British Journal of Cancer最新文献

{"title":"Cardiotoxicity following thoracic radiotherapy for lung cancer.","authors":"Gerard M Walls, Carmen Bergom, Joshua D Mitchell, Stacey L Rentschler, Geoffrey D Hugo, Pamela P Samson, Clifford G Robinson","doi":"10.1038/s41416-024-02888-0","DOIUrl":"10.1038/s41416-024-02888-0","url":null,"abstract":"<p><p>Radiotherapy is the standard of care treatment for unresectable NSCLC, combined with concurrent chemotherapy and adjuvant immunotherapy. Despite technological advances in radiotherapy planning and delivery, the risk of damage to surrounding thoracic tissues remains high. Cardiac problems, including arrhythmia, heart failure and ischaemic events, occur in 20% of patients with lung cancer who undergo radiotherapy. As survival rates improve incrementally for this cohort, minimising the cardiovascular morbidity of RT is increasingly important. Problematically, the reporting of cardiac endpoints has been poor in thoracic radiotherapy clinical trials, and retrospective studies have been limited by the lack of standardisation of nomenclature and endpoints. How baseline cardiovascular profile and cardiac substructure radiation dose distribution impact the risk of cardiotoxicity is incompletely understood. As Thoracic Oncology departments seek to expand the indications for radiotherapy, and as the patient cohort becomes older and more comorbid, there is a pressing need for cardiotoxicity to be comprehensively characterised with sophisticated oncology, physics and cardio-oncology evaluations. This review synthesises the evidence base for cardiotoxicity in conventional radiotherapy, focusing on lung cancer, including current data, unmet clinical needs, and future scientific directions.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590072","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":"Perioperative safety of risk-reducing mastectomy.","authors":"Samuel Knoedler, Fortunay Diatta, Felix Kasparbauer, Leonard Knoedler, Bong-Sung Kim, Bohdan Pomahac, Martin Kauke-Navarro","doi":"10.1038/s41416-024-02897-z","DOIUrl":"10.1038/s41416-024-02897-z","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582143","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":"Low-dose arsenic trioxide inhibits pancreatic stellate cell activation via LOXL3 expression to enhance immunotherapy in pancreatic cancer.","authors":"Yue Zhao, Yunlong Li, Jinmao Zou, Tairan Guo, Ziyi Zhong, Yaqing Li, Shaojie Chen, Jiajia Li, Kaihong Huang, Guoda Lian, Yuzhou Huang","doi":"10.1038/s41416-024-02880-8","DOIUrl":"https://doi.org/10.1038/s41416-024-02880-8","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer (PC) is characterized by abnormally fibrotic mesenchyme, which notably influences on the effectiveness of immunotherapy. Low-dose arsenic trioxide (ATO, 1.0 μM) can inhibit the activation of pancreatic stellate cells (PSCs) and affect fibrosis, which is a potential strategy for enhancing the sensitivity to immunotherapy.</p><p><strong>Methods: </strong>Extracellular matrix (ECM) models were employed to assess the regulatory effects of ATO on ECM and peripheral blood mononuclear cells. Orthotopic C57BL/6J models were utilized to evaluate the influence of ATO on CD8⁺T cell infiltration and immunotherapy in PC. Additionally, nanomaterials loaded with ATO designed to specifically target PSCs (scAbFAP-α-HMSNs-PAA-ATO) were produced to enhance targeting effects of ATO.</p><p><strong>Results: </strong>Low-dose ATO (1.0 μM) suppressed PSCs activation, exhibiting potential for synergistic immunotherapy. Under low-dose ATO intervention, ECM underwent remodeling, leading to increases in CD8⁺T cell infiltration, thereby enhancing anti-PD-L1 therapy effect. We further demonstrated that low-dose ATO remodeled ECM by regulating the expression of LOXL3 in PSCs. scAbFAP-α-HMSNs-PAA-ATO exhibited improved targeting capabilities, and enhanced capacity to inhibit fibrosis and sensitize immunotherapy.</p><p><strong>Conclusions: </strong>Our research reveals that low-dose ATO, by regulating LOXL3, remodels the ECM and enhances CD8⁺T cell infiltration, thus sensitizing the efficacy of immunotherapy, which provides a novel strategy for comprehensive treatment to PC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582140","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":"Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study.","authors":"Helga H Hektoen, Kaitlyn M Tsuruda, Lars Fjellbirkeland, Yngvar Nilssen, Odd Terje Brustugun, Bettina K Andreassen","doi":"10.1038/s41416-024-02895-1","DOIUrl":"https://doi.org/10.1038/s41416-024-02895-1","url":null,"abstract":"<p><strong>Background: </strong>Based on favourable results from clinical trials, immune checkpoint inhibitors (ICI) have become the standard first line (1 L) systemic anticancer treatment (SACT) for advanced stage non-small cell lung cancer (NSCLC) without targetable mutations. We evaluate whether these results are generalizable to everyday clinical practice and compare overall survival (OS) of patients treated with ICI to a historical cohort of patients treated with chemotherapy and results from clinical trials.</p><p><strong>Methods: </strong>Our study comprised all advanced NSCLC patients initiating SACT in 2012-21 in Norway. Clinical characteristics and treatment information was retrieved from Norwegian Health Registries.</p><p><strong>Results: </strong>Survival for all 8416 advanced NSCLC patients treated with SACT increased concurrently with the gradual implementation of ICIs. Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients treated with chemotherapy before 2017 (8.0 months). Although median OS for patients treated with pembrolizumab was lower in clinical practice than clinical trials (Keynote-024/189: 26.3/22.0 months), the survival benefit relative to chemotherapy was similar.</p><p><strong>Conclusion: </strong>Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials and confirms the effectiveness of pembrolizumab in routine clinical practice.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567347","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":"Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: a systematic review.","authors":"Bishma Jayathilaka, Farah Mian, Fanny Franchini, George Au-Yeung, Maarten IJzerman","doi":"10.1038/s41416-024-02887-1","DOIUrl":"https://doi.org/10.1038/s41416-024-02887-1","url":null,"abstract":"<p><strong>Background: </strong>Immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) are a treatment-limiting barrier. There are few large-scale studies that estimate irAE prevalence. This paper presents a systematic review that reports the prevalence of irAE by cancer type and ICI.</p><p><strong>Methods: </strong>A systematic review was undertaken in MEDLINE OVID, EMBASE and Web of Science databases from 2017-2021. A total of 293 studies were identified for analysis and, of these, event rate was calculated for 272 studies, which involved 58,291 patients with irAE among 305,879 total patients on ICI. Event rate was calculated by irAE and ICI type.</p><p><strong>Results: </strong>Mean event rate for general irAE occurrence across any grade was 40.0% (37.3-42.7%) and high grade was 19.7% (15.8-23.7%). Mean event rates for six specific types of irAE are reported. Mean event rate for ICI monotherapy was 29.7% (27.7-33.2%), 45.7% (29.6-61.7%) for ICI combination therapy, and 30.3% (27.3-35.0%) for both ICI monotherapy and combination therapy.</p><p><strong>Conclusion: </strong>This systematic review characterises irAE prevalence across current research that examines irAE risk factors across cancers and ICI. The findings confirms that irAE occurrence is very common in the real-world setting, both high grade and irAE across any grade.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567344","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":"Temporal dynamics of immune cell patterns in bladder cancer patients receiving Bacillus Calmette-Guérin therapy.","authors":"Jiang-Li Lu, Yun-Lin Ye, Dan-Dan Zheng, Xin-Yu Shi, Li-Ling Hu, Xiao-Yi Yuan, Tao-Nong Cai, Kun Meng, Neng-Qiao Wen, Yu-Ying Li, Ding-Kang Wang, Fu-Jin Shi, Dan-Ya Liu, Qing-Yu He, Zi-Ke Qin, Chris Zhiyi Zhang, Yun Cao","doi":"10.1038/s41416-024-02883-5","DOIUrl":"https://doi.org/10.1038/s41416-024-02883-5","url":null,"abstract":"<p><strong>Background: </strong>Bacillus Calmette-Guérin (BCG) is capable of enhancing the infiltration of immune cells into the tumour. However the temporal dynamics of immune cell patterns in patients receiving BCG instillation remains unclear.</p><p><strong>Methods: </strong>Ninety-six patients who underwent intravesical BCG therapy, comprising 46 responders and 50 non-responders, were retrospectively enroled to explore the evolving immune landscape. This study involved a detailed examination of sequential samples collected before, during, and after BCG treatment to assess BCG's influence on the immune microenvironment, employing techniques such as immunohistochemistry, fluorescent multiplex immunohistochemistry, and mass spectrometry techniques.</p><p><strong>Results: </strong>Our study found that initial BCG instillation leads to enhanced immune cell infiltration, correlating with treatment efficacy, with responders exhibiting more pronounced increases. Non-responders experience a rise in immune cell infiltration and PD-L1 expression during the first instillation, which returns to baseline after treatment. In non-responders, BCG re-challenge fail to further increase immune cell infiltration into the tumour or improve patient outcomes. Strikingly, proteomics data revealed that GBP1 expression was induced by BCG treatment in non-responders.</p><p><strong>Conclusions: </strong>Our findings demonstrated the induction of tumour PD-L1 expression by BCG in non-responders, and therefore provide insights for the combination of BCG and anti-PD1/anti-PD-L1 therapy.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557220","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":"Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma.","authors":"Matteo Villa, Geeta G Sharma, Federica Malighetti, Mario Mauri, Giulia Arosio, Nicoletta Cordani, Cosimo Lobello, Hugo Larose, Alessandra Pirola, Deborah D'Aliberti, Luca Massimino, Lucrezia Criscuolo, Lisa Pagani, Clizia Chinello, Cristina Mastini, Diletta Fontana, Silvia Bombelli, Raffaella Meneveri, Federica Lovisa, Lara Mussolin, Andrea Janikova, Šárka Pospíšilová, Suzanne D Turner, Giorgio Inghirami, Fulvio Magni, Mario Urso, Fabio Pagni, Daniele Ramazzotti, Rocco Piazza, Roberto Chiarle, Carlo Gambacorti-Passerini, Luca Mologni","doi":"10.1038/s41416-024-02881-7","DOIUrl":"https://doi.org/10.1038/s41416-024-02881-7","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic Large Cell Lymphoma (ALCL) is a rare and aggressive T-cell lymphoma, classified into ALK-positive and ALK-negative subtypes, based on the presence of chromosomal translocations involving the ALK gene. The current standard of treatment for ALCL is polychemotherapy, with a high overall survival rate. However, a subset of patients does not respond to or develops resistance to these therapies, posing a serious challenge for clinicians. Recent targeted treatments such as ALK kinase inhibitors and anti-CD30 antibody-drug conjugates have shown promise but, for a fraction of patients, the prognosis is still unsatisfactory.</p><p><strong>Methods: </strong>We investigated the genetic landscape of ALK + ALCL by whole-exome sequencing; recurring mutations were characterized in vitro and in vivo using transduced ALCL cellular models.</p><p><strong>Results: </strong>Recurrent mutations in FAT family genes and the transcription factor RUNX1T1 were found. These mutations induced changes in ALCL cells morphology, growth, and migration, shedding light on potential factors contributing to treatment resistance. In particular, FAT4 silencing in ALCL cells activated the β-catenin and YAP1 pathways, which play crucial roles in tumor growth, and conferred resistance to chemotherapy. Furthermore, STAT1 and STAT3 were hyper-activated in these cells. Gene expression profiling showed global changes in pathways related to cell adhesion, cytoskeletal organization, and oncogenic signaling. Notably, FAT mutations associated with poor outcome in patients.</p><p><strong>Conclusions: </strong>These findings provide novel insights into the molecular portrait of ALCL, that could help improve treatment strategies and the prognosis for ALCL patients.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543816","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":"The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project.","authors":"Elaine Y L Leung, Helen L Robbins, Shafquat Zaman, Neeraj Lal, Dion Morton, Lisa Dew, Anthony P Williams, Yvonne Wallis, Jennie Bell, Manoj Raghavan, Gary Middleton, Andrew D Beggs","doi":"10.1038/s41416-024-02890-6","DOIUrl":"https://doi.org/10.1038/s41416-024-02890-6","url":null,"abstract":"<p><strong>Background: </strong>The 100,000 Genomes Project established infrastructure for Whole Genome Sequencing (WGS) in the United Kingdom.</p><p><strong>Methods: </strong>A retrospective study of cancer patients recruited to the 100,000 Genomes Project by the West Midlands Genomics Medicine Centre, evaluating clinical relevance of results.</p><p><strong>Results: </strong>After excluding samples with no sequencing data (1678/4851; 34.6%), 3166 sample sets (germline and somatic) from 3067 participants were sequenced. Results of 1256 participants (41.0%) were interpreted (excluding participants who died (308/3067; 10.0%) or were clinically excluded (1503/3067; 49.0%)). Of these, 323 (25.7%) had no variants in genes which may alter management (Domain 1 genes). Of the remaining 933 participants, 552 (59.2%) had clinical recommendations made (718 recommendations in total). These included therapeutic recommendations (377/933; 40.4%), such as clinical trial, unlicensed or licensed therapies or high TMB recommendations, and germline variants warranting clinical genetics review (85/933; 9.1%). At the last follow up, 20.2% of all recommendations were followed (145/718). However, only a small proportion of therapeutic recommendations were followed (5.1%, 25/491).</p><p><strong>Conclusions: </strong>The 100,000 Genomes Project has established infrastructure and regional experience to support personalised cancer care. The majority of those with successful sequencing had actionable variants. Ensuring GTAB recommendations are followed will maximise benefits for patients.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543817","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":"Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer.","authors":"Yuhya Hirahara, Kanako Shimizu, Satoru Yamasaki, Tomonori Iyoda, Shogo Ueda, Shinya Sato, Jotaro Harada, Haruya Saji, Satoshi Fujii, Yohei Miyagi, Etsuko Miyagi, Shin-Ichiro Fujii","doi":"10.1038/s41416-024-02877-3","DOIUrl":"https://doi.org/10.1038/s41416-024-02877-3","url":null,"abstract":"<p><strong>Background: </strong>The immunostimulatory actions of innate and adaptive immune responses play a crucial role in the cancer-immunity cycle. Although cervical cancer (CC) exhibits a high recurrence rate, the relation with lymphocytes in the tumor tissue have not been analyzed.</p><p><strong>Methods: </strong>We analyzed NKT, NK, and T cells, not only in peripheral blood (PB), but also tumor tissue through histological analysis from 23 patients with CC collected before treatment. A correlation of them between PB and the tumor tissue were assessed.</p><p><strong>Results: </strong>We detected functional NKT and NKG2D^hi NK cells and effector CD4⁺ Tregs in PB. In the tumor, we detected the infiltration of LAG-3⁺ TIM-3⁺ CD4⁺ and CD8⁺ T cells rather than NK cells particularly in the invasion front (IF) by fluorescent multiplex immunohistochemistry. The heatmap and correlation analysis revealed that LAG-3⁺ TIM-3⁺ CD8⁺ T cells are highly associated with CD69⁺ CD103^- exhausted CD8⁺ T cells. We identified the statistical relationship between CD4⁺Tregs in PB and the number of LAG-3⁺ TIM-3⁺ CD4⁺ T cells in the IF, which may be related to recurrence in patients with CC.</p><p><strong>Conclusions: </strong>LAG-3⁺ TIM-3⁺ T cells located in the IF may play a key role in regulation of the tumor immune microenvironment.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543815","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":"A proteome-wide association study identifies putative causal proteins for breast cancer risk.","authors":"Tianying Zhao, Shuai Xu, Jie Ping, Guochong Jia, Yongchao Dou, Jill E Henry, Bing Zhang, Xingyi Guo, Michele L Cote, Qiuyin Cai, Xiao-Ou Shu, Wei Zheng, Jirong Long","doi":"10.1038/s41416-024-02879-1","DOIUrl":"https://doi.org/10.1038/s41416-024-02879-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Genome-wide association studies (GWAS) have identified more than 200 breast cancer risk-associated genetic loci, yet the causal genes and biological mechanisms for most loci remain elusive. Proteins, as final gene products, are pivotal in cellular function. In this study, we conducted a proteome-wide association study (PWAS) to identify proteins in breast tissue related to breast cancer risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We profiled the proteome in fresh frozen breast tissue samples from 120 cancer-free European-ancestry women from the Susan G. Komen Tissue Bank (KTB). Protein expression levels were log2-transformed then normalized via quantile and inverse-rank transformations. GWAS data were also generated for these 120 samples. These data were used to build statistical models to predict protein expression levels via cis-genetic variants using the elastic net method. The prediction models were then applied to the GWAS summary statistics data of 133,384 breast cancer cases and 113,789 controls to assess the associations of genetically predicted protein expression levels with breast cancer risk overall and its subtypes using the S-PrediXcan method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 6388 proteins were detected in the normal breast tissue samples from 120 women with a high detection false discovery rate (FDR) p value &lt; 0.01. Among the 5820 proteins detected in more than 80% of participants, prediction models were successfully built for 2060 proteins with R &gt; 0.1 and P &lt; 0.05. Among these 2060 proteins, five proteins were significantly associated with overall breast cancer risk at an FDR p value &lt; 0.1. Among these five proteins, the corresponding genes for proteins COPG1, DCTN3, and DDX6 were located at least 1 Megabase away from the GWAS-identified breast cancer risk variants. COPG1 was associated with an increased risk of breast cancer with a p value of 8.54 × 10&lt;sup&gt;-4&lt;/sup&gt;. Both DCTN3 and DDX6 were associated with a decreased risk of breast cancer with p values of 1.01 × 10&lt;sup&gt;-3&lt;/sup&gt; and 3.25 × 10&lt;sup&gt;-4&lt;/sup&gt;, respectively. The corresponding genes for the remaining two proteins, LSP1 and DNAJA3, were located in previously GWAS-identified breast cancer risk loci. After adjusting for GWAS-identified risk variants, the association for DNAJA3 was still significant (p value of 9.15 × 10&lt;sup&gt;-5&lt;/sup&gt; and adjusted p value of 1.94 × 10&lt;sup&gt;-4&lt;/sup&gt;). However, the significance for LSP1 became weaker with a p value of 0.62. Stratification analyses by breast cancer subtypes identified three proteins, SMARCC1, LSP1, and NCKAP1L, associated with luminal A, luminal B, and ER-positive breast cancer. NCKAP1L was located at least 1Mb away from the GWAS-identified breast cancer risk variants. After adjusting for GWAS-identified breast cancer risk variants, the association for protein LSP1 was still significant (adjusted p value of 6.43 × 10&lt;sup&gt;-3&lt;/sup&gt; for luminal B subtype).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;We c","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521001","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}