Citations 2
Genetically determined body mass index is associated with diffuse large B‐cell lymphoma in polygenic and Mendelian randomization analyses
Moore, Amy , Teras, Lauren R. , Machiela, Mitchell J. , Arias, Joshua , Monnereau, Alain , Wang, Zhaoming , Vermeulen, Roel , Smedby, Karin E. , Spinelli, John J., Nieters, Alexandra , Bracci, Paige M. , Camp, Nicola J. , Hjalgrim, Henrik, Adami, Hans‐Olov , Albanes, Demetrius, Becker, Nikolaus, Benavente, Yolanda , Clavel, Jacqueline , Curtin, Karen , Ghesquières, Hervé, Glimelius, Bengt, Lan, Qing , Liebow, Mark , McKay, James , Offit, Kenneth, Padoan, Marina, Patel, Alpa V. , Ríboli, Elio , Severson, Richard K., Tinker, Lesley F. , Weinstein, Stephanie J. , Zheng, Tongzhang, Chanock, Stephen J., Rothman, Nathaniel , Berndt, Sonja I. , Teras, Lauren R , Wang, Zhaoming , Vajdic, Claire M , De Vivo, Immaculata , Boffetta, Paolo , Brooks-Wilson, Angela R , Canzian, Federico , Southey, Melissa C , Cerhan, James R , Berndt, Sonja I , Clavel, Jacqueline , Machiela, Mitchell J , Riboli, Elio , Kane, Eleanor , Panagiotou, Orestis A. , Doo, Nicole Wong , Slager, Susan L. , Vajdic, Claire M. , Vijai, Joseph , Giles, Graham G. , Link, Brian K. , Arslan, Alan A. , Salles, Gilles , Cozen, Wendy , Vivo, Immaculata De , Albanes, Demetrius , Bisanzi, Simonetta , Brennan, Paul E. , Brooks‐Wilson, Angela , Canzian, Federico , Conde, Lucía , Cox, David G. , Foretová, Lenka , Glimelius, Bengt , Habermann, Thomas M. , Hofmann, Jonathan N. , Lan, Qing , Lincoln, Anne , Maynadié, Marc , Melbye, Mads , Miligi, Lucia , Milne, Roger L. , Molina, Thierry Jo , Morton, Lindsay M. , North, Kari E. , Offit, Kenneth, Piro, Sara , Purdue, Mark P. , Ravichandran, Vignesh , Southey, Melissa C. , Staines, Anthony , Travis, Ruth C. , Wang, Sophia , Weiderpass, Elisabete , Rothman, Nathaniel , Birmann, Brenda M. , Cerhan, James R.
International Journal of Cancer | September 5, 2025 | Volume: 158 | Issue: 1 | Pages: 45-59
Abstract Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry ( N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.
A Recurrent ERCC3 Truncating Mutation Confers Moderate Risk for Breast Cancer
Vijai, Joseph , Topka, Sabine , Villano, Danylo , Ravichandran, Vignesh , Maria, Ann, Gaddam, Pragna, Lincoln, Anne , Kazzaz, Sarah A. , Wenz, Brandon M., Carmi, Shai , Schrader, Kasmintan A. , Hart, Steven N. , Lipkin, Steve M., Walsh, Michael F. , Zhang, Liying , Lejbkowicz, Flavio, Rennert, Hedy S., Weitzel, Jeffrey N. , Daly, Mark J., Nathanson, Katherine L. , Rennert, Gad , Offit, Kenneth , Maxwell, Kara N. , Thomas, Tinu , Neuhausen, Susan L. , Stadler, Zsofia , Robson, Mark E. , Domchek, Susan M. , Couch, Fergus J. , Norton, Larry , Schrader, Intan , Rennert, Gad , Weitzel, Jeffrey N , Joseph, Vijai , Hart, Steven N , Nathanson, Katherine L , Ravichandran, Vignesh , Topka, Sabine
Cancer Discovery | September 21, 2016 | Volume: 6 | Issue: 11 | Pages: 1267-1275
Abstract Known gene mutations account for approximately 50% of the hereditary risk for breast cancer. Moderate and low penetrance variants, discovered by genomic approaches, account for an as-yet-unknown proportion of the remaining heritability. A truncating mutation c.325C>T:p.Arg109* (R109X) in the ATP-dependent helicase ERCC3 was observed recurrently among exomes sequenced in BRCA wild-type, breast cancer–affected individuals of Ashkenazi Jewish ancestry. Modeling of the mutation in ERCC3-deficient or CRISPR/Cas9-edited cell lines showed a consistent pattern of reduced expression of the protein and concomitant hypomorphic functionality when challenged with UVC exposure or treatment with the DNA alkylating agent IlludinS. Overexpressing the mutant protein in ERCC3-deficient cells only partially rescued their DNA repair–deficient phenotype. Comparison of frequency of this recurrent mutation in over 6,500 chromosomes of breast cancer cases and 6,800 Ashkenazi controls showed significant association with breast cancer risk (ORBC = 1.53, ORER+ = 1.73), particularly for the estrogen receptor–positive subset (P < 0.007). Significance: A functionally significant recurrent ERCC3 mutation increased the risk for breast cancer in a genetic isolate. Mutated cell lines showed lower survival after in vitro exposure to DNA-damaging agents. Thus, similar to tumors arising in the background of homologous repair defects, mutations in nucleotide excision repair genes such as ERCC3 could constitute potential therapeutic targets in a subset of hereditary breast cancers. Cancer Discov; 6(11); 1267–75. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 1197