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.
HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
Wang, Sophia , Carrington, Mary , Berndt, Sonja I. , Bracci, Paige M. , Smedby, Karin E. , Hjalgrim, Henrik , Vijai, Joseph , Morton, Lindsay M. , Vermeulen, Roel , Paltiel, Ora , Vajdic, Claire M. , Linet, Martha S. , Nieters, Alexandra , Sanjosé, Sílvia de, Brown, Elizabeth E. , Turner, Jennifer , Spinelli, John J., Zheng, Tongzhang, Birmann, Brenda M. , Flowers, Christopher R. , Becker, Nikolaus, Holly, Elizabeth A., Kane, Eleanor , Weisenburger, Dennis D. , Cocco, Pierluigi, Weinstein, Stephanie J. , Diver, W. Ryan , Lax, S. , Travis, Ruth C., Kaaks, Rudolph, Ríboli, Elio , Benavente, Yolanda , Brennan, Paul, McKay, James , Delfau‐Larue, Marie‐Hélène , Link, Brian K. , Magnani, Corrado , Latte, Giancarlo, Doo, Nicole Wong , Offit, Kenneth , Musinsky, Jacob, Arslan, Alan A. , Purdue, Mark P. , Adami, Hans‐Olov , Melbye, Mads , Glimelius, Bengt , Conde, Lucía , Camp, Nicola J. , Glenn, Martha, Curtin, Karen , Clavel, Jacqueline , Monnereau, Alain, Cox, David G. , Ghesquières, Hervé , Salles, Gilles , Bofetta, Paulo, Foretová, Lenka , Staines, Anthony , Davis, S. Scott , Severson, Richard K., Lan, Qing , Brooks‐Wilson, Angela , Smith, Martyn T. , Roman, Eve , Kricker, Anne , Zhang, Yawei , Kraft, Peter , Rothman, Nathaniel , Hartge, Patricia, Skibola, Christine F., Cocco, Pierluigi , Travis, Ruth C. , Monnereau, Alain , Turner, Jennifer , Weinstein, Stephanie J , Link, Brian K , Joseph, Vijai , Cocco, Pierluigi , Brooks-Wilson, Angela R , Vajdic, Claire M , Kane, Eleanor , Arslan, Alan A , Travis, Ruth C , Kraft, Peter , Morton, Lindsay M , Salles, Gilles A , Wang, Sophia S , Birmann, Brenda M , Roman, Eve , Clavel, Jacqueline , Riboli, Elio , Slager, Susan L. , Voutsinas, Jenna M. , Cerhan, James R. , Cozen, Wendy , Maynadié, Marc , Albanes, Demetrius , Teras, Lauren R. , Ennas, Maria Grazia , Feldman, Andrew L. , Giles, Graham G. , Southey, Melissa C. , Milne, Roger L. , Chanock, Stephen Jacob , Doo, Nicole Wong
Cancer Research | May 7, 2018 | Volume: 78 | Issue: 14 | Pages: 4086-4096
Abstract A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.