Identification of Recessively Inherited Genetic Variants
Potentially Linked to Pancreatic Cancer Risk

J 2021

Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk

LU, Y., M. GENTILUOMO, A. MACAUDA, D. GIOFFREDA, M. GAZOULI et. al.

Basic information

Original name

Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk

Authors

LU, Y., M. GENTILUOMO, A. MACAUDA, D. GIOFFREDA, M. GAZOULI, M. C. PETRONE, D. KELEMEN, L. GINOCCHI, L. MORELLI, K. PAPIRIS, W. GREENHALF, J. R. IZBICKI, V. KIUDELIS, Beatrice MOHELNIKOVA-DUCHONOVA (203 Czech Republic), B. BUENO-DE-MESQUITA, Pavel VODICKA (203 Czech Republic), H. BRENNER, M. K. DIENER, R. PEZZILLI, A. IVANAUSKAS, R. SALVIA, A. SZENTESI, M. N. AOKI, B. C. NEMETH, C. SPERTI, K. JAMROZIAK, R. CHAMMAS, M. OLIVERIUS, L. ARCHIBUGI, S. ERMINI, J. NOVAK, J. KUPCINSKAS, Ondrej STROUHAL (203 Czech Republic), Pavel SOUCEK (203 Czech Republic), G. M. CAVESTRO, A. C. MILANETTO, G. VANELLA, J. P. NEOPTOLEMOS, G. E. THEODOROPOULOS, H. W. M. VAN LAARHOVEN, A. MAMBRINI, S. MOZ, Zdeněk KALA (203 Czech Republic, belonging to the institution), Martin LOVECEK (203 Czech Republic), D. BASSO, F. G. UZUNOGLU, T. HACKERT, S. G. G. TESTONI, Viktor HLAVAC (203 Czech Republic), A. ANDRIULLI, M. LUCCHESI, F. TAVANO, S. CARRARA, P. HEGYI, P. G. ARCIDIACONO, O. R. BUSCH, R. T. LAWLOR, M. PUZZONO, U. BOGGI, F. GUO, E. MALECKA-PANAS, G. CAPURSO, S. LANDI, R. TALAR-WOJNAROWSKA, O. STROBEL, X. GAO, Y. VASHIST, D. CAMPA and F. CANZIAN (guarantor)

Edition

Frontiers in Oncology, Lausanne, Frontiers Media S.A. 2021, 2234-943X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.738

RIV identification code

RIV/00216224:14110/21:00124364

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3389/fonc.2021.771312

UT WoS

000761072100001

Keywords in English

pancreatic cancer; susceptibility; genome-wide association study; recessive model; genetic polymorphisms

Abstract

V originále

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p<10(-5)) compared with the additive effects (p>10(-3)), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5x10(-8)). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.

Citovat

LU, Y., M. GENTILUOMO, A. MACAUDA, D. GIOFFREDA, M. GAZOULI, M. C. PETRONE, D. KELEMEN, L. GINOCCHI, L. MORELLI, K. PAPIRIS, W. GREENHALF, J. R. IZBICKI, V. KIUDELIS, Beatrice MOHELNIKOVA-DUCHONOVA, B. BUENO-DE-MESQUITA, Pavel VODICKA, H. BRENNER, M. K. DIENER, R. PEZZILLI, A. IVANAUSKAS, R. SALVIA, A. SZENTESI, M. N. AOKI, B. C. NEMETH, C. SPERTI, K. JAMROZIAK, R. CHAMMAS, M. OLIVERIUS, L. ARCHIBUGI, S. ERMINI, J. NOVAK, J. KUPCINSKAS, Ondrej STROUHAL, Pavel SOUCEK, G. M. CAVESTRO, A. C. MILANETTO, G. VANELLA, J. P. NEOPTOLEMOS, G. E. THEODOROPOULOS, H. W. M. VAN LAARHOVEN, A. MAMBRINI, S. MOZ, Zdeněk KALA, Martin LOVECEK, D. BASSO, F. G. UZUNOGLU, T. HACKERT, S. G. G. TESTONI, Viktor HLAVAC, A. ANDRIULLI, M. LUCCHESI, F. TAVANO, S. CARRARA, P. HEGYI, P. G. ARCIDIACONO, O. R. BUSCH, R. T. LAWLOR, M. PUZZONO, U. BOGGI, F. GUO, E. MALECKA-PANAS, G. CAPURSO, S. LANDI, R. TALAR-WOJNAROWSKA, O. STROBEL, X. GAO, Y. VASHIST, D. CAMPA and F. CANZIAN. Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk. Frontiers in Oncology. Lausanne: Frontiers Media S.A., 2021, vol. 11, December 2021, p. 1-10. ISSN 2234-943X. Available from: https://dx.doi.org/10.3389/fonc.2021.771312.

@article{1839258,
   author = {Lu, Y. and Gentiluomo, M. and Macauda, A. and Gioffreda, D. and Gazouli, M. and Petrone, M. C. and Kelemen, D. and Ginocchi, L. and Morelli, L. and Papiris, K. and Greenhalf, W. and Izbicki, J. R. and Kiudelis, V. and MohelnikovaandDuchonova, Beatrice and BuenoanddeandMesquita, B. and Vodicka, Pavel and Brenner, H. and Diener, M. K. and Pezzilli, R. and Ivanauskas, A. and Salvia, R. and Szentesi, A. and Aoki, M. N. and Nemeth, B. C. and Sperti, C. and Jamroziak, K. and Chammas, R. and Oliverius, M. and Archibugi, L. and Ermini, S. and Novak, J. and Kupcinskas, J. and Strouhal, Ondrej and Soucek, Pavel and Cavestro, G. M. and Milanetto, A. C. and Vanella, G. and Neoptolemos, J. P. and Theodoropoulos, G. E. and van Laarhoven, H. W. M. and Mambrini, A. and Moz, S. and Kala, Zdeněk and Lovecek, Martin and Basso, D. and Uzunoglu, F. G. and Hackert, T. and Testoni, S. G. G. and Hlavac, Viktor and Andriulli, A. and Lucchesi, M. and Tavano, F. and Carrara, S. and Hegyi, P. and Arcidiacono, P. G. and Busch, O. R. and Lawlor, R. T. and Puzzono, M. and Boggi, U. and Guo, F. and MaleckaandPanas, E. and Capurso, G. and Landi, S. and TalarandWojnarowska, R. and Strobel, O. and Gao, X. and Vashist, Y. and Campa, D. and Canzian, F.},
   article_location = {Lausanne},
   article_number = {December 2021},
   doi = {http://dx.doi.org/10.3389/fonc.2021.771312},
   keywords = {pancreatic cancer; susceptibility; genome-wide association study; recessive model; genetic polymorphisms},
   language = {eng},
   issn = {2234-943X},
   journal = {Frontiers in Oncology},
   title = {Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk},
   url = {https://www.frontiersin.org/articles/10.3389/fonc.2021.771312/full},
   volume = {11},
   year = {2021}
}

TY  - JOUR
ID  - 1839258
AU  - Lu, Y. - Gentiluomo, M. - Macauda, A. - Gioffreda, D. - Gazouli, M. - Petrone, M. C. - Kelemen, D. - Ginocchi, L. - Morelli, L. - Papiris, K. - Greenhalf, W. - Izbicki, J. R. - Kiudelis, V. - Mohelnikova-Duchonova, Beatrice - Bueno-de-Mesquita, B. - Vodicka, Pavel - Brenner, H. - Diener, M. K. - Pezzilli, R. - Ivanauskas, A. - Salvia, R. - Szentesi, A. - Aoki, M. N. - Nemeth, B. C. - Sperti, C. - Jamroziak, K. - Chammas, R. - Oliverius, M. - Archibugi, L. - Ermini, S. - Novak, J. - Kupcinskas, J. - Strouhal, Ondrej - Soucek, Pavel - Cavestro, G. M. - Milanetto, A. C. - Vanella, G. - Neoptolemos, J. P. - Theodoropoulos, G. E. - van Laarhoven, H. W. M. - Mambrini, A. - Moz, S. - Kala, Zdeněk - Lovecek, Martin - Basso, D. - Uzunoglu, F. G. - Hackert, T. - Testoni, S. G. G. - Hlavac, Viktor - Andriulli, A. - Lucchesi, M. - Tavano, F. - Carrara, S. - Hegyi, P. - Arcidiacono, P. G. - Busch, O. R. - Lawlor, R. T. - Puzzono, M. - Boggi, U. - Guo, F. - Malecka-Panas, E. - Capurso, G. - Landi, S. - Talar-Wojnarowska, R. - Strobel, O. - Gao, X. - Vashist, Y. - Campa, D. - Canzian, F.
PY  - 2021
TI  - Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk
JF  - Frontiers in Oncology
VL  - 11
IS  - December 2021
SP  - 1-10
EP  - 1-10
PB  - Frontiers Media S.A.
SN  - 2234943X
KW  - pancreatic cancer
KW  - susceptibility
KW  - genome-wide association study
KW  - recessive model
KW  - genetic polymorphisms
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2021.771312/full
N2  - Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p<10(-5)) compared with the additive effects (p>10(-3)), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5x10(-8)). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.
ER  -

LU, Y., M. GENTILUOMO, A. MACAUDA, D. GIOFFREDA, M. GAZOULI, M. C. PETRONE, D. KELEMEN, L. GINOCCHI, L. MORELLI, K. PAPIRIS, W. GREENHALF, J. R. IZBICKI, V. KIUDELIS, Beatrice MOHELNIKOVA-DUCHONOVA, B. BUENO-DE-MESQUITA, Pavel VODICKA, H. BRENNER, M. K. DIENER, R. PEZZILLI, A. IVANAUSKAS, R. SALVIA, A. SZENTESI, M. N. AOKI, B. C. NEMETH, C. SPERTI, K. JAMROZIAK, R. CHAMMAS, M. OLIVERIUS, L. ARCHIBUGI, S. ERMINI, J. NOVAK, J. KUPCINSKAS, Ondrej STROUHAL, Pavel SOUCEK, G. M. CAVESTRO, A. C. MILANETTO, G. VANELLA, J. P. NEOPTOLEMOS, G. E. THEODOROPOULOS, H. W. M. VAN LAARHOVEN, A. MAMBRINI, S. MOZ, Zdeněk KALA, Martin LOVECEK, D. BASSO, F. G. UZUNOGLU, T. HACKERT, S. G. G. TESTONI, Viktor HLAVAC, A. ANDRIULLI, M. LUCCHESI, F. TAVANO, S. CARRARA, P. HEGYI, P. G. ARCIDIACONO, O. R. BUSCH, R. T. LAWLOR, M. PUZZONO, U. BOGGI, F. GUO, E. MALECKA-PANAS, G. CAPURSO, S. LANDI, R. TALAR-WOJNAROWSKA, O. STROBEL, X. GAO, Y. VASHIST, D. CAMPA and F. CANZIAN. Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk. \textit{Frontiers in Oncology}. Lausanne: Frontiers Media S.A., 2021, vol.~11, December 2021, p.~1-10. ISSN~2234-943X. Available from: https://dx.doi.org/10.3389/fonc.2021.771312.

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