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Response to Hanif and Sholihah. 对Hanif和Sholihah的回应。
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf226
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
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引用次数: 0
Initial evaluation of a new cervical screening strategy combining human papillomavirus genotyping and automated visual evaluation: the Human Papillomavirus-Automated Visual Evaluation Consortium. 结合人乳头瘤病毒基因分型和自动视觉评估的宫颈筛查新策略的初步评估:人乳头瘤病毒-自动视觉评估联盟
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf054
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.

hpv自动视觉评估(PAVE)联盟正在验证一种子宫颈筛查策略,以便在资源有限的情况下进行准确的子宫颈筛查。一种快速、低成本的HPV检测方法允许对自己收集的阴道标本进行敏感的HPV检测;hpv阴性的妇女放心了。阳性的分类结合HPV基因分型(按癌症风险顺序分为四组)和视觉检查辅助的自动宫颈视觉评估(AVE),将宫颈外观分为严重、不确定或正常。总之,这些组合可以预测哪些女性患有癌前病变,从而对那些最需要治疗的人进行有针对性的治疗。我们分析了来自9个临床站点(巴西、柬埔寨、多米尼加共和国、萨尔瓦多、斯瓦蒂尼、洪都拉斯、马拉维、尼日利亚和坦桑尼亚)的每个PAVE风险水平(通过AVE分类交叉的HPV基因型)的CIN3+产量。来自1832名HPV阳性参与者的数据证实,HPV基因型和AVE分型各自强烈且独立地预测组织学CIN3+的风险。这些低成本测试的组合提供了极好的风险分层,保证了实施前的示范项目。
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引用次数: 0
Response to Yin and Dong. 对阴阳的回应。
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf111
Tanja Stocks, Josef Fritz
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引用次数: 0
Stat Bite: recent trends in colon cancer incidence at ages 25-49 vs 50-74 in 50 countries. Stat Bite: 50个国家25-49岁和50-74岁人群结肠癌发病率的最新趋势。
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf223
Freddie Bray, Mathieu Laversanne
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引用次数: 0
RE: Comparing waist circumference with body mass index on obesity-related cancer risk: a pooled Swedish study. 比较腰围和身体质量指数对肥胖相关癌症风险的影响:一项瑞典的综合研究。
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf110
Shuting Yin, Jie Dong
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引用次数: 0
The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine, and durvalumab: a large, real-life, worldwide population. 分子改变对接受顺铂、吉西他滨和杜伐单抗治疗的晚期胆道癌患者的影响:一个庞大的现实世界人群
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf155
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。
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引用次数: 0
RE: Differential long-term tamoxifen therapy benefit by menopausal status in breast cancer patients: secondary analysis of a controlled randomized clinical trial. 乳腺癌患者绝经后服用他莫昔芬的长期疗效差异:一项对照随机临床试验的二次分析。
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf187
Tong Zhu, Jiawen Bu, Xudong Zhu
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引用次数: 0
RE: Personalized starting age of gastric cancer screening based on individuals' risk profiles: a population-based, prospective study. 基于个体风险概况的胃癌筛查的个性化起始年龄:一项基于人群的前瞻性研究。
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf206
Chunbing Wang, Xiongqi Guo
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引用次数: 0
Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers. 用多祖先多基因风险评分对东亚不吸烟者肺腺癌风险进行分层。
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf272
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.

背景:不吸烟者的肺腺癌(LUAD)是一个主要的公共卫生负担,特别是在东亚妇女中。多基因风险评分(PRSs)在风险分层方面很有前景,但主要是在欧洲血统人群中发展起来的。我们的目的是开发和验证东亚从不吸烟者的单祖先和多祖先PRSs,以改善LUAD风险预测。方法:利用东亚人群(8,002例,20,782例对照)和欧洲人群(2,058例,5,575例对照)的全基因组关联研究汇总统计数据构建PRSs。单祖先模型包括PRS-25、PRS-CT和LDpred2;多祖先模型包括LDpred2+PRS-EUR128、PRS-CSx和CT-SLEB。在女性肺癌协会(FLCCA)的独立东亚数据中进行了评估,并在南京肺癌队列(NJLCC)中进行了外部验证。我们通过AUC、10年和(30-80岁)绝对风险评估来评估预测准确性。结果:利用东亚和欧洲的CT-SLEB(聚类和阈值,超级学习,经验贝叶斯)数据获得的最佳多祖先PRS优于东亚的最佳PRS (LDpred2; AUC = 0.629, 95% CI:0.618,0.641),每SD增加的AUC为0.640 (95% CI: 0.629,0.653),优势比为1.71 (95% CI: 1.61,1.82)。NJLCC验证证实了稳健的性能(AUC =0.649, 95% CI: 0.623, 0.676)。前20%的PRS组的LUAD风险是后20%的3.92倍。此外,前5%的PRS组达到6.69%的终身绝对风险。值得注意的是,该组在41岁时达到了50岁的平均10年LUAD风险(0.42%),提前了9年。结论:多祖先PRS方法增强了东亚不吸烟者的LUAD风险分层,具有一致的外部验证,提示未来的临床应用。
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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}
引用次数: 0
Response to Wang and Guo. 对王和郭的回应。
IF 7.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-01 DOI: 10.1093/jnci/djaf207
Siyi He, Wanqing Chen
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引用次数: 0
期刊
JNCI Journal of the National Cancer Institute
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