Doratha A Byrd, Maria Gomez, Stephanie Hogue, Yunhu Wan, Ana Maria Ortega-Villa, Andrew Warner, Casey Dagnall, Kristine Jones, Belynda Hicks, Paul Albert, Gwen Murphy, Rashmi Sinha, Emily Vogtmann
{"title":"Response to Hanif and Sholihah.","authors":"Doratha A Byrd, Maria Gomez, Stephanie Hogue, Yunhu Wan, Ana Maria Ortega-Villa, Andrew Warner, Casey Dagnall, Kristine Jones, Belynda Hicks, Paul Albert, Gwen Murphy, Rashmi Sinha, Emily Vogtmann","doi":"10.1093/jnci/djaf226","DOIUrl":"10.1093/jnci/djaf226","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"2144-2145"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian Befano, Jayashree Kalpathy-Cramer, Didem Egemen, Federica Inturrisi, José Jeronimo, Ana Cecilia Rodríguez, Nicole Campos, Miriam Cremer, Ana Ribeiro, Kayode Olusegun Ajenifuja, Andrew Goldstein, Amna Haider, Karen Yeates, Margaret Madeleine, Teresa Norris, Jacqueline Figueroa, Karla Alfaro, Tainá Raiol, Clement Adepiti, Judith Norman, George Kassim Chilinda, Bariki Mchome, Yeycy Donastorg, Xolisile Dlamini, Gabriel Conzuelo, Adekunbiola A Banjo, Pauline Chone, Alex Mremi, Arismendy Benitez, Zeev Rosberger, Te Vantha, Ignacio Prieto-Egido, Jen Boyd-Morin, Christopher Clark, Scott Kinder, Nicolas Wentzensen, Kanan Desai, Rebecca Perkins, Silvia de Sanjosé, Mark Schiffman
The HPV-Automated Visual Evaluation Consortium is validating a cervical screening strategy enabling accurate cervical screening in resource-limited settings. A rapid, low-cost human papillomavirus (HPV) assay permits sensitive HPV testing of self-collected vaginal specimens; HPV-negative women are reassured. Triage of positive participants combines HPV genotyping (4 groups in order of cancer risk) and visual inspection assisted by automated cervical visual evaluation that classifies cervical appearance as severe, indeterminate, or normal. Together, the combination predicts which women have precancer, permitting targeted management to those most needing treatment. We analyzed CIN3+ yield for each HPV-Automated Visual Evaluation risk level (HPV genotype crossed by automated cervical visual evaluation classification) from 9 clinical sites (Brazil, Cambodia, Dominican Republic, El Salvador, Eswatini, Honduras, Malawi, Nigeria, and Tanzania). Data from 1832 HPV-positive participants confirmed that HPV genotype and automated cervical visual evaluation classification strongly and independently predict risk of histologic CIN3+. The combination of these low-cost tests provided excellent risk stratification, warranting pre-implementation demonstration projects.
{"title":"Initial evaluation of a new cervical screening strategy combining human papillomavirus genotyping and automated visual evaluation: the Human Papillomavirus-Automated Visual Evaluation Consortium.","authors":"Brian Befano, Jayashree Kalpathy-Cramer, Didem Egemen, Federica Inturrisi, José Jeronimo, Ana Cecilia Rodríguez, Nicole Campos, Miriam Cremer, Ana Ribeiro, Kayode Olusegun Ajenifuja, Andrew Goldstein, Amna Haider, Karen Yeates, Margaret Madeleine, Teresa Norris, Jacqueline Figueroa, Karla Alfaro, Tainá Raiol, Clement Adepiti, Judith Norman, George Kassim Chilinda, Bariki Mchome, Yeycy Donastorg, Xolisile Dlamini, Gabriel Conzuelo, Adekunbiola A Banjo, Pauline Chone, Alex Mremi, Arismendy Benitez, Zeev Rosberger, Te Vantha, Ignacio Prieto-Egido, Jen Boyd-Morin, Christopher Clark, Scott Kinder, Nicolas Wentzensen, Kanan Desai, Rebecca Perkins, Silvia de Sanjosé, Mark Schiffman","doi":"10.1093/jnci/djaf054","DOIUrl":"10.1093/jnci/djaf054","url":null,"abstract":"<p><p>The HPV-Automated Visual Evaluation Consortium is validating a cervical screening strategy enabling accurate cervical screening in resource-limited settings. A rapid, low-cost human papillomavirus (HPV) assay permits sensitive HPV testing of self-collected vaginal specimens; HPV-negative women are reassured. Triage of positive participants combines HPV genotyping (4 groups in order of cancer risk) and visual inspection assisted by automated cervical visual evaluation that classifies cervical appearance as severe, indeterminate, or normal. Together, the combination predicts which women have precancer, permitting targeted management to those most needing treatment. We analyzed CIN3+ yield for each HPV-Automated Visual Evaluation risk level (HPV genotype crossed by automated cervical visual evaluation classification) from 9 clinical sites (Brazil, Cambodia, Dominican Republic, El Salvador, Eswatini, Honduras, Malawi, Nigeria, and Tanzania). Data from 1832 HPV-positive participants confirmed that HPV genotype and automated cervical visual evaluation classification strongly and independently predict risk of histologic CIN3+. The combination of these low-cost tests provided excellent risk stratification, warranting pre-implementation demonstration projects.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"2124-2129"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to Yin and Dong.","authors":"Tanja Stocks, Josef Fritz","doi":"10.1093/jnci/djaf111","DOIUrl":"10.1093/jnci/djaf111","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"2132-2133"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stat Bite: recent trends in colon cancer incidence at ages 25-49 vs 50-74 in 50 countries.","authors":"Freddie Bray, Mathieu Laversanne","doi":"10.1093/jnci/djaf223","DOIUrl":"10.1093/jnci/djaf223","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":"117 10","pages":"2146-2147"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RE: Comparing waist circumference with body mass index on obesity-related cancer risk: a pooled Swedish study.","authors":"Shuting Yin, Jie Dong","doi":"10.1093/jnci/djaf110","DOIUrl":"10.1093/jnci/djaf110","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"2130-2131"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Margherita Rimini, Lorenzo Fornaro, Federica Lo Prinzi, Mario Domenico Rizzato, Anna Saborowski, Lorenzo Antonuzzo, Federico Rossari, Tomoyuki Satake, Frederik Peeters, Caterina Vivaldi, Tiziana Pressiani, Jessica Lucchetti, Jin Won Kim, Oluseyi Abidoye, Ilario Giovanni Rapposelli, Stefano Tamberi, Fabian Finkelmeier, Guido Giordano, Federico Nichetti, Hong Jae Chon, Chiara Braconi, Aitzaz Qaisar, Chiara Pirrone, Florian Castet, Emiliano Tamburini, Changhoon Yoo, Alessandro Parisi, Anna Diana, Mario Scartozzi, Gerald W Prager, Antonio Avallone, Salvatore Corallo, Marta Schirripa, Il Hwan Kim, Lukas Perkhofer, Ester Oneda, Monica Verrico, Jorge Adeva, Stephen L Chan, Gian Paolo Spinelli, Nicola Personeni, Ingrid Garajova, Maria Grazia Rodriquenz, Silvana Leo, Cecilia Melo Alvim, Ricardo Roque, Giovanni Farinea, Francesca Salani, Antonio De Rosa, Daniele Lavacchi, Silvia Camera, Masafumi Ikeda, Jeroen Dekervel, Monica Niger, Rita Balsano, Giuseppe Tonini, Minsu Kang, Tanios Bekaii-Saab, Luca Esposito, Alessandra Boccaccino, Vera Himmelsbach, Matteo Landriscina, Selma Ahcene Djaballah, Valentina Zanuso, Umberto Malapelle, Francesco Pepe, Gianluca Masi, Arndt Vogel, Sara Lonardi, Lorenza Rimassa, Andrea Casadei-Gardini
Background: Cisplatin, gemcitabine, and durvalumab combination is a standard first-line treatment for advanced biliary tract cancer. This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced biliary tract cancer treated with cisplatin, gemcitabine, and durvalumab in real-world clinical practice.
Methods: Patients with unresectable, locally advanced, or metastatic biliary tract cancer treated with cisplatin and gemcitabine plus durvalumab across 39 centers in 11 countries in Europe, the United States, and Asia were included in this analysis.
Results: The cohort included 513 patients with advanced biliary tract cancer. The 5 most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (hazard ratio [HR] = 0.49, P = .018) and overall survival (HR = 0.11, P = .023), while TP53 mutations were linked to worse PFS (HR = 1.62, P = .0047) and TERT mutations to worse overall survival (HR = 8.92, P = .0012). No other genomic alterations were statistically associated with outcomes. Subgroup analysis showed that TP53 mutations negatively affected PFS and overall survival in intrahepatic cholangiocarcinoma, while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma. No gene alterations were linked to outcomes in gallbladder cancer.
Conclusions: This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and overall survival and highlights the negative prognostic roles of TP53 (PFS) and TERT (overall survival) mutations, providing valuable insights for personalized treatment strategies in biliary tract cancer.
背景与目的:顺铂、吉西他滨和杜伐单抗(CGD)联合治疗是晚期胆道癌(BTC)的标准一线治疗方案。本研究旨在评估在现实世界的临床实践中,基因改变对晚期BTC患者接受CGD治疗的结果的影响。方法:来自11个国家(欧洲、美国和亚洲)39个中心的不可切除、局部晚期或转移性BTC患者接受CGD治疗,纳入本分析。结果:该队列包括513例晚期BTC患者。最常发生改变的5个基因是TP53(22.1%)、KRAS(13.7%)、CDKN2A/B(13.6%)、ARID1A(12.2%)和IDH1(9.2%)。在多变量分析中,SMAD4突变与改善的无进展生存期(PFS) (HR 0.49, p = 0.018)和总生存期(OS) (HR 0.11, p = 0.023)相关,而TP53突变与恶化的PFS (HR 1.62, p = 0.0047)和TERT突变与恶化的OS (HR 8.92, p = 0.0012)相关。没有其他基因组改变与结果显著相关。亚组分析显示,TP53突变对肝内胆管癌(iCCA)的PFS和OS有负面影响,而KRAS突变与肝外胆管癌(eCCA)的PFS较差相关。没有基因改变与胆囊癌的预后有关。结论:通过全面的分子分析,这项大规模分析支持SMAD4突变对PFS和OS的积极预后影响,并强调了TP53 (PFS)和TERT (OS)突变的负面预后作用,为BTC的个性化治疗策略提供了有价值的见解。
{"title":"The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine, and durvalumab: a large, real-life, worldwide population.","authors":"Margherita Rimini, Lorenzo Fornaro, Federica Lo Prinzi, Mario Domenico Rizzato, Anna Saborowski, Lorenzo Antonuzzo, Federico Rossari, Tomoyuki Satake, Frederik Peeters, Caterina Vivaldi, Tiziana Pressiani, Jessica Lucchetti, Jin Won Kim, Oluseyi Abidoye, Ilario Giovanni Rapposelli, Stefano Tamberi, Fabian Finkelmeier, Guido Giordano, Federico Nichetti, Hong Jae Chon, Chiara Braconi, Aitzaz Qaisar, Chiara Pirrone, Florian Castet, Emiliano Tamburini, Changhoon Yoo, Alessandro Parisi, Anna Diana, Mario Scartozzi, Gerald W Prager, Antonio Avallone, Salvatore Corallo, Marta Schirripa, Il Hwan Kim, Lukas Perkhofer, Ester Oneda, Monica Verrico, Jorge Adeva, Stephen L Chan, Gian Paolo Spinelli, Nicola Personeni, Ingrid Garajova, Maria Grazia Rodriquenz, Silvana Leo, Cecilia Melo Alvim, Ricardo Roque, Giovanni Farinea, Francesca Salani, Antonio De Rosa, Daniele Lavacchi, Silvia Camera, Masafumi Ikeda, Jeroen Dekervel, Monica Niger, Rita Balsano, Giuseppe Tonini, Minsu Kang, Tanios Bekaii-Saab, Luca Esposito, Alessandra Boccaccino, Vera Himmelsbach, Matteo Landriscina, Selma Ahcene Djaballah, Valentina Zanuso, Umberto Malapelle, Francesco Pepe, Gianluca Masi, Arndt Vogel, Sara Lonardi, Lorenza Rimassa, Andrea Casadei-Gardini","doi":"10.1093/jnci/djaf155","DOIUrl":"10.1093/jnci/djaf155","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin, gemcitabine, and durvalumab combination is a standard first-line treatment for advanced biliary tract cancer. This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced biliary tract cancer treated with cisplatin, gemcitabine, and durvalumab in real-world clinical practice.</p><p><strong>Methods: </strong>Patients with unresectable, locally advanced, or metastatic biliary tract cancer treated with cisplatin and gemcitabine plus durvalumab across 39 centers in 11 countries in Europe, the United States, and Asia were included in this analysis.</p><p><strong>Results: </strong>The cohort included 513 patients with advanced biliary tract cancer. The 5 most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (hazard ratio [HR] = 0.49, P = .018) and overall survival (HR = 0.11, P = .023), while TP53 mutations were linked to worse PFS (HR = 1.62, P = .0047) and TERT mutations to worse overall survival (HR = 8.92, P = .0012). No other genomic alterations were statistically associated with outcomes. Subgroup analysis showed that TP53 mutations negatively affected PFS and overall survival in intrahepatic cholangiocarcinoma, while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma. No gene alterations were linked to outcomes in gallbladder cancer.</p><p><strong>Conclusions: </strong>This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and overall survival and highlights the negative prognostic roles of TP53 (PFS) and TERT (overall survival) mutations, providing valuable insights for personalized treatment strategies in biliary tract cancer.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"2029-2043"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RE: Differential long-term tamoxifen therapy benefit by menopausal status in breast cancer patients: secondary analysis of a controlled randomized clinical trial.","authors":"Tong Zhu, Jiawen Bu, Xudong Zhu","doi":"10.1093/jnci/djaf187","DOIUrl":"10.1093/jnci/djaf187","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"2134-2135"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RE: Personalized starting age of gastric cancer screening based on individuals' risk profiles: a population-based, prospective study.","authors":"Chunbing Wang, Xiongqi Guo","doi":"10.1093/jnci/djaf206","DOIUrl":"10.1093/jnci/djaf206","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"2138-2139"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Batel Blechter, Xiaoyu Wang, Juncheng Dai, Christiana Karsonaki, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Parichoy Pal Choudhury, Jacob Williams, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Yy Wong Sm, Min-Ho Shin, Lap Ping Chung, Yang Yang, Hong Zheng, Hongji Dai, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Yataro Daigo, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, H Dean Hosgood, Hideo Kunitoh, Shun-Ichi Watanabe, Yohei Miyagi, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Mitchell J Machiela, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Kuan-Yu Chen, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Yu-Tang Gao, Jianjun Liu, Ann G Schwartz, Richard Houlston, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, James McKay, John K Field, Michael P A Davies, Sanjay S Shete, Loïc Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Chung-Hsing Chen, Chin-Fu Hsiao, Zhibin Hu, Laura Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Yi Young Choi, In Kyu Park, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Fang-Yu Tsai, John K C Chan, Jihua Li, Hsien-Chih Lin, Jie Liu, Bao Song, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Hongxia Ma, Meng Zhu, Yifan Wang, Tianchen Qi, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen ScD, Pan-Chyr Yang, Victoria L Stevens, Joseph F Fraumeni, Kuang Lin, Robin G Walters, Zhengming Chen, Nilanjan Chatterjee, Olga Y Gorlova, Christopher I Amos, Hongbing Shen, Chao Agnes Hsiung, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan, Haoyu Zhang
Background: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.
Methods: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates.
Results: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC = 0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI : 0.629,0.653) and odds ratio of 1.71 (95% CI : 1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier.
Conclusions: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.
{"title":"Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers.","authors":"Batel Blechter, Xiaoyu Wang, Juncheng Dai, Christiana Karsonaki, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Parichoy Pal Choudhury, Jacob Williams, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Yy Wong Sm, Min-Ho Shin, Lap Ping Chung, Yang Yang, Hong Zheng, Hongji Dai, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Yataro Daigo, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, H Dean Hosgood, Hideo Kunitoh, Shun-Ichi Watanabe, Yohei Miyagi, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Mitchell J Machiela, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Kuan-Yu Chen, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Yu-Tang Gao, Jianjun Liu, Ann G Schwartz, Richard Houlston, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, James McKay, John K Field, Michael P A Davies, Sanjay S Shete, Loïc Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Chung-Hsing Chen, Chin-Fu Hsiao, Zhibin Hu, Laura Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Yi Young Choi, In Kyu Park, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Fang-Yu Tsai, John K C Chan, Jihua Li, Hsien-Chih Lin, Jie Liu, Bao Song, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Hongxia Ma, Meng Zhu, Yifan Wang, Tianchen Qi, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen ScD, Pan-Chyr Yang, Victoria L Stevens, Joseph F Fraumeni, Kuang Lin, Robin G Walters, Zhengming Chen, Nilanjan Chatterjee, Olga Y Gorlova, Christopher I Amos, Hongbing Shen, Chao Agnes Hsiung, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan, Haoyu Zhang","doi":"10.1093/jnci/djaf272","DOIUrl":"10.1093/jnci/djaf272","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.</p><p><strong>Methods: </strong>PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates.</p><p><strong>Results: </strong>The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC = 0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI : 0.629,0.653) and odds ratio of 1.71 (95% CI : 1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier.</p><p><strong>Conclusions: </strong>Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to Wang and Guo.","authors":"Siyi He, Wanqing Chen","doi":"10.1093/jnci/djaf207","DOIUrl":"10.1093/jnci/djaf207","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"2140-2141"},"PeriodicalIF":7.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}