Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: A pathway analysis of genome-wide association studies Journal Article
| Authors: | Julián-Serrano, S.; Yuan, F.; Wheeler, W.; Benyamin, B.; Machiela, M. J.; Arslan, A. A.; Beane-Freeman, L. E.; Bracci, P. M.; Duell, E. J.; Du, M.; Gallinger, S.; Giles, G. G.; Goodman, P. J.; Kooperberg, C.; Le Marchand, L.; Neale, R. E.; Shu, X. O.; Van Den Eeden, S. K.; Visvanathan, K.; Zheng, W.; Albanes, D.; Andreotti, G.; Ardanaz, E.; Babic, A.; Berndt, S. I.; Brais, L. K.; Brennan, P.; Bueno-De-Mesquita, B.; Buring, J. E.; Chanock, S. J.; Childs, E. J.; Chung, C. C.; Fabiánová, E.; Foretová, L.; Fuchs, C. S.; Gaziano, J. M.; Gentiluomo, M.; Giovannucci, E. L.; Goggins, M. G.; Hackert, T.; Hartge, P.; Hassan, M. M.; Holcátová, I.; Holly, E. A.; Hung, R. I.; Janout, V.; Kurtz, R. C.; Lee, I. M.; Malats, N.; McKean, D.; Milne, R. L.; Newton, C. C.; Oberg, A. L.; Perdomo, S.; Peters, U.; Porta, M.; Rothman, N.; Schulze, M. B.; Sesso, H. D.; Silverman, D. T.; Thompson, I. M.; Wactawski-Wende, J.; Weiderpass, E.; Wenstzensen, N.; White, E.; Wilkens, L. R.; Yu, H.; Zeleniuch-Jacquotte, A.; Zhong, J.; Kraft, P.; Li, D.; Campbell, P. T.; Petersen, G. M.; Wolpin, B. M.; Risch, H. A.; Amundadottir, L. T.; Klein, A. P.; Yu, K.; Stolzenberg-Solomon, R. Z. |
| Article Title: | Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: A pathway analysis of genome-wide association studies |
| Abstract: | Background: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. Objectives: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. Methods: We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs. Results: The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. Conclusions: Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association. © 2021 Published by Oxford University Press on behalf of the American Society for Nutrition 2021. |
| Keywords: | genetic susceptibility; pancreatic cancer; epidemiology; hepcidin; iron metabolism pathway |
| Journal Title: | American Journal of Clinical Nutrition |
| Volume: | 114 |
| Issue: | 4 |
| ISSN: | 0002-9165 |
| Publisher: | American Society for Nutrition |
| Date Published: | 2021-10-01 |
| Start Page: | 1408 |
| End Page: | 1417 |
| Language: | English |
| DOI: | 10.1093/ajcn/nqab217 |
| PUBMED: | 34258619 |
| PROVIDER: | scopus |
| PMCID: | PMC8488877 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2021 -- Source: Scopus |
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