Genome-wide association study data reveal genetic susceptibility to chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma risk

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• Alternative Title:
  Cancer Res
• Personal Author:
  Yuan, Fangcheng ; Hung, Rayjean J. ; Walsh, Naomi ; Zhang, Han ; Platz, Elizabeth A. ; Wheeler, William ; Song, Lei ; Arslan, Alan A. ; Freeman, Laura E. Beane ; Bracci, Paige ; Canzian, Federico ; Du, Mengmeng ; Gallinger, Steven ; Giles, Graham G. ; Goodman, Phyllis J. ; Kooperberg, Charles ; Le Marchand, Loic ; Neale, Rachel E. ; Rosendahl, Jonas ; Scelo, Ghislaine ; Shu, Xiao-Ou ; Visvanathan, Kala ; White, Emily ; Zheng, Wei ; Albanes, Demetrius ; Amiano, Pilar ; Andreotti, Gabriella ; Babic, Ana ; Bamlet, William R. ; Berndt, Sonja I. ; Brennan, Paul ; Bueno-de-Mesquita, Bas ; Buring, Julie E. ; Campbell, Peter T. ; Chanock, Stephen J. ; Fuchs, Charles S. ; Gaziano, J. Michael ; Goggins, Michael G. ; Hackert, Thilo ; Hartge, Patricia ; Hassan, Manal M. ; Holly, Elizabeth A. ; Hoover, Robert N. ; Katzke, Verena ; Kirsten, Holger ; Kurtz, Robert C. ; Lee, I-Min ; Malats, Nuria ; Milne, Roger L. ; Murphy, Neil ; Ng, Kimmie ; Oberg, Ann L. ; Porta, Miquel ; Rabe, Kari G. ; Real, Francisco X. ; Rothman, Nathaniel ; Sesso, Howard D. ; Silverman, Debra T. ; Thompson, Ian M. ; Wactawski-Wende, Jean ; Wang, Xiaoliang ; Wentzensen, Nicolas ; Wilkens, Lynne R. ; Yu, Herbert ; Zeleniuch-Jacquotte, Anne ; Shi, Jianxin ; Duell, Eric J. ; Amundadottir, Laufey T. ; Li, Donghui ; Petersen, Gloria M. ; Wolpin, Brian M. ; Risch, Harvey A. ; Yu, Kai ; Klein, Alison P. ; Stolzenberg-Solomon, Rachael
• Description:
  Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at | values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10|, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (| = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (| = 0.22) and primary sclerosing cholangitis (| = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.
• Subjects:
  Carcinoma, Pancreatic Ductal Case-Control Studies Celiac Disease Cholangitis, Sclerosing Chronic Disease Colitis, Ulcerative Crohn Disease Genetic Predisposition To Disease Genome-Wide Association Study Humans Inflammatory Bowel Diseases Pancreatic Neoplasms Pancreatitis, Chronic

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• Keywords:
  Buprenorphine Methadone Mortality Naltrexone Treatment
• Source:
  Cancer Res. 80(18):4004-4013
• Pubmed ID:
  32641412
• Pubmed Central ID:
  PMC7861352
• Document Type:
  Journal Article
• Funding:
  UM1 CA164973/CA/NCI NIH HHSUnited States/ ; P30 CA016087/CA/NCI NIH HHSUnited States/ ; P01 CA087969/CA/NCI NIH HHSUnited States/ ; UG1 CA189974/CA/NCI NIH HHSUnited States/ ; R01 HL034595/HL/NHLBI NIH HHSUnited States/ ; P30 ES000260/ES/NIEHS NIH HHSUnited States/ ; HHSN261200800001C/CA/NCI NIH HHSUnited States/ ; P50 CA102701/CA/NCI NIH HHSUnited States/ ; HHSN268201600003C/HL/NHLBI NIH HHSUnited States/ ; U58 DP003862/DP/NCCDPHP CDC HHSUnited States/ ; R01 CA050706/CA/NCI NIH HHSUnited States/ ; U01 CA247283/CA/NCI NIH HHSUnited States/ ; U10 CA037429/CA/NCI NIH HHSUnited States/ ; HHSN268201600002C/HL/NHLBI NIH HHSUnited States/ ; P50 CA062924/CA/NCI NIH HHSUnited States/ ; HHSN268201600018C/HL/NHLBI NIH HHSUnited States/ ; P30 CA006973/CA/NCI NIH HHSUnited States/ ; K07 CA222159/CA/NCI NIH HHSUnited States/ ; R01 HL043851/HL/NHLBI NIH HHSUnited States/ ; R01 CA100967/CA/NCI NIH HHSUnited States/ ; UM1 CA182934/CA/NCI NIH HHSUnited States/ ; R01 CA098870/CA/NCI NIH HHSUnited States/ ; P30 CA008748/CA/NCI NIH HHSUnited States/ ; R01 CA063464/CA/NCI NIH HHSUnited States/ ; UM1 CA186107/CA/NCI NIH HHSUnited States/ ; HHSN268201600004C/HL/NHLBI NIH HHSUnited States/ ; UM1 CA182913/CA/NCI NIH HHSUnited States/ ; R01 CA054281/CA/NCI NIH HHSUnited States/ ; R01 HL026490/HL/NHLBI NIH HHSUnited States/ ; U01 CA063464/CA/NCI NIH HHSUnited States/ ; R01 CA132839/CA/NCI NIH HHSUnited States/ ; R01 CA047988/CA/NCI NIH HHSUnited States/ ; R01 CA109767/CA/NCI NIH HHSUnited States/ ; HHSN268201600001C/HL/NHLBI NIH HHSUnited States/ ; Z01 CP010193/ImNIH/Intramural NIH HHSUnited States/ ; R01 HL080467/HL/NHLBI NIH HHSUnited States/ ; UM1 CA167552/CA/NCI NIH HHSUnited States/ ; U01 CA098758/CA/NCI NIH HHSUnited States/ ; R01 CA154823/CA/NCI NIH HHSUnited States/ ; U01 CA182913/CA/NCI NIH HHSUnited States/ ; R01 CA049449/CA/NCI NIH HHSUnited States/ ; R01 CA040360/CA/NCI NIH HHSUnited States/ ; 001/WHO_/World Health OrganizationInternational/ ; R01 CA097075/CA/NCI NIH HHSUnited States/ ; RC1 HL099355/HL/NHLBI NIH HHSUnited States/ ; UM1 CA182883/CA/NCI NIH HHSUnited States/ ; R01 CA097193/CA/NCI NIH HHSUnited States/ ; P30 CA071789/CA/NCI NIH HHSUnited States/ ; U01 CA164973/CA/NCI NIH HHSUnited States/ ; R37 CA054281/CA/NCI NIH HHSUnited States/ ; R01 CA034944/CA/NCI NIH HHSUnited States/ ; HHSN261200800001E/CA/NCI NIH HHSUnited States/ ; R03 CA123546/CA/NCI NIH HHSUnited States/
• Volume:
  80
• Issue:
  18
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:0890dcf637f88821d060a1b5669c8aa93d3876cf7f0ba376336bb91d1dbf40862cd60d68c6c3a60218286378a37b5027dfc78c3ce16983fe73177d75b790fcd4
• Download URL:
  https://stacks.cdc.gov/view/cdc/102178/cdc_102178_DS1.pdf
• File Type:
  [PDF - 414.09 KB ]