Rothman, Nathaniel
Mayo Clinic
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Citations 2
A Prognostic Signature for Lung Adenocarcinoma in Patients Who Have Never Smoked
Wei, Zhao , Zhang, Tongwu , Hua, Xing , Hoang, Phuc H. , Miraftab, Mona , Saha, Monjoy , McElderry, John, Sang, Jian , Lee, Olivia W. , Hartman, Caleb , Sharma, Sunandini , Colón-Matos, Frank J. , Anyaso‐Samuel, Samuel , Hutchinson, Amy , Hicks, Belynda , Rosenbaum, Jennifer, Zhong, Xiaoming , Yang, Yang , Leung, Kin Chung, Wong, Maria Pik , Mańczuk, Marta , Shangina, Oxana , Заридзе, Давид , Milosavljević, Saša , Ognjanovic, Simona , Savić, Milan , Gaborieau, Valérie , Brennan, Paul , Edell, Eric S. , Más, Luís , Chen, Chih‐Yi , Chang, I‐Shou , Hsiung, Chao A. , Liu, Geoffrey , Santamaría, Juan Miguel , Mutreja, Karun , Rothman, Nathaniel , Leduc, Charles , Sholl, Lynette M. , Lan, Qing , Yang, Lixing , Shi, Jianxin , Landi, Maria Teresa , Zhao, Wei , McElderry, John P , Khandekar, Azhar , Sharma, Sunandini , Colón-Matos, Frank J , Anyaso-Samuel, Samuel , Wang, Difei , Jones, Kristine , Hutchinson, Amy , Hicks, Belynda , Rosenbaum, Jennifer , Zhong, Xiaoming , Yang, Yang , Pesatori, Angela C , Consonni, Dario , Christiani, David C. , Leung, Kin Chung , Wong, Maria Pik , Manczuk, Marta , Lissowska, Jolanta , Świątkowska, Beata , Mukeria, Anush , Shangina, Oxana , Zaridze, David , Holcatova, Ivana , Mates, Dana , Milosavljevic, Sasa , Ognjanovic, Simona , Savic, Milan , Kontic, Milica , Gaborieau, Valerie , Brennan, Paul , Arrieta, Oscar , Bossé, Yohan , Schabath, Matthew B , Hofman, Paul , Mas, Luis , Yendamuri, Sai S , Chen, Chih-Yi , Chang, I-Shou , Hsiung, Chao Agnes , Liu, Geoffrey , Martinez Santamaría, Jacobo , Gould Rothberg, Bonnie E , Mutreja, Karun , Lawrence, Scott M. , Rothman, Nathaniel , Alexandrov, Ludmil B , Leduc, Charles , Baine, Marina K , Joubert, Philippe , Sholl, Lynette , Travis, William D , Homer, Robert , Lan, Qing , Chanock, Stephen Jacob , Yang, Lixing , Yang, Soo-Ryum , Shi, Jianxin , Landi, Maria T , Lissowska, Jolanta , Świątkowska, Beata , Holcátová, Ivana , Mateș, Dana , Arrieta, Óscar , Bossé, Yohan , Schabath, Matthew B. , Alexandrov, Ludmil B. , Travis, William D. , Homer, Robert
Cancer Discovery | October 30, 2025 | Volume: 16 | Issue: 3 | Pages: 460-477
Abstract Understanding tumor cell dynamics can improve prognosis and treatment but remains limited for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA sequencing data from 684 NS-LUAD cases and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histologic data further characterized the subtypes. “Steady,” marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver gene alterations, is linked to prolonged survival and low immune evasion. “Proliferative” shows high proliferation markers, TP53 mutations, and gene fusions. “Chaotic,” with high epithelial-to-mesenchymal transition markers, has the worst prognosis, even within stage I tumors. Lacking known molecular or histologic characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the classification and predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving early-stage NS-LUAD prognostication in clinical settings. Significance: The transcriptome of 684 NS-LUAD identifies three subtypes with different cellular dynamics and genomic and morphologic features. A 60-gene signature accurately stratifies subjects for mortality risk, even in stage I, offering a potential clinically applicable tool for treatment decision-making in patients with NS-LUAD. See related commentary by Azizi et al., p. 423
Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization
King, Sontoria D. , Veliginti, Swathi , Brouwers, Martijn C.G.J. , Ren, Zhewen , Zheng, Wei , Setiawan, Veronica Wendy , Wilkens, Lynne R. , Shu, Xiao‐Ou , Arslan, Alan A. , Freeman, Laura E. Beane , Bracci, Paige M. , Du, Mengmeng , Gallinger, Steven , Goodman, Phyllis J. , Haiman, Christopher A. , Visvanathan, Kala , White, Emily , Andreotti, Gabriella , Babić, Ana , Berndt, Sonja I. , Brennan, Paul , Buring, Julie E. , Fuchs, Charles S. , Gaziano, J. Michael , Giovannucci, Edward L. , Hackert, Thilo , Hassan, Manal M. , Kurtz, Robert C. , Lee, I‐Min , Oberg, Ann L. , Porta, Miquel , Rothman, Nathaniel , Sesso, Howard D. , Wentzensen, Nicolas , Yu, Kai , Wolpin, Brian M. , Li, Donghui , Patel, Alpa V. , Peters, Ulrike , Ríboli, Elio , Zhong, Jun, Antwi, Samuel O. , Zhong, Jun , Setiawan, Veronica W , Beane Freeman, Laura E , Canzian, Federico , Du, Mengmeng , Gallinger, Steven , Giles, Graham G , Goodman, Phyllis J , Haiman, Christopher A , Kogevinas, Manolis , Kooperberg, Charles , Marchand, Loïc Le , Neale, Rachel E , Visvanathan, Kala , White, Emily , Albanes, Demetrius , Andreotti, Gabriella , Babic, Ana , Berndt, Sonja I , Brais, Lauren K , Brennan, Paul , Buring, Julie E , Chaffee, Kari G. , Bamlet, William R , Chanock, Stephen Jacob , Fuchs, Charles S , Gaziano, J Michael , Giovannucci, Edward L , Hackert, Thilo , Hassan, Manal M , Katzke, Verena , Kurtz, Robert C , Lee, I-Min , Malats, Nuria , Murphy, Neil , Oberg, Ann L , Orlow, Irene , Porta, Miquel , Real, Francisco X , Rothman, Nathaniel , Sesso, Howard D , Silverman, Debra T. , Thompson, Ian M , Wactawski-Wende, Jean , Wang, Xiaoliang , Wentzensen, Nicolas , Yu, Herbert , Zeleniuch-Jacquotte, Anne , Yu, Kai , Wolpin, Brian M , Duell, Eric J , Li, Donghui , Hung, Rayjean J , Perdomo, Sandra , McCullough, Marjorie L , Freedman, Neal D , Patel, Alpa V , Peters, Ulrike , Riboli, Elio , Sund, Malin , Tjønneland, Anne , Zhong, Jun , Van Den Eeden, Stephen K , Kraft, Peter , Risch, Harvey A , Amundadottir, Laufey , Klein, Alison P , Stolzenberg-Solomon, Rachael , Antwi, Samuel O , Arslan, Alan A , Shu, Xiao-Ou , Zheng, Wei , Wilkens, Lynne R , Canzian, Federico , Giles, Graham G. , Kooperberg, Charles , Marchand, Loı̈c Le , Neale, Rachel Ε. , Albanes, Demetrius , Rabe, Kari G. , Bamlet, William R. , Malats, Núria , Murphy, Neil , Orlow, Irene , Real, Francisco X. , Thompson, Ian M. , Wactawski‐Wende, Jean , Wang, Xiaoliang , Yu, Kai , Zeleniuch‐Jacquotte, Anne , Duell, Eric J. , Hung, Rayjean J. , McCullough, Marjorie L. , Freedman, Neal D. , Sund, Malin , Tjønneland, Anne , Kraft, Peter , Risch, Harvey A. , Ámundadóttir, Laufey T. , Klein, Alison P. , Stolzenberg‐Solomon, Rachael Z.
Cancer Epidemiology, Biomarkers & Prevention | June 24, 2023 | Volume: 32 | Issue: 9 | Pages: 1265-1269
Abstract Background: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. Methods: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes. Results: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88–1.22; MR-Egger OR, 0.89; 95% CI, 0.65–1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90–1.27; MR-Egger OR, 0.93; 95% CI, 0.67–1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample. Conclusions: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk. Impact: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.