Citations 2
Novel Genetic Risk Loci for Pancreatic Ductal Adenocarcinoma Identified in a Genome-wide Study of African Ancestry Individuals
Ni, Zhanmo , Zhong, Jun , McKean, David, Antwi, Samuel O. , Bracci, Paige M., Du, Mengmeng, Gallinger, Steven, Genkinger, Jeanine, Haiman, Christopher A, Hassan, Manal, Huff, Chad , Kooperberg, Charles, Kastrinos, Fay , LeMarchand, Loic, Lee, WP, Oberg, Ann L. , Park, Margaret A. , Permuth, Jennifer B., Risch, Harvey A., Scheet, Paul , Schwartz, Ann, Shu, Xie, Wolpin, Brian M. , Albanes, Demetrius, Andreotti, Gabriella , Beane-Freeman, Laura, Berndt, Sonja I, Brennan, Paul, Buring, Julie E, Cabrera, Natalia, Campa, Daniele, Chanock, Stephen J, Chung, Charles C., Eliassen, A Heather, Gaziano, J. Michael, Giles, G G, Giovannucci, Edward L, Goggins, Michael, Goodman, Phyllis J. , Hicks, Belynda, Hutchinson, Amy , Jones , Katzke, Verena, Kogevinas, Manolis, Kurtz, Robert C. , Laheru, Daniel, Lee, I, Milne, Roger, Mucci, Lorelei, Patel, Alpa V, Peruchet, Laia, Peters, Ulrike, Porta, Miquel, Rabe, Kari G. , Real, Francisco X, Ricceri, Fulvio, Rothman, Nathaniel, Sesso, Howard D. , Setiawan, Veronica W, Debra, Silverman, Southey, M C, Stampfer, M I, Um, Caroline, Visvanathan, Kala, Wentzensen, Nicolas, Willett, Walter C, Kraft, Peter, Visvanathan, Kala , Zhong, Jun , Zheng, Wei , Canzian, Federico , Malats, Nuria , Duggal, Priya , Klein, Alison P , Chaffee, Kari G. , Antwi, Samuel O , Visvanathan, Kala , Vergara, Candelaria , McKean, David , Connelly, Katelyn E. , Arslan, Alan A. , Bracci, Paige M. , Du, Mengmeng, Genkinger, Jeanine M. , Haiman, Christopher A. , Hung, Rayjean J. , Kooperberg, Charles , Lynch, Shannon M. , Moore, Steven C. , Permuth, Jennifer B. , Risch, Harvey A., Schwartz, Ann, Stolzenberg‐Solomon, Rachael Z. , Zheng, Wei , Albanes, Demetrius , Bamlet, William R. , Berndt, Sonja I. , Brennan, Paul, Buring, Julie E. , Cabrera-Castro, Natalia , Canzian, Federico , Chanock, Stephen Jacob , Chen, Yu , Gaziano, J. Michael , Giovannucci, Edward L. , Goggins, Michael , Hicks, Belynda , Katzke, Verena , Kogevinas, Manolis , Laheru, Daniel A. , Malats, Núria , Milne, Roger, Mucci, Lorelei A. , Neale, Rachel Ε. , Orlow, Irene , Peruchet‐Noray, Laia , Peters, Ulrike , Real, Francisco X. , Ricceri, Fulvio , Rothman, Nathaniel , Setiawan, Veronica Wendy , Silverman, Debra T. , Southey, Melissa C , Stampfer, Meir J. , Tobias, Geoffrey S. , Um, Caroline Y. , Wactawski‐Wende, Jean , Wentzensen, Nicolas , Yu, Kai , Duggal, Priya , Ámundadóttir, Laufey T. , Klein, Alison P.
No container title available | April 23, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Pancreatic cancer disproportionately affects Black individuals in the United States, but they have limited representation in genetic studies of pancreatic ductal adenocarcinoma (PDAC). To address this gap, we performed admixture mapping and genome-wide association analysis (GWAS) in genetically inferred African ancestry individuals (1,030 cases and 889 controls). Admixture mapping identified three regions with a significantly higher proportion of African ancestry in cases compared to controls (5q33.3, 10p1, 22q12.3). GWAS identified a genome-wide significant association at 5p15.33 ( CLPTM1L , rs383009:T>C, T Allele Frequency=0.51, OR:1.45, P value=1.24×10 -8 ), a locus previously associated with PDAC. Known loci at 5p15.33, 7q32.3, 8q24.21 and 7q25.1 also replicated (P value <0.01). Multi-ancestral fine-mapping identified two potential causal SNPs (rs3830069 and rs2735940) at 5p15.33. Collectively these findings identified novel PDAC risk loci and expanded our understanding of this deadly cancer in underrepresented populations, emphasizing the multifactorial nature of PDAC risk including inherited genetic and non-genetic factors. Statement of Significance To understand how genetic variation contributes to PDAC risk in Black people in North American, we studied individuals of genetically-inferred African ancestry. We identified novel risk loci and differences in the contribution of known loci. This demonstrates that ancestry-informed genetic analyses improve our understanding of PDAC risk and enhances discovery.
Genome-Wide Analysis to Assess if Heavy Alcohol Consumption Modifies the Association between SNPs and Pancreatic Cancer Risk
Ni, Zhanmo , Kundu, Prosenjit , McKean, David , Wheeler, William , Albanes, Demetrius , Andreotti, Gabriella , Antwi, Samuel O. , Arslan, Alan A. , Bamlet, William R. , Freeman, Laura E. Beane , Berndt, Sonja I. , Bracci, Paige M. , Brennan, Paul , Buring, Julie E. , Gallinger, Steven , Gaziano, J. Michael , Giovannucci, Edward L. , Goodman, Phyllis J. , Haiman, Christopher A. , Hassan, Manal M. , Holly, Elizabeth A. , Li, Donghui , Oberg, Ann L. , Patel, Alpa V. , Peters, Ulrike , Visvanathan, Kala , White, Emily , Wolpin, Brian M. , Zhong, Jun, McKean, David F , Beane Freeman, Laura E , Chanock, Stephen Jacob , Gallinger, Steven , Gaziano, J Michael , Giles, Graham G , Giovannucci, Edward L , Goggins, Michael G , Goodman, Phyllis J , Haiman, Christopher A , Hassan, Manal M , Holly, Elizabeth A , Hung, Rayjean J , Katzke, Verena , Kooperberg, Charles , Kraft, Peter , Marchand, Loïc Le , Li, Donghui , McCullough, Marjorie L , Milne, Roger L , Moore, Steven C , Neale, Rachel E , Oberg, Ann L , Patel, Alpa V , Peters, Ulrike , Chaffee, Kari G. , Risch, Harvey A , Shu, Xiao-Ou , Smith-Byrne, Karl , Visvanathan, Kala , Wactawski-Wende, Jean , White, Emily , Wolpin, Brian M , Yu, Herbert , Zeleniuch-Jacquotte, Anne , Zheng, Wei , Zhong, Jun , Amundadottir, Laufey , Stolzenberg-Solomon, Rachael , Klein, Alison P , Antwi, Samuel O , Arslan, Alan A , Bamlet, William R , Albanes, Demetrius , Giles, Graham G. , Goggins, Michael , Hung, Rayjean J. , Kooperberg, Charles , Kraft, Peter , Marchand, Loı̈c Le , McCullough, Marjorie L. , Milne, Roger L. , Moore, Steven C. , Neale, Rachel Ε. , Rabe, Kari G. , Risch, Harvey A. , Shu, Xiao‐Ou , Wactawski‐Wende, Jean , Yu, Kai , Zeleniuch‐Jacquotte, Anne , Zheng, Wei , Ámundadóttir, Laufey T. , Stolzenberg‐Solomon, Rachael Z. , Klein, Alison P.
Cancer Epidemiology, Biomarkers & Prevention | June 13, 2024 | Volume: 33 | Issue: 9 | Pages: 1229-1239
Abstract Background: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. Methods: We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case–control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted. Results: A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10−8 in the meta-analysis; Pinteraction = 2.1 × 10−9 in the case–control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004). Conclusions: We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer. Impact: This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.