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201. Supplementary Figure 1 from Common Polymorphisms in the Adiponectin and Its Receptor Genes, Adiponectin Levels and the Risk of Prostate Cancer

Author

Dhillon, Preet K., primary, Penney, Kathryn L., primary, Schumacher, Fredrick, primary, Rider, Jennifer R., primary, Sesso, Howard D., primary, Pollak, Michael, primary, Fiorentino, Michelangelo, primary, Finn, Stephen, primary, Loda, Massimo, primary, Rifai, Nader, primary, Mucci, Lorelei A., primary, Giovannucci, Edward, primary, Stampfer, Meir J., primary, and Ma, Jing, primary

Published
2023
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202. Supplementary Table 2 from Common Polymorphisms in the Adiponectin and Its Receptor Genes, Adiponectin Levels and the Risk of Prostate Cancer

Author

Dhillon, Preet K., primary, Penney, Kathryn L., primary, Schumacher, Fredrick, primary, Rider, Jennifer R., primary, Sesso, Howard D., primary, Pollak, Michael, primary, Fiorentino, Michelangelo, primary, Finn, Stephen, primary, Loda, Massimo, primary, Rifai, Nader, primary, Mucci, Lorelei A., primary, Giovannucci, Edward, primary, Stampfer, Meir J., primary, and Ma, Jing, primary

Published
2023
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203. Figure S2 from Attenuation of SRC Kinase Activity Augments PARP Inhibitor–mediated Synthetic Lethality in BRCA2-altered Prostate Tumors

Author

Chakraborty, Goutam, primary, Patail, Nabeela Khan, primary, Hirani, Rahim, primary, Nandakumar, Subhiksha, primary, Mazzu, Ying Z., primary, Yoshikawa, Yuki, primary, Atiq, Mohammad, primary, Jehane, Lina E., primary, Stopsack, Konrad H., primary, Lee, Gwo-Shu Mary, primary, Abida, Wassim, primary, Morris, Michael J., primary, Mucci, Lorelei A., primary, Danila, Daniel, primary, and Kantoff, Philip W., primary

Published
2023
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204. Supplementary Data from Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell–Level PI3K Pathway Activation

Author

Stopsack, Konrad H., primary, Huang, Ying, primary, Tyekucheva, Svitlana, primary, Gerke, Travis A., primary, Bango, Clyde, primary, Elfandy, Habiba, primary, Bowden, Michaela, primary, Penney, Kathryn L., primary, Roberts, Thomas M., primary, Parmigiani, Giovanni, primary, Kantoff, Philip W., primary, Mucci, Lorelei A., primary, and Loda, Massimo, primary

Published
2023
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205. Supplementary Tables 1, 2, 4 and 5 from The TMPRSS2:ERG Rearrangement, ERG Expression, and Prostate Cancer Outcomes: A Cohort Study and Meta-analysis

Author

Pettersson, Andreas, primary, Graff, Rebecca E., primary, Bauer, Scott R., primary, Pitt, Michael J., primary, Lis, Rosina T., primary, Stack, Edward C., primary, Martin, Neil E., primary, Kunz, Lauren, primary, Penney, Kathryn L., primary, Ligon, Azra H., primary, Suppan, Catherine, primary, Flavin, Richard, primary, Sesso, Howard D., primary, Rider, Jennifer R., primary, Sweeney, Christopher, primary, Stampfer, Meir J., primary, Fiorentino, Michelangelo, primary, Kantoff, Philip W., primary, Sanda, Martin G., primary, Giovannucci, Edward L., primary, Ding, Eric L., primary, Loda, Massimo, primary, and Mucci, Lorelei A., primary

Published
2023
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206. Supplementary Figure from Differences in Prostate Cancer Genomes by Self-reported Race: Contributions of Genetic Ancestry, Modifiable Cancer Risk Factors, and Clinical Factors

Author

Stopsack, Konrad H., primary, Nandakumar, Subhiksha, primary, Arora, Kanika, primary, Nguyen, Bastien, primary, Vasselman, Samantha E., primary, Nweji, Barbara, primary, McBride, Sean M., primary, Morris, Michael J., primary, Rathkopf, Dana E., primary, Slovin, Susan F., primary, Danila, Daniel C., primary, Autio, Karen A., primary, Scher, Howard I., primary, Mucci, Lorelei A., primary, Solit, David B., primary, Gönen, Mithat, primary, Chen, Yu, primary, Berger, Michael F., primary, Schultz, Nikolaus, primary, Abida, Wassim, primary, and Kantoff, Philip W., primary

Published
2023
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207. Data from Common Polymorphisms in the Adiponectin and Its Receptor Genes, Adiponectin Levels and the Risk of Prostate Cancer

Author

Dhillon, Preet K., primary, Penney, Kathryn L., primary, Schumacher, Fredrick, primary, Rider, Jennifer R., primary, Sesso, Howard D., primary, Pollak, Michael, primary, Fiorentino, Michelangelo, primary, Finn, Stephen, primary, Loda, Massimo, primary, Rifai, Nader, primary, Mucci, Lorelei A., primary, Giovannucci, Edward, primary, Stampfer, Meir J., primary, and Ma, Jing, primary

Published
2023
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209. Supplementary Table S1 from Stress-Related Signaling Pathways in Lethal and Nonlethal Prostate Cancer

Author

Lu, Donghao, primary, Sinnott, Jennifer A., primary, Valdimarsdóttir, Unnur, primary, Fang, Fang, primary, Gerke, Travis, primary, Tyekucheva, Svitlana, primary, Fiorentino, Michelangelo, primary, Lambe, Mats, primary, Sesso, Howard D., primary, Sweeney, Christopher J., primary, Wilson, Kathryn M., primary, Giovannucci, Edward L., primary, Loda, Massimo, primary, Mucci, Lorelei A., primary, and Fall, Katja, primary

Published
2023
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210. Supplementary Table 1 from A Single Nucleotide Polymorphism in Inflammatory Gene RNASEL Predicts Outcome after Radiation Therapy for Localized Prostate Cancer

Author

Schoenfeld, Jonathan D., primary, Margalit, Danielle N., primary, Kasperzyk, Julie L., primary, Shui, Irene M., primary, Rider, Jennifer R., primary, Epstein, Mara M., primary, Meisner, Allison, primary, Kenfield, Stacey A., primary, Martin, Neil E., primary, Nguyen, Paul L., primary, Kantoff, Philip W., primary, Giovannucci, Edward L., primary, Stampfer, Meir J., primary, and Mucci, Lorelei A., primary

Published
2023
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213. Data from Genome-wide Association Study of Prostate Cancer Mortality

Author

Penney, Kathryn L., primary, Pyne, Saumyadipta, primary, Schumacher, Fredrick R., primary, Sinnott, Jennifer A., primary, Mucci, Lorelei A., primary, Kraft, Peter L., primary, Ma, Jing, primary, Oh, William K., primary, Kurth, Tobias, primary, Kantoff, Philip W., primary, Giovannucci, Edward L., primary, Stampfer, Meir J., primary, Hunter, David J., primary, and Freedman, Matthew L., primary

Published
2023
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214. Supplementary Figure 1 from A Single Nucleotide Polymorphism in Inflammatory Gene RNASEL Predicts Outcome after Radiation Therapy for Localized Prostate Cancer

Author

Schoenfeld, Jonathan D., primary, Margalit, Danielle N., primary, Kasperzyk, Julie L., primary, Shui, Irene M., primary, Rider, Jennifer R., primary, Epstein, Mara M., primary, Meisner, Allison, primary, Kenfield, Stacey A., primary, Martin, Neil E., primary, Nguyen, Paul L., primary, Kantoff, Philip W., primary, Giovannucci, Edward L., primary, Stampfer, Meir J., primary, and Mucci, Lorelei A., primary

Published
2023
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215. Data from Cholesterol Metabolism and Prostate Cancer Lethality

Author

Stopsack, Konrad H., primary, Gerke, Travis A., primary, Sinnott, Jennifer A., primary, Penney, Kathryn L., primary, Tyekucheva, Svitlana, primary, Sesso, Howard D., primary, Andersson, Swen-Olof, primary, Andrén, Ove, primary, Cerhan, James R., primary, Giovannucci, Edward L., primary, Mucci, Lorelei A., primary, and Rider, Jennifer R., primary

Published
2023
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216. Supplementary Figure S1 from Germline Variants in Asporin Vary by Race, Modulate the Tumor Microenvironment, and Are Differentially Associated with Metastatic Prostate Cancer

Author

Hurley, Paula J., primary, Sundi, Debasish, primary, Shinder, Brian, primary, Simons, Brian W., primary, Hughes, Robert M., primary, Miller, Rebecca M., primary, Benzon, Benjamin, primary, Faraj, Sheila F., primary, Netto, George J., primary, Vergara, Ismael A., primary, Erho, Nicholas, primary, Davicioni, Elai, primary, Karnes, R. Jeffrey, primary, Yan, Guifang, primary, Ewing, Charles, primary, Isaacs, Sarah D., primary, Berman, David M., primary, Rider, Jennifer R., primary, Jordahl, Kristina M., primary, Mucci, Lorelei A., primary, Huang, Jessie, primary, An, Steven S., primary, Park, Ben H., primary, Isaacs, William B., primary, Marchionni, Luigi, primary, Ross, Ashley E., primary, and Schaeffer, Edward M., primary

Published
2023
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217. Supplementary Table 1 from Sleep Duration and Disruption and Prostate Cancer Risk: a 23-Year Prospective Study

Author

Markt, Sarah C., primary, Flynn-Evans, Erin E., primary, Valdimarsdottir, Unnur A., primary, Sigurdardottir, Lara G., primary, Tamimi, Rulla M., primary, Batista, Julie L., primary, Haneuse, Sebastien, primary, Lockley, Steven W., primary, Stampfer, Meir, primary, Wilson, Kathryn M., primary, Czeisler, Charles A., primary, Rider, Jennifer R., primary, and Mucci, Lorelei A., primary

Published
2023
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218. Supplementary Figure 2 from A Single Nucleotide Polymorphism in Inflammatory Gene RNASEL Predicts Outcome after Radiation Therapy for Localized Prostate Cancer

Author

Schoenfeld, Jonathan D., primary, Margalit, Danielle N., primary, Kasperzyk, Julie L., primary, Shui, Irene M., primary, Rider, Jennifer R., primary, Epstein, Mara M., primary, Meisner, Allison, primary, Kenfield, Stacey A., primary, Martin, Neil E., primary, Nguyen, Paul L., primary, Kantoff, Philip W., primary, Giovannucci, Edward L., primary, Stampfer, Meir J., primary, and Mucci, Lorelei A., primary

Published
2023
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219. Supplementary Figure 1 from Cholesterol Metabolism and Prostate Cancer Lethality

Author

Stopsack, Konrad H., primary, Gerke, Travis A., primary, Sinnott, Jennifer A., primary, Penney, Kathryn L., primary, Tyekucheva, Svitlana, primary, Sesso, Howard D., primary, Andersson, Swen-Olof, primary, Andrén, Ove, primary, Cerhan, James R., primary, Giovannucci, Edward L., primary, Mucci, Lorelei A., primary, and Rider, Jennifer R., primary

Published
2023
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221. Supplementary Tables and Figures from Genome-wide Association Study of Prostate Cancer Mortality

Author

Penney, Kathryn L., primary, Pyne, Saumyadipta, primary, Schumacher, Fredrick R., primary, Sinnott, Jennifer A., primary, Mucci, Lorelei A., primary, Kraft, Peter L., primary, Ma, Jing, primary, Oh, William K., primary, Kurth, Tobias, primary, Kantoff, Philip W., primary, Giovannucci, Edward L., primary, Stampfer, Meir J., primary, Hunter, David J., primary, and Freedman, Matthew L., primary

Published
2023
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223. Supplementary Table 1 from Cholesterol Metabolism and Prostate Cancer Lethality

Author

Stopsack, Konrad H., primary, Gerke, Travis A., primary, Sinnott, Jennifer A., primary, Penney, Kathryn L., primary, Tyekucheva, Svitlana, primary, Sesso, Howard D., primary, Andersson, Swen-Olof, primary, Andrén, Ove, primary, Cerhan, James R., primary, Giovannucci, Edward L., primary, Mucci, Lorelei A., primary, and Rider, Jennifer R., primary

Published
2023
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225. Data from Differences in Prostate Cancer Genomes by Self-reported Race: Contributions of Genetic Ancestry, Modifiable Cancer Risk Factors, and Clinical Factors

Author

Stopsack, Konrad H., primary, Nandakumar, Subhiksha, primary, Arora, Kanika, primary, Nguyen, Bastien, primary, Vasselman, Samantha E., primary, Nweji, Barbara, primary, McBride, Sean M., primary, Morris, Michael J., primary, Rathkopf, Dana E., primary, Slovin, Susan F., primary, Danila, Daniel C., primary, Autio, Karen A., primary, Scher, Howard I., primary, Mucci, Lorelei A., primary, Solit, David B., primary, Gönen, Mithat, primary, Chen, Yu, primary, Berger, Michael F., primary, Schultz, Nikolaus, primary, Abida, Wassim, primary, and Kantoff, Philip W., primary

Published
2023
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229. Data from Evaluation of the 8q24 Prostate Cancer Risk Locus and MYC Expression

Author

Pomerantz, Mark M., primary, Beckwith, Christine A., primary, Regan, Meredith M., primary, Wyman, Stacia K., primary, Petrovics, Gyorgy, primary, Chen, Yongmei, primary, Hawksworth, Dorota J., primary, Schumacher, Fredrick R., primary, Mucci, Lorelei, primary, Penney, Kathryn L., primary, Stampfer, Meir J., primary, Chan, Jennifer A., primary, Ardlie, Kristin G., primary, Fritz, Brian R., primary, Parkin, Rachael K., primary, Lin, Daniel W., primary, Dyke, Michelle, primary, Herman, Paula, primary, Lee, Steve, primary, Oh, William K., primary, Kantoff, Philip W., primary, Tewari, Muneesh, primary, McLeod, David G., primary, Srivastava, Shiv, primary, and Freedman, Matthew L., primary

Published
2023
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230. Supplementary Figure 1 from Evaluation of the 8q24 Prostate Cancer Risk Locus and MYC Expression

Author

Pomerantz, Mark M., primary, Beckwith, Christine A., primary, Regan, Meredith M., primary, Wyman, Stacia K., primary, Petrovics, Gyorgy, primary, Chen, Yongmei, primary, Hawksworth, Dorota J., primary, Schumacher, Fredrick R., primary, Mucci, Lorelei, primary, Penney, Kathryn L., primary, Stampfer, Meir J., primary, Chan, Jennifer A., primary, Ardlie, Kristin G., primary, Fritz, Brian R., primary, Parkin, Rachael K., primary, Lin, Daniel W., primary, Dyke, Michelle, primary, Herman, Paula, primary, Lee, Steve, primary, Oh, William K., primary, Kantoff, Philip W., primary, Tewari, Muneesh, primary, McLeod, David G., primary, Srivastava, Shiv, primary, and Freedman, Matthew L., primary

Published
2023
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233. 2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review

Author

Bergengren, Oskar, Pekala, Kelly R., Matsoukas, Konstantina, Fainberg, Jonathan, Mungovan, Sean F., Bratt, Ola, Bray, Freddie, Brawley, Otis, Luckenbaugh, Amy N., Mucci, Lorelei, Morgan, Todd M., Carlsson, Sigrid, V, Bergengren, Oskar, Pekala, Kelly R., Matsoukas, Konstantina, Fainberg, Jonathan, Mungovan, Sean F., Bratt, Ola, Bray, Freddie, Brawley, Otis, Luckenbaugh, Amy N., Mucci, Lorelei, Morgan, Todd M., and Carlsson, Sigrid, V

Abstract

Context: Prostate cancer (PCa) is one of the most common cancers worldwide. Understanding the epidemiology and risk factors of the disease is paramount to improve primary and secondary prevention strategies. Objective: To systematically review and summarize the current evidence on the descrip-tive epidemiology, large screening studies, diagnostic techniques, and risk factors of PCa. Evidence acquisition: PCa incidence and mortality rates for 2020 were obtained from the GLOBOCAN database of the International Agency for Research on Cancer. A systematic search was performed in July 2022 using PubMed/MEDLINE and EMBASE biomedical databases. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered in PROSPERO (CRD42022359728). Evidence synthesis: Globally, PCa is the second most common cancer, with the highest incidence in North and South America, Europe, Australia, and the Caribbean. Risk factors include age, family history, and genetic predisposition. Additional factors may include smoking, diet, physical activity, specific medications, and occupational factors. As PCa screening has become more accepted, newer approaches such as magnetic resonance imaging (MRI) and biomarkers have been implemented to identify patients who are likely to harbor significant tumors. Limitations of this review include the evidence being derived from meta-analyses of mostly retrospective studies. Conclusions: PCa remains the second most common cancer among men worldwide. PCa screening is gaining acceptance and will likely reduce PCa mortality at the cost of over-diagnosis and overtreatment. Increasing use of MRI and biomarkers for the detection of PCa may mitigate some of the negative consequences of screening.

Published
2023
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234. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author

Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., and The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS

Abstract

Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.

Published
2023
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235. Transcriptomes of Prostate Cancer with TMPRSS2:ERG and Other ETS Fusions.

Author

Stopsack, Konrad H, Stopsack, Konrad H, Su, Xiaofeng A, Vaselkiv, J Bailey, Graff, Rebecca E, Ebot, Ericka M, Pettersson, Andreas, Lis, Rosina T, Fiorentino, Michelangelo, Loda, Massimo, Penney, Kathryn L, Lotan, Tamara L, Mucci, Lorelei A, Stopsack, Konrad H, Stopsack, Konrad H, Su, Xiaofeng A, Vaselkiv, J Bailey, Graff, Rebecca E, Ebot, Ericka M, Pettersson, Andreas, Lis, Rosina T, Fiorentino, Michelangelo, Loda, Massimo, Penney, Kathryn L, Lotan, Tamara L, and Mucci, Lorelei A

Abstract

The most common somatic event in primary prostate cancer is a fusion between the androgen-related TMPRSS2 gene and the ERG oncogene. Tumors with these fusions, which occur early in carcinogenesis, have a distinctive etiology. A smaller subset of other tumors harbor fusions between TMPRSS2 and members of the ETS transcription factor family other than ERG. To assess the genomic similarity of tumors with non-ERG ETS fusions and those with fusions involving ERG, this study derived a transcriptomic signature of non-ERG ETS fusions and assessed this signature and ERG-related gene expression in 1,050 men with primary prostate cancer from three independent population-based and hospital-based studies. Although non-ERG ETS fusions involving ETV1, ETV4, ETV5, or FLI1 were individually rare, they jointly accounted for one in seven prostate tumors. Genes differentially regulated between non-ERG ETS tumors and tumors without ETS fusions showed similar differential expression when ERG tumors and tumors without ETS fusions were compared (differences explained: R2 = 69-77%), including ETS-related androgen receptor (AR) target genes. Differences appeared to result from similarities among ETS tumors rather than similarities among non-ETS tumors. Gene sets associated with ERG fusions were consistent with gene sets associated with non-ERG ETS fusions, including fatty acid and amino acid metabolism, an observation that was robust across cohorts.ImplicationsConsidering ETS fusions jointly may be useful for etiologic studies on prostate cancer, given that the transcriptome is profoundly impacted by ERG and non-ERG ETS fusions in a largely similar fashion, most notably genes regulating metabolic pathways.

Published
2023

236. The Impact of PIK3R1 Mutations and Insulin–PI3K–Glycolytic Pathway Regulation in Prostate Cancer

Author

Chakraborty, Goutam, Nandakumar, Subhiksha, Hirani, Rahim, Nguyen, Bastien, Stopsack, Konrad H, Kreitzer, Christoph, Rajanala, Sai Harisha, Ghale, Romina, Mazzu, Ying Z, Pillarsetty, Naga Vara Kishore, Lee, Gwo-Shu Mary, Scher, Howard I, Morris, Michael J, Traina, Tiffany, Razavi, Pedram, Abida, Wassim, Durack, Jeremy C, Solomon, Stephen B, Vander Heiden, Matthew G, Mucci, Lorelei A, Wibmer, Andreas G, Schultz, Nikolaus, Kantoff, Philip W, Chakraborty, Goutam, Nandakumar, Subhiksha, Hirani, Rahim, Nguyen, Bastien, Stopsack, Konrad H, Kreitzer, Christoph, Rajanala, Sai Harisha, Ghale, Romina, Mazzu, Ying Z, Pillarsetty, Naga Vara Kishore, Lee, Gwo-Shu Mary, Scher, Howard I, Morris, Michael J, Traina, Tiffany, Razavi, Pedram, Abida, Wassim, Durack, Jeremy C, Solomon, Stephen B, Vander Heiden, Matthew G, Mucci, Lorelei A, Wibmer, Andreas G, Schultz, Nikolaus, and Kantoff, Philip W

Abstract

Abstract Purpose: Oncogenic alterations of the PI3K/AKT pathway occur in >40% of patients with metastatic castration-resistant prostate cancer, predominantly via PTEN loss. The significance of other PI3K pathway components in prostate cancer is largely unknown. Experimental Design: Patients in this study underwent tumor sequencing using the MSK-IMPACT clinical assay to capture single-nucleotide variants, insertions, and deletions; copy-number alterations; and structural rearrangements, or were profiled through The Cancer Genome Atlas. The association between PIK3R1 alteration/expression and survival was evaluated using univariable and multivariable Cox proportional-hazards regression models. We used the siRNA-based knockdown of PIK3R1 for functional studies. FDG-PET/CT examinations were performed with a hybrid positron emission tomography (PET)/CT scanner for some prostate cancer patients in the MSK-IMPACT cohort. Results: Analyzing 1,417 human prostate cancers, we found a significant enrichment of PIK3R1 alterations in metastatic cancers compared with primary cancers. PIK3R1 alterations or reduced mRNA expression tended to be associated with worse clinical outcomes in prostate cancer, particularly in primary disease, as well as in breast, gastric, and several other cancers. In prostate cancer cell lines, PIK3R1 knockdown resulted in increased cell proliferation and AKT activity, including insulin-stimulated AKT activity. In cell lines and organoids, PIK3R1 loss/mutation was associated with increased sensitivity to AKT inhibitors. PIK3R1-altered patient prostate tumors had increased uptake of the glucose analogue 18F-fluorodeoxyglucose in PET imaging, suggesting increased glycolysis. Conclusions: Our

Published
2023

237. Association between Outdoor Light at Night and Prostate Cancer in the Health Professionals Follow-up Study.

Author

Iyer, Hari, Iyer, Hari, Wilt, Grete, Booker, Benjamin, Nethery, Rachel, Laden, Francine, Mucci, Lorelei, Markt, Sarah, Chowdhury-Paulino, Ilkania, Hart, Jaime, James, Peter, Iyer, Hari, Iyer, Hari, Wilt, Grete, Booker, Benjamin, Nethery, Rachel, Laden, Francine, Mucci, Lorelei, Markt, Sarah, Chowdhury-Paulino, Ilkania, Hart, Jaime, and James, Peter

Abstract

BACKGROUND: Circadian disruption is a potential risk factor for advanced prostate cancer, and light at night (LAN) exposure may disrupt circadian rhythms. We evaluated whether outdoor LAN increases the risk of prostate cancer. METHODS: We prospectively followed 49,148 participants in the Health Professionals Follow-up Study from 1986 through 2016. We estimated baseline and cumulative time-varying outdoor LAN with ∼1 km2 resolution using data from the US Defense Meteorological Satellite Programs Operational Linescan System, which was assigned to participants geocoded addresses. Participants reside in all 50 U.S. states and reported a work or home address. We used multivariable Cox models to estimate HRs and 95% confidence intervals (CI) for the association between outdoor LAN and risk of overall (7,175 cases) and fatal (915 cases) prostate cancer adjusting for individual and contextual factors. RESULTS: There was no association between the interquartile range increase in cumulative LAN and total (HR, 1.02; 95% CI, 0.98-1.06) or fatal (HR, 1.05; 95% CI, 0.96-1.15) prostate cancer in adjusted models. However, there was a positive association between baseline LAN and total prostate cancer among non-movers (HR, 1.06; 95% CI, 1.00-1.14) including among highly screened participants (HR, 1.11; 95% CI, 1.01-1.23). CONCLUSIONS: There was a suggestive positive association between baseline outdoor LAN and total prostate cancer. Additional studies with different measures of outdoor LAN and in more diverse populations are necessary. IMPACT: To our knowledge, this is the first longitudinal cohort study exploring the relationship between outdoor LAN and prostate cancer.

Published
2023

238. Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Author

Darst, Burcu F., Shen, Jiayi, Madduri, Ravi K., Rodriguez, Alexis A., Xiao, Yukai, Sheng, Xin, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Hoffmann, Thomas J., Muir, Kenneth, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne, Wang, Ying, Schleutker, Johanna, MacInnis, Robert J., Cybulski, Cezary, Neal, David E., Nordestgaard, Børge G., Nielsen, Sune F., Batra, Jyotsna, Clements, Judith A., Cancer BioResource, Australian Prostate, Grönberg, Henrik, Pashayan, Nora, Travis, Ruth C., Park, Jong Y., Albanes, Demetrius, Weinstein, Stephanie, Mucci, Lorelei A., Hunter, David J., Penney, Kathryn L., Tangen, Catherine M., Hamilton, Robert J., Parent, Marie Élise, Stanford, Janet L., Koutros, Stella, Wolk, Alicja, Sørensen, Karina D., Blot, William J., Yeboah, Edward D., Mensah, James E., Lu, Yong Jie, Schaid, Daniel J., Thibodeau, Stephen N., West, Catharine M., Maier, Christiane, Kibel, Adam S., Cancel-Tassin, Géraldine, Darst, Burcu F., Shen, Jiayi, Madduri, Ravi K., Rodriguez, Alexis A., Xiao, Yukai, Sheng, Xin, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Hoffmann, Thomas J., Muir, Kenneth, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne, Wang, Ying, Schleutker, Johanna, MacInnis, Robert J., Cybulski, Cezary, Neal, David E., Nordestgaard, Børge G., Nielsen, Sune F., Batra, Jyotsna, Clements, Judith A., Cancer BioResource, Australian Prostate, Grönberg, Henrik, Pashayan, Nora, Travis, Ruth C., Park, Jong Y., Albanes, Demetrius, Weinstein, Stephanie, Mucci, Lorelei A., Hunter, David J., Penney, Kathryn L., Tangen, Catherine M., Hamilton, Robert J., Parent, Marie Élise, Stanford, Janet L., Koutros, Stella, Wolk, Alicja, Sørensen, Karina D., Blot, William J., Yeboah, Edward D., Mensah, James E., Lu, Yong Jie, Schaid, Daniel J., Thibodeau, Stephen N., West, Catharine M., Maier, Christiane, Kibel, Adam S., and Cancel-Tassin, Géraldine

Abstract

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635–0.677) in African and 0.844 (95% CI = 0.840–0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67–2.00) and 2.19 (95% CI = 2.14–2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659–0.700 and AUC = 0.845, 95% CI = 0.841–0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87–2.26 and OR = 2.21, 95% CI = 2.16–2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.

Published
2023

243. Publisher Correction: Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Author

Conti, David V., Darst, Burcu F., Moss, Lilit C., Saunders, Edward J., Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R., Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Sahimi, Ali, Hoffmann, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R., Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Børge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A., Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Jr., Ian M., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L., Ostrander, Elaine A., Geybels, Milan S., Koutros, Stella, Freeman, Laura E. Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Fontham, Elizabeth T. H., Mohler, James, Taylor, Jack A., Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja I., Van Den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, and Haiman, Christopher A.

Published
2021
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245. Brain Cancer

Author

Michaud, Dominique, primary, Savitz, David, additional, and Mucci, Lorelei, additional

Published
2018
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246. Leukemias

Author

Roman, Eve, primary, Smith, Alexandra, additional, and Mucci, Lorelei, additional

Published
2018
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