Journal of Thoracic Oncology最新文献

{"title":"Lung Cancer Screening and Early Detection Terminology: Time to Sing From the Same Song Sheet.","authors":"Betty C Tong, Thomas E Stinchcombe","doi":"10.1016/j.jtho.2024.09.1384","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.09.1384","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"1589-1590"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791994","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":"Second Primary Lung Cancer-Potential Areas of Ambiguity.","authors":"Sarah Østrup Jensen, David A Moore, Arif A Surani, Philip A J Crosbie, Nitzan Rosenfeld, Robert C Rintoul","doi":"10.1016/j.jtho.2024.09.1432","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.09.1432","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"e101-e102"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792055","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":"Lung-MAP Next-Generation Sequencing Analysis of Advanced Squamous Cell Lung Cancers (SWOG S1400).","authors":"David Kozono, Xing Hua, Michael C Wu, Khaled A Tolba, Saiama N Waqar, Konstantin H Dragnev, Haiying Cheng, Fred R Hirsch, Philip C Mack, Jhanelle E Gray, Karen Kelly, Hossein Borghaei, Roy S Herbst, David R Gandara, Mary W Redman","doi":"10.1016/j.jtho.2024.07.024","DOIUrl":"10.1016/j.jtho.2024.07.024","url":null,"abstract":"<p><strong>Introduction: </strong>Squamous cell cancer (SqCC) is a lung cancer subtype with few targeted therapy options. Molecular characterization, that is, by next-generation sequencing (NGS), is needed to identify potential targets. Lung Cancer Master Protocol Southwest Oncology Group S1400 enrolled patients with previously treated stage IV or recurrent SqCC to assess NGS biomarkers for therapeutic sub-studies.</p><p><strong>Methods: </strong>Tumors underwent NGS using Foundation Medicine's FoundationOne research platform, which sequenced the exons and/or introns of 313 cancer-related genes. Mutually exclusive gene set analysis and Selected Events Linked by Evolutionary Conditions across Human Tumors were performed to identify mutually exclusive and co-occurring gene alterations. Comparisons were performed with data on 495 lung SqCC downloaded from The Cancer Genome Atlas. Cox proportional hazards models were used to assess associations between genetic variants and survival.</p><p><strong>Results: </strong>NGS data are reported for 1672 patients enrolled on S1400 between 2014 and 2019. Mutually exclusive gene set analysis identified two non-overlapping sets of mutually exclusive alterations with a false discovery rate of less than 15%: NFE2L2, KEAP1, and PARP4; and CDKN2A and RB1. PARP4, a relatively uncharacterized gene, showed three frequent mutations suggesting functional significance: 3116T>C (I1039T), 3176A>G (Q1059R), and 3509C>T (T1170I). When taken together, NFE2L2 and KEAP1 alterations were associated with poorer survival.</p><p><strong>Conclusions: </strong>As the largest dataset to date of lung SqCC profiled on a clinical trial, the S1400 NGS dataset establishes a rich resource for biomarker discovery. Mutual exclusivity of PARP4 and NFE2L2 or KEAP1 alterations suggests that PARP4 may have an uncharacterized role in a key pathway known to impact oxidative stress response and treatment resistance.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":"1618-1629"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902159","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":"Commentary on \"Evaluation of Major Pathologic Response and Pathologic Complete Response as Surrogate End Points for Survival in Randomized Controlled Trials of Neoadjuvant Immune Checkpoint Blockade in Resectable in NSCLC\".","authors":"Robert B Cameron, Jacobi B Hines, Valter Torri, Marina C Garassino","doi":"10.1016/j.jtho.2024.09.1424","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.09.1424","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"e80-e81"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791982","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":"Second Primary Lung Cancer-Potential Areas of Ambiguity.","authors":"Yuxin Niu, Jiayue Xie, Zhiyong Li","doi":"10.1016/j.jtho.2024.08.035","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.08.035","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 12","pages":"e100-e101"},"PeriodicalIF":21.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792054","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":"RELAY: Final Overall Survival for Erlotinib Plus Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC.","authors":"Kazuhiko Nakagawa, Edward B Garon, Takashi Seto, Makoto Nishio, Santiago Ponce Aix, Luis Paz-Ares, Chao-Hua Chiu, Keunchil Park, Silvia Novello, Ernest Nadal, Kazumi Nishino, Kiyotaka Yoh, Jin-Yuan Shih, Jeannie Y K Chik, Denis Moro-Sibilot, Tarun Puri, Sunoj Chacko Varughese, Bente Frimodt-Moller, Carla Visseren-Grul, Martin Reck","doi":"10.1016/j.jtho.2024.11.032","DOIUrl":"10.1016/j.jtho.2024.11.032","url":null,"abstract":"<p><strong>Introduction: </strong>RELAY, a global double-blind, placebo-controlled phase 3 study (NCT02411448) found statistically significant improvement in progression-free survival (primary end point) for ramucirumab (RAM) plus erlotinib (ERL) (RAM + ERL) in patients with untreated EGFR-mutated metastatic NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46-0.76, p < 0.0001; median progression-free survival: 19.4 versus 12.4 mo). Here, we report the final overall survival (OS; secondary end point) outcomes for the intention-to-treat population.</p><p><strong>Methods: </strong>Between January 2016 and February 2018, 449 eligible patients with an EGFR exon 19del or L858R mutation and no central nervous system metastases were randomized (1:1) to ERL (150 mg/day) with RAM (10 mg/kg every two weeks, N = 224) or placebo (N = 225).</p><p><strong>Results: </strong>At data cutoff, 297 deaths were reported (overall event rate = 66%), with a median follow-up of 45.1 months (interquartile range: 26.7-71.2), an OS HR of 0.98 (95% CI: 0.78-1.24, p = 0.864), and median OS of 51.1 months (RAM + ERL) and 46.0 months (placebo + ERL). Outcomes in subsets of patients with poor prognosis (L858R or TP53 co-mutation) suggest a directional improvement in OS (L858R: HR = 0.87, 95% CI: 0.62-1.22; exon 19del: HR = 1.13, 95% CI: 0.83-1.55; TP53 co-mutation: HR = 0.83, 95% CI: 0.58-1.19; TP53-wild-type: HR = 1.22, 95% CI: 0.87-1.72). Treatment-emergent T790M rates were similar between arms. Over 80% of patients received post-study discontinuation therapy (>50% received osimertinib in comparable numbers between arms). The safety profile for RAM + ERL was consistent with previous reports with no increased toxicity over time or new safety signals observed.</p><p><strong>Conclusion: </strong>In RELAY, OS was not significantly improved with similar long OS durations in both treatment arms.</p><p><strong>Clinical trial information: </strong>ClinicalTrials.gov Identifier: NCT02411448.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770176","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":"Receptor Tyrosine Kinase Fusion-Mediated Resistance to EGFR TKI in EGFR-Mutant NSCLC: A Multi-Center Analysis and Literature Review.","authors":"Yang Xia, Kaiwen Wang, Jing Zhao, Zhaohui Arter, Yongchang Zhang, Jiaqi Zhou, Yuefei Lu, Liang Zeng, Robyn Du, Jennifer A Owens, Yasir Y Elamin, Carl M Gay, Ferdinandos Skoulidis, Anne S Tsao, Charles Lu, Tina Cascone, Don L Gibbons, Jianjun Zhang, Olivia Chen, Kevin K S Mok, Misako Nagasaka, Wen Li, John V Heymach, Sai-Hong Ignatius Ou, Molly Li, Xiuning Le","doi":"10.1016/j.jtho.2024.11.027","DOIUrl":"10.1016/j.jtho.2024.11.027","url":null,"abstract":"<p><strong>Introduction: </strong>Drug resistance remains a major clinical challenge in EGFR-mutant NSCLC tumors owing to pathway reactivation, pathway bypass, and pathway indifference resistance mechanisms to evade tyrosine kinase inhibitor (TKI) suppression. Fusion of receptor tyrosine kinases (RTKs), such as RET, ALK, and FGFR3, has been reported to mediate EGFR TKI resistance. Given the rarity of these fusions and the heterogeneous nature of the condition, no prospective clinical trials evaluated the incidence, safety, and therapeutic benefit of dual EGFR-RTK inhibition.</p><p><strong>Methods: </strong>We queried clinical databases from multiple institutions to identify patients who had RTK fusions detected on next-generation sequencing testing results from tissue or blood at five institutions: the Second Affiliated Hospital Zhejiang University School of Medicine, Hunan Cancer Hospital, Prince of Wales Hospital Chinese University of Hong Kong, Chao Family Cancer Center, and the University of Texas MD Anderson Cancer Center from March 1, 2016, to September 30, 2023. The data analyzed included objective response rate (ORR) to treatment post RTK fusion detection, duration of treatment, and safety. A comprehensive literature search was conducted to identify patients with RTK fusion as the primary resistance mechanism in EGFR-mutated NSCLC patients.</p><p><strong>Results: </strong>Twenty-seven patients were identified to be eligible in the analysis. ALK fusions were most reported (42.9%), followed by RET fusions (35.7%). Fifteen patients received dual TKI after fusion detection and nine received fusion targeting single TKIs. The median time on treatment was 169 days or 5.8 months (35-1050 d). ORR by the Response Evaluation Criteria in Solid Tumors in the evaluable 25 patients was 24% and the disease control rate was 80%. In 14 evaluable patients who received dual TKI therapy, ORR by the Response Evaluation Criteria in Solid Tumors was 21.4%, and the disease control rate was 78.6%. No new toxicities were observed with dual EGFR-RTK inhibition. In the literature review, after pooling 291 patients from 59 studies, RET fusions were the most common (50.0%), followed by BRAF (13.3%), ALK (13.3%), FGFR (10%), NTRK (5.3%), EGFR (1.7%), ROS1 (1.3%), MET (1%), and ERBB (0.7%).</p><p><strong>Conclusion: </strong>The emergence of RTK fusions is one of the mechanisms of bypass resistance of EGFR TKI. Dual inhibition of EGFR-RTK was safe and efficacious in patients with targetable RTK fusion after progression to EGFR TKIs.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770102","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":"Sex and Common Germline Variants Affect the Toxicity Profile and Pharmacokinetics of Alectinib: A Nationwide Cohort Study in Patients With ALK-Positive NSCLC.","authors":"Niels Heersche, Daan A C Lanser, M Benthe Muntinghe-Wagenaar, Ma Ida Mohmaed Ali, Ezgi B Ulas, Tessa M A Trooster, Evert de Jonge, Esther Oomen-de Hoop, Marthe S Paats, Idris Bahce, Sander Croes, Lizza E L Hendriks, Anthonie J van der Wekken, Anne-Marie C Dingemans, Alwin D R Huitema, Ron H N van Schaik, Ron H J Mathijssen, G D Marijn Veerman","doi":"10.1016/j.jtho.2024.11.025","DOIUrl":"10.1016/j.jtho.2024.11.025","url":null,"abstract":"<p><strong>Introduction: </strong>Alectinib, a small-molecule kinase inhibitor, is used as first-line treatment for ALK-positive (ALK+) NSCLC. Albeit generally well-tolerated, a considerable subset of patients requires dose adjustments due to drug-related toxicity. Single-nucleotide polymorphisms in genes related to the metabolism of alectinib may upfront identify patients at risk for toxicity.</p><p><strong>Methods: </strong>In this multicenter observational cohort study in patients with advanced ALK+ NSCLC receiving alectinib treatment, we investigated the association between toxicity, pharmacokinetics, and key genetic variants in ABCB1, CYP3A4, PPAR-α, POR, and CYP3A5. Data on demographics, adverse events, and alectinib trough levels were collected from five hospitals.</p><p><strong>Results: </strong>Among 215 patients, 47% experienced severe toxicity. Women experienced more severe toxicity (female versus male: 56% versus 34%; p = 0.001) and had +35% higher alectinib trough levels (p < 0.001). Homozygous carriers of the PPAR-α 209G>A variant exhibited a higher incidence of grade greater than or equal to 3 toxicity (38%) compared with patients who carried at least one wild-type allele (11%) (p = 0.004). This remained significant after Bonferroni correction. Patients who experienced severe toxicity had +18.5% (95% confidence interval: 2.9%-36.6%; p = 0.019) higher trough levels.</p><p><strong>Conclusions: </strong>Female patients encounter more severe toxicity due to higher alectinib exposure, which warrants further exploration. PPAR-α 209G>A significantly increased relevant alectinib-induced toxicity, most likely due to an increase in alectinib exposure. Pretreatment testing for genetic variants with a subsequent dose reduction could provide a viable approach to reduce alectinib-related toxicity.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770182","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":"FGTI-2734 Inhibits ERK Reactivation to Overcome Sotorasib Resistance in KRAS G12C Lung Cancer.","authors":"Aslamuzzaman Kazi, Hitesh Kumar Kantilal Vasiyani, Deblina Ghosh, Dipankar Bandyopadhyay, Rachit D Shah, Vignesh Vudatha, Jose Trevino, Said M Sebti","doi":"10.1016/j.jtho.2024.11.022","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.11.022","url":null,"abstract":"<p><p>KRAS G12C targeted therapies, such as sotorasib, represent a major breakthrough, but overall response rates and progression-free survival for patients with KRAS G12C lung cancer are modest due to the emergence of resistance mechanisms involving adaptive reactivation of ERK, which requires wild-type (WT) HRAS and NRAS membrane localization. Here, we demonstrate that the dual farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT-1) inhibitor FGTI-2734 inhibits WT RAS membrane localization and sotorasib-induced ERK feedback reactivation, and overcomes sotorasib adaptive resistance. The combination of FGTI-2734 and sotorasib is synergistic at inhibiting the viability and inducing apoptosis of KRAS G12C lung cancer cells, including those highly resistant to sotorasib. FGTI-2734 enhances sotorasib's anti-tumor activity in vivo leading to significant tumor regression of a patient-derived xenograft (PDX) from a patient with KRAS G12C lung cancer as well as several xenografts from highly sotorasib-resistant KRAS G12C human lung cancer cells. Importantly, treatment of mice with FGTI-2734 inhibited sotorasib-induced ERK reactivation in KRAS G12C PDX, and treatment of mice with the combination of FGTI-2734 and sotorasib were also significantly more effective at suppressing in vivo the levels of P-ERK in sotorasib-resistant human KRAS G12C lung cancer xenografts as well as a PDX. Our findings provide a foundation for overcoming sotorasib resistance and potentially improving the treatment outcomes of KRAS G12C lung cancer.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739924","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":"Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report.","authors":"Batel Blechter, Chao Agnes Hsiung, Xiaoyu Wang, Haoyu Zhang, Wei Jie Seow, Jianxin Shi, Nilanjan Chatterjee, Hee Nam Kim, Maria Pik Wong, Yun-Chul Hong, Jason Y Y Wong, Juncheng Dai, H Dean Hosgood, Zhaoming Wang, I-Shou Chang, Jiyeon Choi, Jiucun Wang, Minsun Song, Wei Hu, Wei Zheng, Jin Hee Kim, Baosen Zhou, Demetrius Albanes, Min-Ho Shin, Lap Ping Chung, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young Tae Kim, Xiao-Ou Shu, Young-Chul Kim, Roel C H Vermeulen, Bryan A Bassig, Jiang Chang, James Chung Man Ho, Bu-Tian Ji, Michiaki Kubo, Yataro Daigo, Yukihide Momozawa, Yoichiro Kamatani, Takayuki Honda, Hideo Kunitoh, Shun-Ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Masahiro Tsuboi, Koichi Goto, Zhihua Yin, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Kimihiro Shimizu, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Wu-Chou Su, Yuh-Min Chen, Gee-Chen Chang, Kuan-Yu Chen, Ming-Shyan Huang, Hsien-Chih Lin, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Chien-Jen Chen, Yu-Tang Gao, Chen Wu, Biyun Qian, Daru Lu, Jianjun Liu, Hyo-Sung Jeon, Chin-Fu Hsiao, Jae Sook Sung, Ying-Huang Tsai, Yoo Jin Jung, Huan Guo, Zhibin Hu, Tzu-Yu Chen, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Sonja I Berndt, Wei Wu, Junwen Wang, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Chung-Hsing Chen, Jun Xu, Peng Guan, Wen Tan, Chih-Liang Wang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, Qiuyin Cai, In Kyu Park, Ping Xu, Qincheng He, Chih-Yi Chen, Junjie Wu, Wei-Yen Lim, Kun-Chieh Chen, John K C Chan, Jihua Li, Hongyan Chen, Chong-Jen Yu, Li Jin, Joseph F Fraumeni, Jie Liu, Maria Teresa Landi, Taiki Yamaji, Yang Yang, Belynda Hicks, Kathleen Wyatt, Shengchao A Li, Hongxia Ma, Bao Song, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Li-Hsin Chien, Fang-Yu Tsai, Jinming Yu, Victoria L Stevens, Pan-Chyr Yang, Dongxin Lin, Kexin Chen, Yi-Long Wu, Keitaro Matsuo, Nathaniel Rothman, Kouya Shiraishi, Hongbing Shen, Stephen J Chanock, Takashi Kohno, Qing Lan","doi":"10.1016/j.jtho.2024.11.019","DOIUrl":"10.1016/j.jtho.2024.11.019","url":null,"abstract":"<p><p>We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the EGFR gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared with EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (odds ratio = 8.63, 95% confidence interval: 5.67-13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (odds ratio = 3.50, 95% confidence interval: 2.44-5.00) (p-heterogeneity = 3.66 × 10^-3). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710577","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}