{"title":"Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.","authors":"Hwayoung Noh, Jeeyoo Lee, Nazlisadat Seyed Khoei, Laia Peruchet-Noray, Daehee Kang, Beatrice Fervers, Karl-Heinz Wagner, Aesun Shin, Heinz Freisling","doi":"10.1038/s41416-024-02847-9","DOIUrl":"10.1038/s41416-024-02847-9","url":null,"abstract":"<p><strong>Background: </strong>Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent.</p><p><strong>Methods: </strong>In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression.</p><p><strong>Results: </strong>During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar.</p><p><strong>Conclusions: </strong>Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388222","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}
Nadia Øgaard, Sarah Østrup Jensen, Mai-Britt Worm Ørntoft, Christina Demuth, Mads Heilskov Rasmussen, Tenna Vesterman Henriksen, Jesper Nors, Amanda Frydendahl, Iben Lyskjær, Marijana Nesic, Christina Therkildsen, Jakob Kleif, Mikail Gögenur, Lars Nannestad Jørgensen, Jesper Vilandt, Jakob Benedict Seidelin, Kåre Anderson Gotschalck, Claudia Jaensch, Berit Andersen, Uffe Schou Løve, Ole Thorlacius-Ussing, Per Vadgaard Andersen, Thomas Kolbro, Alessio Monti, Jeppe Kildsig, Peter Bondeven, Nis Hallundbæk Schlesinger, Lene Hjerrild Iversen, Morten Rasmussen, Ismail Gögenur, Jesper Bertram Bramsen, Claus Lindbjerg Andersen
{"title":"Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer.","authors":"Nadia Øgaard, Sarah Østrup Jensen, Mai-Britt Worm Ørntoft, Christina Demuth, Mads Heilskov Rasmussen, Tenna Vesterman Henriksen, Jesper Nors, Amanda Frydendahl, Iben Lyskjær, Marijana Nesic, Christina Therkildsen, Jakob Kleif, Mikail Gögenur, Lars Nannestad Jørgensen, Jesper Vilandt, Jakob Benedict Seidelin, Kåre Anderson Gotschalck, Claudia Jaensch, Berit Andersen, Uffe Schou Løve, Ole Thorlacius-Ussing, Per Vadgaard Andersen, Thomas Kolbro, Alessio Monti, Jeppe Kildsig, Peter Bondeven, Nis Hallundbæk Schlesinger, Lene Hjerrild Iversen, Morten Rasmussen, Ismail Gögenur, Jesper Bertram Bramsen, Claus Lindbjerg Andersen","doi":"10.1038/s41416-024-02867-5","DOIUrl":"10.1038/s41416-024-02867-5","url":null,"abstract":"<p><strong>Background: </strong>Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup.</p><p><strong>Methods: </strong>ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722).</p><p><strong>Results: </strong>After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6).</p><p><strong>Conclusions: </strong>Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399371","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}
Giulia Miglietta, Marco Russo, Giovanni Capranico, Jessica Marinello
{"title":"Stimulation of cGAS-STING pathway as a challenge in the treatment of small cell lung cancer: a feasible strategy?","authors":"Giulia Miglietta, Marco Russo, Giovanni Capranico, Jessica Marinello","doi":"10.1038/s41416-024-02821-5","DOIUrl":"10.1038/s41416-024-02821-5","url":null,"abstract":"<p><p>Lung cancer has a significant incidence among the population and, unfortunately, has an unfavourable prognosis in most cases. The World Health Organization (WHO) classifies lung tumours into two subtypes based on their phenotype: the Non-Small Cell Lung Cancer (NSCLC) and the Small Cell Lung Cancer (SCLC). SCLC treatment, despite advances in chemotherapy and radiotherapy, is often unsuccessful for cancer recurrence highlighting the need to develop novel therapeutic strategies. In this review, we describe the genetic landscape and tumour microenvironment that characterize the pathological processes of SCLC and how they are responsible for tumour immune evasion. The immunosuppressive mechanisms engaged in SCLC are critical factors to understand the failure of immunotherapy in SCLC and, conversely, suggest that new signalling pathways, such as cGAS/STING, should be investigated as possible targets to stimulate an innate immune response in this subtype of lung cancer. The full comprehension of the innate immunity of cancer cells is thus crucial to open new challenges for successful immunotherapy in treating SCLC and improving patient outcomes.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104505","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}
Razia Rahman, Muhammed H Rahaman, Adrienne R Hanson, Nicholas Choo, Jianling Xie, Scott L Townley, Raj Shrestha, Ramin Hassankhani, Saiful Islam, Susanne Ramm, Kaylene J Simpson, Gail P Risbridger, Giles Best, Margaret M Centenera, Steven P Balk, Ganessan Kichenadasse, Renea A Taylor, Lisa M Butler, Wayne D Tilley, Simon J Conn, Mitchell G Lawrence, Shudong Wang, Luke A Selth
{"title":"Author Correction: CDK9 inhibition constrains multiple oncogenic transcriptional and epigenetic pathways in prostate cancer.","authors":"Razia Rahman, Muhammed H Rahaman, Adrienne R Hanson, Nicholas Choo, Jianling Xie, Scott L Townley, Raj Shrestha, Ramin Hassankhani, Saiful Islam, Susanne Ramm, Kaylene J Simpson, Gail P Risbridger, Giles Best, Margaret M Centenera, Steven P Balk, Ganessan Kichenadasse, Renea A Taylor, Lisa M Butler, Wayne D Tilley, Simon J Conn, Mitchell G Lawrence, Shudong Wang, Luke A Selth","doi":"10.1038/s41416-024-02862-w","DOIUrl":"10.1038/s41416-024-02862-w","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495472","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":"Whole tumour- and subregion-based radiomics of contrast-enhanced mammography in differentiating HER2 expression status of invasive breast cancers: A double-centre pilot study.","authors":"Simin Wang, Ting Wang, Sailing Guo, Shuangshuang Zhu, Ruchuan Chen, Jinlong Zheng, Tingting Jiang, Ruimin Li, Jinhui Li, Jiawei Li, Xigang Shen, Min Qian, Meng Yang, Shengnan Yu, Chao You, Yajia Gu","doi":"10.1038/s41416-024-02871-9","DOIUrl":"10.1038/s41416-024-02871-9","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the value of whole tumour- and subregion-based radiomics of contrast-enhanced mammography (CEM) in differentiating the HER2 expression status of breast cancers.</p><p><strong>Methods: </strong>352 patients underwent preoperative CEM from two centres were consecutively enroled and divided into the training, internal validation, and external validation cohorts. The lesions were divided into HER2-positive and HER2-negative groups. Besides the radiological features, radiomics features capturing the whole tumour-based (wITH) and subregion-based intratumoral heterogeneity (sITH) were extracted from the craniocaudal view of CEM recombined images. The XGBoost classifier was applied to develop the radiological, sITH, and wITH models. A combined model was constructed by fusing the prediction results of the three models.</p><p><strong>Results: </strong>The mean age of the patients was 51.1 ± 10.7 years. Two radiological features, four wITH features, and three sITH features were selected to establish the models. The combined model significantly improved the AUC to 0.80 ± 0.03 (95% CI: 0.73-0.86), 0.79 ± 0.06 (95% CI: 0.67-0.90), and 0.79 ± 0.05 (95% CI: 0.69-0.89) in the training, internal validation, and external validation cohorts, respectively (All P < 0.05). The combined model showed good agreement between the predicted and observed probabilities and favourable net clinical benefit in the validation cohorts.</p><p><strong>Conclusions: </strong>Both whole tumour- and subregion-based ITH radiomics features of CEM exhibited potential for differentiating the HER2 expression status. Combining conventional radiological features and ITH features can improve the model's performance.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388223","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}
Xingyang Liu, Qinjie Min, Xinxin Cheng, Weimin Zhang, Qingnan Wu, Xu Chen, Mengzhu Lv, Siqi Liu, Huihui Zhao, Di Yang, Yidi Tai, Xiao Lei, Yan Wang, Qimin Zhan
{"title":"Quiescent cancer cells induced by high-density cultivation reveals cholesterol-mediated survival and lung metastatic traits.","authors":"Xingyang Liu, Qinjie Min, Xinxin Cheng, Weimin Zhang, Qingnan Wu, Xu Chen, Mengzhu Lv, Siqi Liu, Huihui Zhao, Di Yang, Yidi Tai, Xiao Lei, Yan Wang, Qimin Zhan","doi":"10.1038/s41416-024-02861-x","DOIUrl":"10.1038/s41416-024-02861-x","url":null,"abstract":"<p><strong>Background: </strong>The metastatic cascade, a multifaceted and highly aggressive process, is the primary cause of mortality. The survival of quiescent cancer cells in circulatory system during metastasis is crucial, yet our comprehension is constrained by the absence of universally accepted quiescent cancer models.</p><p><strong>Method: </strong>We developed a quiescent cancer cell model using high-density cultivation. Based on the scRNA-seq analysis, IP-MS, metabolomics, mouse lung metastasis models, cholesterol assay, PLA and other molecular experiments, we explored the molecular mechanism. Immunofluorescence, atomic force microscope, FluidFM, and shear stress stimulation were used to analyze the cytoskeleton and membrane properties contributing to mechanical force resistance.</p><p><strong>Result: </strong>We established a quiescent cancer cell model induced by high-density cultivation. Single-cell RNA sequencing (scRNA-seq) analysis reveals that CDC25A plays a crucial role in the transition to quiescence, with its expression significantly elevated in the quiescent state. Depletion of CDC25A leads to an increased proliferative capacity, and reduced metastasis under high-density conditions. Mechanistically, upregulated CDC25A in quiescent cells enhances cholesterol metabolism via endosome pathways, leading to cell cycle arrest. This increase in cholesterol reinforces the cytoskeleton, alters membrane properties, and improves resistance to mechanical forces in circulatory system.</p><p><strong>Conclusion: </strong>CDC25A significantly increased the cholesterol metabolism through endosome pathway in quiescent cancer cells, leading to the significant changes in cytoskeleton and membrane properties so as to enhance the resistance of mechanical force in circulatory system, facilitating lung metastasis. In high-density cultivation, quiescent cancer cells, up-regulate cholesterol metabolism by CDC25A through endosome pathway, enhancing the resistance to mechanical force in circulatory system, facilitating lung metastasis.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399372","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":"Correction: Comorbidity in patients with cancer treated at The Christie.","authors":"Azadeh Abravan, Corinne Faivre-Finn, Fabio Gomes, Marcel van Herk, Gareth Price","doi":"10.1038/s41416-024-02884-4","DOIUrl":"10.1038/s41416-024-02884-4","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458460","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}
Michael Pudjihartono, Nicholas Pudjihartono, Justin M O'Sullivan, William Schierding
{"title":"Melanoma-specific mutation hotspots in distal, non-coding, promoter-interacting regions implicate novel candidate driver genes.","authors":"Michael Pudjihartono, Nicholas Pudjihartono, Justin M O'Sullivan, William Schierding","doi":"10.1038/s41416-024-02870-w","DOIUrl":"10.1038/s41416-024-02870-w","url":null,"abstract":"<p><strong>Background: </strong>To develop targeted treatments, it is crucial to identify the full spectrum of genetic drivers in melanoma, including those in non-coding regions. However, recent efforts to explore non-coding regions have primarily focused on gene-adjacent elements such as promoters and non-coding RNAs, leaving intergenic distal regulatory elements largely unexplored.</p><p><strong>Methods: </strong>We used Hi-C chromatin contact data from melanoma cells to map distal, non-coding, promoter-interacting regulatory elements genome-wide in melanoma. Using this \"promoter-interaction network\", alongside whole-genome sequence and gene expression data from the Pan Cancer Analysis of Whole Genomes, we developed multivariate linear regression models to identify distal somatic mutation hotspots that affect promoter activity.</p><p><strong>Results: </strong>We identified eight recurrently mutated hotspots that are novel, melanoma-specific, located in promoter-interacting distal regulatory elements, alter transcription factor binding motifs, and affect the expression of genes (e.g., HSPB7, CLDN1, ADCY9 and FDXR) previously implicated as tumour suppressors/oncogenes in various cancers.</p><p><strong>Conclusions: </strong>Our study suggests additional non-coding drivers beyond the well-characterised TERT promoter in melanoma, offering new insights into the disruption of complex regulatory networks by non-coding mutations that may contribute to melanoma development. Furthermore, our study provides a framework for integrating multiple levels of biological data to uncover cancer-specific non-coding drivers.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375091","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}
Nadin Hawwash, Matthew Sperrin, Glen P Martin, Corinne E Joshu, Roberta Florido, Elizabeth A Platz, Andrew G Renehan
{"title":"Waist circumference-years and cancer risk: a prospective study of the association and comparison of predictive performance with waist circumference and body mass index.","authors":"Nadin Hawwash, Matthew Sperrin, Glen P Martin, Corinne E Joshu, Roberta Florido, Elizabeth A Platz, Andrew G Renehan","doi":"10.1038/s41416-024-02860-y","DOIUrl":"10.1038/s41416-024-02860-y","url":null,"abstract":"<p><strong>Background: </strong>Associations of waist circumferences (WC) and body mass index (BMI) measured once or over time, with cancer incidence were studied. WC is associated with some cancers independent of BMI. Analyses of cumulative central adiposity and cancer are lacking. We investigated associations between waist circumference-years, incorporating exposure time to WC ≥ 102 cm in men or ≥88 cm in women, and cancer, and compared this with single WC or BMI.</p><p><strong>Methods: </strong>Serial WC measurements taken over 9 years in the prospective Atherosclerosis Risk in Communities Study (ARIC) predicted yearly WC. Cox proportional hazards regression estimated hazard ratios (HRs) of cancer incidence for waist circumference-years, WC or BMI, measured in Visit 4. Harrell's C-statistic quantified metric predictive performances.</p><p><strong>Results: </strong>10,172 participants were followed up from Visit 4 for cancer over a median 13.7 for men and 15.8 years for women. For obesity-related cancers, HRs per standard deviation waist circumference-years were 1.14 (95%CI:1.04,1.25) and 1.19 (95%CI:1.12,1.27), respectively. Differences in metric predictive performances were marginal.</p><p><strong>Discussion: </strong>This is the first study to identify positive associations between waist circumference-years and cancer. Waist circumference-years did not provide additional information on cancer risk beyond that of WC and BMI. BMI is routinely measured in clinic so it may be preferred over WC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375092","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}