria

AU - Hackert, Thilo

AU - Kupcinskas, Juozas

AU - Poskiene, Lina

AU - Tacelli, Matteo

AU - Roth, Susanne

AU - Carrara, Silvia

AU - Perri, Francesco

AU - Hlavac, Viktor

AU - Theodoropoulos, George E.

AU - Busch, Olivier R.

AU - Mambrini, Andrea

AU - van Eijck, Casper H. J.

AU - Arcidiacono, Paolo

AU - Scarpa, Aldo

AU - Pasquali, Claudio

AU - Basso, Daniela

AU - Lucchesi, Maurizio

AU - Milanetto, Anna Caterina

AU - Neoptolemos, John P.

AU - Cavestro, Giulia Martina

AU - Janciauskas, Dainius

AU - Chen, Xuechen

AU - Chammas, Roger

AU - Goetz, Mara

AU - Brenner, Hermann

AU - Archibugi, Livia

AU - Dannemann, Michael

AU - Canzian, Federico

AU - Tofanelli, Sergio

AU - Campa, Daniele

N1 - Funding Information: This article is based upon work from COST Action “Identification of biological markers for prevention and translational medicine in pancreatic cancer (TRANSPAN)”, CA21116, supported by COST (European Cooperation in Science and Technology). This research used genotyping data provided to the PANDoRA consortium by the EPIC cohort, for which we would like to thank the contributors from EPIC UK. We want to acknowledge the participants and investigators of the FinnGen study. Funding Information: This study was supported by Associazione Italiana Ricerca Cancro (AIRC IG n. 26343) [Aldo Scarpa], Italian Ministry of Health (FIMPCUP_J38D19000690001) [Aldo Scarpa], the Ministry of Health of the Czech Republic (Grant number NV19-08–00113) [Pavel Soucek], Cancer Research UK (C7690/A26881) [Eithne Costello], Pancreatic Cancer UK Research Innovation Fund [Eithne Costello], Charles University Research Fund (Cooperatio No. 43 -Surgical Disciplines) [Ludmila Vodickova], Ministry of Health of the Czech Republic (AZV NU21-07–00247) [Ludmila Vodickova], Ministry of Health of the Czech Republic (grant no. NV19-03–00097 to B.M-D.) [Beatrice Mohelníková Duchoňová], Italian Ministry of Health grants to Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, San Giovanni Rotondo (FG), Italy [Francesco Perri], and by the “5 × 1000” voluntary contribution [Francesco Perri]. Funding Information: This article is based upon work from COST Action “Identification of biological markers for prevention and translational medicine in pancreatic cancer (TRANSPAN) ”, CA21116, supported by COST (European Cooperation in Science and Technology). This research used genotyping data provided to the PANDoRA consortium by the EPIC cohort, for which we would like to thank the contributors from EPIC UK. We want to acknowledge the participants and investigators of the FinnGen study. Publisher Copyright: © 2023, Sociedad de Biologia de Chile.

PY - 2023/12/1

Y1 - 2023/12/1

N2 - Background: The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

AB - Background: The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

KW - Admixture

KW - Association study

KW - Eurasians

KW - Introgression

KW - Neandertal

KW - Pancreatic cancer

UR - http://www.scopus.com/inward/record.url?scp=85168222326&partnerID=8YFLogxK

U2 - https://doi.org/10.1186/s40659-023-00457-y

DO - https://doi.org/10.1186/s40659-023-00457-y

M3 - Article

C2 - 37574541

SN - 0716-9760

VL - 56

JO - Biological Research

JF - Biological Research

IS - 1

M1 - 46

ER -

Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

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Keywords

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