American Association for Cancer Research (AACR)

Cancer Epidemiology Biomarkers and Prevention

, volume 28 , issue 7 , pages 1238-1245

Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study

Fei Chen ¹

Erica J. Childs ²

Evelina Mocci ²

Paige Bracci ³

Steven Gallinger ⁴

Donghui Li ⁵

Rachel E. Neale ⁶

Sara H. Olson ⁷

Ghislaine Scelo ⁸

William R. Bamlet ⁹

Amanda L Blackford ²

Michael Borges ¹⁰

Paul Brennan ⁸

Kari G. Rabe ⁹

Priya Duggal ¹

Manal J Hassan ⁵

Elizabeth A. Holly ³

Rayjean J. Hung ¹¹

Michael G. Goggins ¹⁰

Robert C Kurtz ¹²

Ann L Oberg ⁹

I Orlow ⁷

Herbert Yu ¹³

Gloria M. Petersen ⁹

Harvey A. Risch ¹⁴

Alison Klein ^{1, 2, 10}

Hide authors affiliations Show authors affiliations: 14 affiliations

1Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland. |

2Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. |

3Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California. |

⁴

4Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. |

⁵

5Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. |

⁶

6Department of Population Health, QIMR Berghofer Medical Research Institute, Queensland, Australia. |

⁷

7Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. |

⁸

8International Agency for Research on Cancer (IARC), Lyon, France. |

⁹

9Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota. |

¹⁰

10Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. |

¹¹

11Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada. |

¹²

12Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. |

¹³

13Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii. |

¹⁴

14Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. |

Publication type: Journal Article

Publication date: 2019-07-01

American Association for Cancer Research (AACR)

Cancer Epidemiology Biomarkers and Prevention

scimago Q1

wos Q1

SJR: 1.939

CiteScore: 6.4

Impact factor: 3.4

ISSN: 10559965, 15387755

DOI: 10.1158/1055-9965.epi-18-1235

Copy DOI

PubMed ID: 31015203

Oncology

Epidemiology

Abstract

Background:

Pancreatic cancer is the fourth-leading cause of cancer death in both men and women in the United States. The currently identified common susceptibility loci account for a small fraction of estimated heritability. We sought to estimate overall heritability of pancreatic cancer and partition the heritability by variant frequencies and functional annotations.

Methods:

Analysis using the genome-based restricted maximum likelihood method (GREML) was conducted on Pancreatic Cancer Case-Control Consortium (PanC4) genome-wide association study (GWAS) data from 3,568 pancreatic cancer cases and 3,363 controls of European Ancestry.

Results:

Applying linkage disequilibrium- and minor allele frequency-stratified GREML (GREML-LDMS) method to imputed GWAS data, we estimated the overall heritability of pancreatic cancer to be 21.2% (SE = 4.8%). Across the functional groups (intronic, intergenic, coding, and regulatory variants), intronic variants account for most of the estimated heritability (12.4%). Previously identified GWAS loci explained 4.1% of the total phenotypic variation of pancreatic cancer. Mutations in hereditary pancreatic cancer susceptibility genes are present in 4% to 10% of patients with pancreatic cancer, yet our GREML-LDMS results suggested these regions explain only 0.4% of total phenotypic variance for pancreatic cancer.

Conclusions:

Although higher than previous studies, our estimated 21.2% overall heritability may still be downwardly biased due to the inherent limitation that the contribution of rare variants in genes with a substantive overall impact on disease are not captured when applying these commonly used methods to imputed GWAS data.

Impact:

Our work demonstrated the importance of rare and common variants in pancreatic cancer risk.

Found

Top-30

Journals

	1 2 3
Cancers	Cancers, 3, 5.17% Cancers 3 publications, 5.17%
Cancer Epidemiology Biomarkers and Prevention	Cancer Epidemiology Biomarkers and Prevention, 3, 5.17% Cancer Epidemiology Biomarkers and Prevention 3 publications, 5.17%
Metabolites	Metabolites, 2, 3.45% Metabolites 2 publications, 3.45%
Frontiers in Oncology	Frontiers in Oncology, 2, 3.45% Frontiers in Oncology 2 publications, 3.45%
Cancer Research	Cancer Research, 2, 3.45% Cancer Research 2 publications, 3.45%
Hepatology	Hepatology, 2, 3.45% Hepatology 2 publications, 3.45%
Current Opinion in Gastroenterology	Current Opinion in Gastroenterology, 1, 1.72% Current Opinion in Gastroenterology 1 publication, 1.72%
American Journal of Gastroenterology	American Journal of Gastroenterology, 1, 1.72% American Journal of Gastroenterology 1 publication, 1.72%
International Journal of Environmental Research and Public Health	International Journal of Environmental Research and Public Health, 1, 1.72% International Journal of Environmental Research and Public Health 1 publication, 1.72%
Cancer and Metastasis Reviews	Cancer and Metastasis Reviews, 1, 1.72% Cancer and Metastasis Reviews 1 publication, 1.72%
Genome Medicine	Genome Medicine, 1, 1.72% Genome Medicine 1 publication, 1.72%
Nature Reviews Gastroenterology and Hepatology	Nature Reviews Gastroenterology and Hepatology, 1, 1.72% Nature Reviews Gastroenterology and Hepatology 1 publication, 1.72%
InFo Hämatologie + Onkologie	InFo Hämatologie + Onkologie, 1, 1.72% InFo Hämatologie + Onkologie 1 publication, 1.72%
Hereditary Cancer in Clinical Practice	Hereditary Cancer in Clinical Practice, 1, 1.72% Hereditary Cancer in Clinical Practice 1 publication, 1.72%
Onkologe	Onkologe, 1, 1.72% Onkologe 1 publication, 1.72%
Modern Pathology	Modern Pathology, 1, 1.72% Modern Pathology 1 publication, 1.72%
Journal of Gastroenterology	Journal of Gastroenterology, 1, 1.72% Journal of Gastroenterology 1 publication, 1.72%
Gastrointestinal Endoscopy Clinics of North America	Gastrointestinal Endoscopy Clinics of North America, 1, 1.72% Gastrointestinal Endoscopy Clinics of North America 1 publication, 1.72%
Seminars in Cancer Biology	Seminars in Cancer Biology, 1, 1.72% Seminars in Cancer Biology 1 publication, 1.72%
Cancer Treatment Reviews	Cancer Treatment Reviews, 1, 1.72% Cancer Treatment Reviews 1 publication, 1.72%
Hematology/Oncology Clinics of North America	Hematology/Oncology Clinics of North America, 1, 1.72% Hematology/Oncology Clinics of North America 1 publication, 1.72%
Biochimica et Biophysica Acta - Reviews on Cancer	Biochimica et Biophysica Acta - Reviews on Cancer, 1, 1.72% Biochimica et Biophysica Acta - Reviews on Cancer 1 publication, 1.72%
The Lancet Gastroenterology and Hepatology	The Lancet Gastroenterology and Hepatology, 1, 1.72% The Lancet Gastroenterology and Hepatology 1 publication, 1.72%
EBioMedicine	EBioMedicine, 1, 1.72% EBioMedicine 1 publication, 1.72%
Journal of Biomedical Informatics	Journal of Biomedical Informatics, 1, 1.72% Journal of Biomedical Informatics 1 publication, 1.72%
Seminars in Oncology	Seminars in Oncology, 1, 1.72% Seminars in Oncology 1 publication, 1.72%
Pancreatology	Pancreatology, 1, 1.72% Pancreatology 1 publication, 1.72%
American Journal of Clinical Nutrition	American Journal of Clinical Nutrition, 1, 1.72% American Journal of Clinical Nutrition 1 publication, 1.72%
Journal of Medical Genetics	Journal of Medical Genetics, 1, 1.72% Journal of Medical Genetics 1 publication, 1.72%
	1 2 3

Publishers

	2 4 6 8 10 12 14 16
Elsevier	Elsevier, 15, 25.86% Elsevier 15 publications, 25.86%
Springer Nature	Springer Nature, 11, 18.97% Springer Nature 11 publications, 18.97%
MDPI	MDPI, 7, 12.07% MDPI 7 publications, 12.07%
American Association for Cancer Research (AACR)	American Association for Cancer Research (AACR), 5, 8.62% American Association for Cancer Research (AACR) 5 publications, 8.62%
Ovid Technologies (Wolters Kluwer Health)	Ovid Technologies (Wolters Kluwer Health), 4, 6.9% Ovid Technologies (Wolters Kluwer Health) 4 publications, 6.9%
Wiley	Wiley, 4, 6.9% Wiley 4 publications, 6.9%
Frontiers Media S.A.	Frontiers Media S.A., 2, 3.45% Frontiers Media S.A. 2 publications, 3.45%
Oxford University Press	Oxford University Press, 2, 3.45% Oxford University Press 2 publications, 3.45%
American Society for Nutrition	American Society for Nutrition, 1, 1.72% American Society for Nutrition 1 publication, 1.72%
BMJ	BMJ, 1, 1.72% BMJ 1 publication, 1.72%
American Diabetes Association	American Diabetes Association, 1, 1.72% American Diabetes Association 1 publication, 1.72%
Taylor & Francis	Taylor & Francis, 1, 1.72% Taylor & Francis 1 publication, 1.72%
Tomsk Cancer Research Institute	Tomsk Cancer Research Institute, 1, 1.72% Tomsk Cancer Research Institute 1 publication, 1.72%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 1, 1.72% Cold Spring Harbor Laboratory 1 publication, 1.72%
Moffitt Cancer Center	Moffitt Cancer Center, 1, 1.72% Moffitt Cancer Center 1 publication, 1.72%
	2 4 6 8 10 12 14 16

We do not take into account publications without a DOI.
Statistics recalculated weekly.

Are you a researcher?

Create a profile to get free access to personal recommendations for colleagues and new articles.

Metrics

Cite this

GOST |

Cite this

GOST Copy

Chen F. et al. Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study // Cancer Epidemiology Biomarkers and Prevention. 2019. Vol. 28. No. 7. pp. 1238-1245.

GOST all authors (up to 50) Copy

Chen F., Childs E. J., Mocci E., Bracci P., Gallinger S., Li D., Neale R. E., Olson S. H., Scelo G., Bamlet W. R., Blackford A. L., Borges M., Brennan P., Rabe K. G., Duggal P., Hassan M. J., Holly E. A., Hung R. J., Goggins M. G., Kurtz R. C., Oberg A. L., Orlow I., Yu H., Petersen G. M., Risch H. A., Klein A. Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study // Cancer Epidemiology Biomarkers and Prevention. 2019. Vol. 28. No. 7. pp. 1238-1245.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1158/1055-9965.epi-18-1235

UR - https://doi.org/10.1158/1055-9965.epi-18-1235

TI - Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study

T2 - Cancer Epidemiology Biomarkers and Prevention

AU - Chen, Fei

AU - Childs, Erica J.

AU - Mocci, Evelina

AU - Bracci, Paige

AU - Gallinger, Steven

AU - Li, Donghui

AU - Neale, Rachel E.

AU - Olson, Sara H.

AU - Scelo, Ghislaine

AU - Bamlet, William R.

AU - Blackford, Amanda L

AU - Borges, Michael

AU - Brennan, Paul

AU - Rabe, Kari G.

AU - Duggal, Priya

AU - Hassan, Manal J

AU - Holly, Elizabeth A.

AU - Hung, Rayjean J.

AU - Goggins, Michael G.

AU - Kurtz, Robert C

AU - Oberg, Ann L

AU - Orlow, I

AU - Yu, Herbert

AU - Petersen, Gloria M.

AU - Risch, Harvey A.

AU - Klein, Alison

PY - 2019

DA - 2019/07/01

PB - American Association for Cancer Research (AACR)

SP - 1238-1245

IS - 7

VL - 28

PMID - 31015203

SN - 1055-9965

SN - 1538-7755

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2019_Chen,

author = {Fei Chen and Erica J. Childs and Evelina Mocci and Paige Bracci and Steven Gallinger and Donghui Li and Rachel E. Neale and Sara H. Olson and Ghislaine Scelo and William R. Bamlet and Amanda L Blackford and Michael Borges and Paul Brennan and Kari G. Rabe and Priya Duggal and Manal J Hassan and Elizabeth A. Holly and Rayjean J. Hung and Michael G. Goggins and Robert C Kurtz and Ann L Oberg and I Orlow and Herbert Yu and Gloria M. Petersen and Harvey A. Risch and Alison Klein},

title = {Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study},

journal = {Cancer Epidemiology Biomarkers and Prevention},

year = {2019},

volume = {28},

publisher = {American Association for Cancer Research (AACR)},

month = {jul},

url = {https://doi.org/10.1158/1055-9965.epi-18-1235},

number = {7},

pages = {1238--1245},

doi = {10.1158/1055-9965.epi-18-1235}

}

MLA

Cite this

MLA Copy

Chen, Fei, et al. “Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study.” Cancer Epidemiology Biomarkers and Prevention, vol. 28, no. 7, Jul. 2019, pp. 1238-1245. https://doi.org/10.1158/1055-9965.epi-18-1235.

Publisher

American Association for Cancer Research (AACR)

Journal

Cancer Epidemiology Biomarkers and Prevention

scimago Q1

wos Q1

SJR

1.939

CiteScore

6.4

Impact factor

3.4

ISSN

10559965 (Print)

15387755 (Electronic)