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.

Základní údaje

Originální název

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

Autoři

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 Česká republika), B. BUENO-DE-MESQUITA, Pavel VODICKA (203 Česká republika), 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 Česká republika), Pavel SOUCEK (203 Česká republika), 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 Česká republika, domácí), Martin LOVECEK (203 Česká republika), D. BASSO, F. G. UZUNOGLU, T. HACKERT, S. G. G. TESTONI, Viktor HLAVAC (203 Česká republika), 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 a F. CANZIAN (garant)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.738

Kód RIV

RIV/00216224:14110/21:00124364

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000761072100001

Klíčová slova anglicky

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

Štítky

14110223, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 3. 2022 14:24, Mgr. Tereza Miškechová

Anotace

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 a F. CANZIAN. Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk. Frontiers in Oncology. Lausanne: Frontiers Media S.A., 2021, roč. 11, December 2021, s. 1-10. ISSN 2234-943X. Dostupné z: 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 a F. CANZIAN. Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk. \textit{Frontiers in Oncology}. Lausanne: Frontiers Media S.A., 2021, roč.~11, December 2021, s.~1-10. ISSN~2234-943X. Dostupné z: https://dx.doi.org/10.3389/fonc.2021.771312.

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