首页 > 最新文献

Journal of the National Cancer Institute最新文献

英文 中文
Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma 与肿瘤免疫异质性相关的放射组学特征可预测局部复发鼻咽癌患者的生存率
Pub Date : 2024-04-19 DOI: 10.1093/jnci/djae081
Da-Feng Lin, Hai-Lin Li, Ting Liu, Xiao-Fei Lv, Chuan-Miao Xie, Xiao-Min Ou, Jian Guan, Ye Zhang, Wen-Bin Yan, Mei-Lin He, Meng-Yuan Mao, Xun Zhao, Lian-Zhen Zhong, Wen-Hui Chen, Qiu-Yan Chen, Hai-Qiang Mai, Rou-Jun Peng, Jie Tian, Lin-Quan Tang, Di Dong
Background The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. Methods This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. Results The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. Conclusions An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.
背景 局部复发性鼻咽癌(lrNPC)传统临床指标的预后价值有限,因为它们无法反映肿瘤内的异质性。我们的目的是开发一种放射组学特征,以揭示肿瘤免疫异质性并预测 lrNPC 的生存期。方法 这项多中心回顾性研究纳入了 921 例 lrNPC 患者。在一个训练队列中开发了基于治疗前磁共振成像特征的机器学习特征和提名图,用于预测总生存期(OS),并在两个独立队列中进行了验证。为进行比较,还构建了临床提名图和综合提名图。通过一致性指数(C-index)和接收者操作特征曲线分析评估了提名图的性能。据此,患者被划分为不同的风险组别。通过 RNA 测序(RNA-seq)分析探讨了特征的生物学特征和免疫浸润。结果 机器学习特征和提名图显示出与临床提名图相当的预后能力,在训练组、内部组和外部验证组中的C指数分别为0.729、0.718和0.731。该特征与临床变量的整合大大提高了预测性能。所提出的特征能有效区分OS率明显不同的风险组别。亚组分析表明,建议对低风险患者进行局部挽救治疗。探索性RNA-seq分析显示,不同风险组的干扰素反应和淋巴细胞浸润存在差异。结论 基于MRI的放射学特征能更准确地预测OS。所提出的与肿瘤免疫异质性相关的特征可作为一种有价值的工具,帮助对lrNPC患者进行预后分层并指导个体化治疗。
{"title":"Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma","authors":"Da-Feng Lin, Hai-Lin Li, Ting Liu, Xiao-Fei Lv, Chuan-Miao Xie, Xiao-Min Ou, Jian Guan, Ye Zhang, Wen-Bin Yan, Mei-Lin He, Meng-Yuan Mao, Xun Zhao, Lian-Zhen Zhong, Wen-Hui Chen, Qiu-Yan Chen, Hai-Qiang Mai, Rou-Jun Peng, Jie Tian, Lin-Quan Tang, Di Dong","doi":"10.1093/jnci/djae081","DOIUrl":"https://doi.org/10.1093/jnci/djae081","url":null,"abstract":"Background The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. Methods This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. Results The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. Conclusions An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"280 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systematic investigation of genetically determined plasma and urinary metabolites to discover potential interventional targets for colorectal cancer 系统调查基因测定的血浆和尿液代谢物,发现结直肠癌的潜在干预靶点
Pub Date : 2024-04-18 DOI: 10.1093/jnci/djae089
Jing Sun, Jianhui Zhao, Siyun Zhou, Xinxuan Li, Tengfei Li, Lijuan Wang, Shuai Yuan, Dong Chen, Philip J Law, Susanna C Larsson, Susan M Farrington, Richard S Houlston, Malcolm G Dunlop, Evropi Theodoratou, Xue Li
Background We aimed to identify plasma and urinary metabolites related to colorectal cancer (CRC) risk and elucidate their mediator role in the associations between modifiable risk factors and CRC. Methods Metabolite quantitative trait loci were derived from two published metabolomics genome-wide association studies (GWASs), and summary-level data were extracted for 651 plasma metabolites and 208 urinary metabolites. Genetic associations with CRC were obtained from a large-scale GWAS meta-analysis (100,204 cases; 154,587 controls) and the FinnGen cohort (4,957 cases; 304,197 controls). Mendelian randomization (MR) and colocalization analyses were performed to evaluate the causal roles of metabolites in CRC. Druggability evaluation was employed to prioritize potential therapeutic targets. Multivariable MR and mediation estimation were conducted to elucidate the mediating effects of metabolites on the associations between modifiable risk factors and CRC. Results The study identified 30 plasma metabolites and four urinary metabolites for CRC. Plasma sphingomyelin and urinary lactose, which were positively associated with CRC risk, could be modulated by drug interventions (ie, Olipudase alfa, Tilactase). Thirteen modifiable risk factors were associated with nine metabolites and eight of these modifiable risk factors were associated with CRC risk. These nine metabolites mediated the effect of modifiable risk factors (Actinobacteria, BMI, waist-hip ratio, fasting insulin, smoking initiation) on CRC. Conclusion This study identified key metabolite biomarkers associated with CRC and elucidated their mediator roles in the associations between modifiable risk factors and CRC. These findings provide new insights into the etiology and potential therapeutic targets for CRC and the etiological pathways of modifiable environmental factors with CRC.
背景 我们旨在确定与结直肠癌(CRC)风险相关的血浆和尿液代谢物,并阐明它们在可改变的风险因素与 CRC 之间的关联中的中介作用。方法 从两项已发表的代谢组学全基因组关联研究(GWAS)中提取代谢物定量性状位点,并提取了 651 种血浆代谢物和 208 种尿液代谢物的摘要级数据。与 CRC 的遗传关联来自大规模 GWAS meta 分析(100,204 例病例;154,587 例对照)和 FinnGen 队列(4,957 例病例;304,197 例对照)。为了评估代谢物在 CRC 中的因果作用,进行了孟德尔随机化(MR)和共定位分析。采用可药用性评估对潜在的治疗靶点进行优先排序。进行了多变量 MR 和中介估计,以阐明代谢物对可改变风险因素与 CRC 之间关联的中介效应。结果 研究发现了 30 种血浆代谢物和 4 种尿液代谢物与 CRC 有关。血浆鞘磷脂和尿液乳糖与 CRC 风险呈正相关,可通过药物干预(即 Olipudase alfa 和 Tilactase)调节。13种可改变的风险因素与9种代谢物相关,其中8种可改变的风险因素与CRC风险相关。这九种代谢物介导了可改变的风险因素(放线菌、体重指数、腰臀比、空腹胰岛素、开始吸烟)对 CRC 的影响。结论 本研究确定了与 CRC 相关的关键代谢物生物标志物,并阐明了它们在可改变的风险因素与 CRC 之间的关联中的中介作用。这些发现为 CRC 的病因学和潜在治疗目标以及可改变的环境因素与 CRC 的病因学途径提供了新的见解。
{"title":"Systematic investigation of genetically determined plasma and urinary metabolites to discover potential interventional targets for colorectal cancer","authors":"Jing Sun, Jianhui Zhao, Siyun Zhou, Xinxuan Li, Tengfei Li, Lijuan Wang, Shuai Yuan, Dong Chen, Philip J Law, Susanna C Larsson, Susan M Farrington, Richard S Houlston, Malcolm G Dunlop, Evropi Theodoratou, Xue Li","doi":"10.1093/jnci/djae089","DOIUrl":"https://doi.org/10.1093/jnci/djae089","url":null,"abstract":"Background We aimed to identify plasma and urinary metabolites related to colorectal cancer (CRC) risk and elucidate their mediator role in the associations between modifiable risk factors and CRC. Methods Metabolite quantitative trait loci were derived from two published metabolomics genome-wide association studies (GWASs), and summary-level data were extracted for 651 plasma metabolites and 208 urinary metabolites. Genetic associations with CRC were obtained from a large-scale GWAS meta-analysis (100,204 cases; 154,587 controls) and the FinnGen cohort (4,957 cases; 304,197 controls). Mendelian randomization (MR) and colocalization analyses were performed to evaluate the causal roles of metabolites in CRC. Druggability evaluation was employed to prioritize potential therapeutic targets. Multivariable MR and mediation estimation were conducted to elucidate the mediating effects of metabolites on the associations between modifiable risk factors and CRC. Results The study identified 30 plasma metabolites and four urinary metabolites for CRC. Plasma sphingomyelin and urinary lactose, which were positively associated with CRC risk, could be modulated by drug interventions (ie, Olipudase alfa, Tilactase). Thirteen modifiable risk factors were associated with nine metabolites and eight of these modifiable risk factors were associated with CRC risk. These nine metabolites mediated the effect of modifiable risk factors (Actinobacteria, BMI, waist-hip ratio, fasting insulin, smoking initiation) on CRC. Conclusion This study identified key metabolite biomarkers associated with CRC and elucidated their mediator roles in the associations between modifiable risk factors and CRC. These findings provide new insights into the etiology and potential therapeutic targets for CRC and the etiological pathways of modifiable environmental factors with CRC.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Measures of physical function clarify the prognostic blur of cancer survivorship. 身体机能的测量可明确癌症幸存者的预后。
Pub Date : 2024-04-17 DOI: 10.1093/jnci/djae076
Justin C Brown
{"title":"Measures of physical function clarify the prognostic blur of cancer survivorship.","authors":"Justin C Brown","doi":"10.1093/jnci/djae076","DOIUrl":"https://doi.org/10.1093/jnci/djae076","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"17 S3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140693001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adolescents and young adults (AYA) with cancer: the clinical course of COVID-19 infections. 青少年癌症患者:COVID-19 感染的临床过程。
Pub Date : 2024-04-16 DOI: 10.1093/jnci/djae085
Julie A Wolfson, Elizabeth S Davis, Aniket Saha, Isaac Martinez, David McCall, Prachi Kothari, Julienne Brackett, David S Dickens, Alissa R. Kahn, Carla Schwalm, Archana Sharma, Joshua Richman, Branko Cuglievan, Smita Bhatia, C. Dai, Jennifer M Levine, Emily E. Johnston
Adolescents and Young Adults (AYAs: 15-39 y) with cancer face unique vulnerabilities, yet remain under-represented on clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8-12%). Thus, we leveraged the Pediatric Oncology COVID-19 Case Report (POCC) to examine the clinical course of COVID-19 among AYAs with cancer. POCC collects de-identified clinical and sociodemographic data regarding 0-39yo with cancer (AYAs = 37%) and COVID-19 from >100 institutions. Between 04/01/2020-11/28/2023, 191 older AYAs [22-39y] and 640 younger AYAs [15-21y] were captured. Older AYAs were less often hospitalized (p < .001), admitted to the intensive care unit (ICU, p = .02), and/or required respiratory support (p = .057). In multivariable analyses, older AYAs faced 80% lower odds of ICU admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of ICU admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform pediatric/adult oncology teams surrounding COVID-19 management and prevention.
患有癌症的青少年和年轻成人(AYAs:15-39 岁)面临着独特的脆弱性,但在临床试验(包括癌症中 COVID-19 的成人登记)中的代表性仍然不足(AYAs:8-12%)。因此,我们利用 "儿科肿瘤 COVID-19 病例报告"(POCC)来研究青少年癌症患者的 COVID-19 临床病程。POCC 从超过 100 家机构收集了 0-39 岁癌症患者(青少年=37%)和 COVID-19 的去标识化临床和社会人口数据。在 2020 年 1 月 4 日至 2023 年 11 月 28 日期间,共采集了 191 名年龄较大的青少年患者 [22-39 岁] 和 640 名年龄较小的青少年患者 [15-21 岁]。老年亚健康者住院(p < .001)、入住重症监护室(ICU,p = .02)和/或需要呼吸支持(p = .057)的情况较少。在多变量分析中,年龄较大的亚健康患者入住重症监护室的几率要低 80%,但改变癌症导向疗法的几率要高 2.3 倍。未接种疫苗的患者入住重症监护室的几率要高出 5.4 倍。在罹患癌症的青壮年患者中,COVID-19 的发病过程因年龄而异。这些发现可为儿科/成人肿瘤团队提供有关 COVID-19 管理和预防的信息。
{"title":"Adolescents and young adults (AYA) with cancer: the clinical course of COVID-19 infections.","authors":"Julie A Wolfson, Elizabeth S Davis, Aniket Saha, Isaac Martinez, David McCall, Prachi Kothari, Julienne Brackett, David S Dickens, Alissa R. Kahn, Carla Schwalm, Archana Sharma, Joshua Richman, Branko Cuglievan, Smita Bhatia, C. Dai, Jennifer M Levine, Emily E. Johnston","doi":"10.1093/jnci/djae085","DOIUrl":"https://doi.org/10.1093/jnci/djae085","url":null,"abstract":"Adolescents and Young Adults (AYAs: 15-39 y) with cancer face unique vulnerabilities, yet remain under-represented on clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8-12%). Thus, we leveraged the Pediatric Oncology COVID-19 Case Report (POCC) to examine the clinical course of COVID-19 among AYAs with cancer. POCC collects de-identified clinical and sociodemographic data regarding 0-39yo with cancer (AYAs = 37%) and COVID-19 from >100 institutions. Between 04/01/2020-11/28/2023, 191 older AYAs [22-39y] and 640 younger AYAs [15-21y] were captured. Older AYAs were less often hospitalized (p < .001), admitted to the intensive care unit (ICU, p = .02), and/or required respiratory support (p = .057). In multivariable analyses, older AYAs faced 80% lower odds of ICU admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of ICU admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform pediatric/adult oncology teams surrounding COVID-19 management and prevention.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"18 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140697339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A population-based study of COVID-19 mortality risk in US cancer patients 基于人群的美国癌症患者 COVID-19 死亡风险研究
Pub Date : 2024-04-13 DOI: 10.1093/jnci/djae086
Kyle A Mani, Xue Wu, Daniel E Spratt, Ming Wang, Nicholas G Zaorsky
Background In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. Methods A total of 4,020,669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database were abstracted. We investigated prognostic factors for death due to COVID-19 using a cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios (SMRs) were calculated using observed mortality counts from SEER and expected mortality based on U.S. mortality rates. Results 291,323 patients died, with 14,821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10,000-persons years, and SMR of COVID-19 was 2.30 (95% CI: 2.26-2.34, p &lt; .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 non-cancer causes of death. Patients who are older (80+ vs &lt; =49 years old: HR 21.47, 95% CI: 19.34-23.83), male (vs female: HR 1.46, 95% CI: 1.40-1.51), unmarried (vs married: HR 1.47, 95% CI: 1.42-1.53), and Hispanic or Non-Hispanic African American (vs Non-Hispanic White: HR 2.04, 95% CI: 1.94-2.14 and HR 2.03, 95% CI: 1.94-2.14, respectively) were at greatest risk of COVID-19 mortality. Conclusions and Relevance We observed that people living with cancer are at two times greater risk of dying from COVID-19 compared to the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.
背景 在本研究中,我们对美国癌症队列进行了迄今为止最大规模的分析,以描述 COVID-19 的死亡特征。方法 摘录了 2020 年美国国家癌症研究所的监测、流行病学和最终结果 (SEER) 数据库中 15 个亚型的 402.0669 万名癌症患者。我们采用cox比例危险模型研究了COVID-19导致死亡的预后因素,并计算了危险比(HRs)。使用 SEER 的观察死亡率计数和基于美国死亡率的预期死亡率计算标准化死亡率比 (SMR)。结果 291,323 名患者死亡,其中 14,821 人(5.1%)的死亡归因于 COVID-19 感染。COVID-19疾病特异性死亡率为11.81/10,000人年,COVID-19的SMR为2.30(95% CI:2.26-2.34,p &p;lt;.0001)。在 26 个非癌症死因中,COVID-19 是仅次于缺血性心脏病(5.2%)的第二大死因。年龄较大(80 岁以上 vs &lt; =49 岁:HR 21.47,95% CI:19.34-23.83)、男性(vs 女性:HR 1.46,95% CI:1.40-1.51)、未婚(vs 已婚:HR 1.47,95% CI:1.42-1.53)、西班牙裔或非西班牙裔非洲裔美国人(vs 非西班牙裔白人:HR 2.04,95% CI:1.42-1.53)的患者的死亡率较高:HR 2.04,95% CI:1.94-2.14;HR 2.03,95% CI:1.94-2.14)的 COVID-19 死亡率风险最高。结论和相关性 我们观察到,与美国普通人群相比,癌症患者死于 COVID-19 的风险高出两倍。医生和公共卫生官员可利用这项研究制定幸存者计划,以降低 COVID-19 的死亡风险。
{"title":"A population-based study of COVID-19 mortality risk in US cancer patients","authors":"Kyle A Mani, Xue Wu, Daniel E Spratt, Ming Wang, Nicholas G Zaorsky","doi":"10.1093/jnci/djae086","DOIUrl":"https://doi.org/10.1093/jnci/djae086","url":null,"abstract":"Background In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. Methods A total of 4,020,669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database were abstracted. We investigated prognostic factors for death due to COVID-19 using a cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios (SMRs) were calculated using observed mortality counts from SEER and expected mortality based on U.S. mortality rates. Results 291,323 patients died, with 14,821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10,000-persons years, and SMR of COVID-19 was 2.30 (95% CI: 2.26-2.34, p &amp;lt; .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 non-cancer causes of death. Patients who are older (80+ vs &amp;lt; =49 years old: HR 21.47, 95% CI: 19.34-23.83), male (vs female: HR 1.46, 95% CI: 1.40-1.51), unmarried (vs married: HR 1.47, 95% CI: 1.42-1.53), and Hispanic or Non-Hispanic African American (vs Non-Hispanic White: HR 2.04, 95% CI: 1.94-2.14 and HR 2.03, 95% CI: 1.94-2.14, respectively) were at greatest risk of COVID-19 mortality. Conclusions and Relevance We observed that people living with cancer are at two times greater risk of dying from COVID-19 compared to the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinic-based interventions for improving access to care: a good start. 改善医疗服务的诊所干预:一个良好的开端。
Pub Date : 2024-04-11 DOI: 10.1093/jnci/djae068
Cathy J. Bradley, K. R. Yabroff, Ya‐Chen Tina Shih
{"title":"Clinic-based interventions for improving access to care: a good start.","authors":"Cathy J. Bradley, K. R. Yabroff, Ya‐Chen Tina Shih","doi":"10.1093/jnci/djae068","DOIUrl":"https://doi.org/10.1093/jnci/djae068","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"21 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140714494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Increasing power in screening trials by testing control-arm specimens: Application to multicancer detection screening 通过检测对照组标本提高筛查试验的能力:应用于多癌检测筛查
Pub Date : 2024-04-11 DOI: 10.1093/jnci/djae083
Hormuzd A Katki, Philip C Prorok, Philip E Castle, Lori M Minasian, Paul F Pinsky
Background Cancer screening trials have required large sample-sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the “Intended Effect” (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control-arm, such as stored blood for multicancer detection (MCD) tests. Methods We simulated hypothetical MCD screening trials to compare power and sample-size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial (NLST), Minnesota Colon Cancer Control Study (MINN-FOBT-A), and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial—colorectal component (PLCO-CRC)). Results Compared to the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality p-values 5-fold (NLST), 33-fold (MINN-FOBT-A), or 14,160-fold (PLCO-CRC), or alternately, reduced sample-size (90% power) by 26% (NLST), 48% (MINN-FOBT-A), or 59% (PLCO-CRC). For potential MCD trial designs requiring 100,000 subjects per-arm to achieve 90% power for multi-cancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37,500-50,000 per arm, depending on assumptions concerning control-arm test-positives. Conclusions Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample-size or accelerate trials, and provide particularly strong power gains for MCD tests.
背景癌症筛查试验需要大量样本和较长的时间跨度来证明癌症死亡率的降低,而这正是癌症筛查的主要目标。我们研究了利用对照组标本测试信息的假设和潜在功率增益,我们称之为 "预期效应"(IE)分析,并在此详细说明。IE 分析尤其适用于可在控制臂储存标本上进行的检测,如用于多癌检测(MCD)的储存血液。方法 我们模拟了假设的 MCD 筛查试验,以比较标准分析与 IE 分析的功率和样本大小。在本文详述的两个假设下,我们对 3 项现有筛查试验(全国肺筛查试验 (NLST)、明尼苏达结肠癌控制研究 (MINN-FOBT-A) 和前列腺癌、肺癌、结直肠癌、卵巢癌筛查试验-结直肠部分 (PLCO-CRC))进行了 IE 分析预测。结果 与现有 3 项试验的标准分析相比,IE 设计可将癌症特异性死亡率 p 值降低 5 倍(NLST)、33 倍(MINN-FOBT-A)或 14,160 倍(PLCO-CRC),或者将样本量(90% 功率)减少 26%(NLST)、48%(MINN-FOBT-A)或 59%(PLCO-CRC)。对于潜在的 MCD 试验设计,标准分析需要每臂 100,000 例受试者才能达到 90% 的多癌症死亡率检测功率,而 IE 分析每臂只需 37,500-50,000 例受试者就能达到 90% 的检测功率,具体取决于对照臂检测阳性的假设。结论 在筛查试验的对照组中检测储存的标本以进行 IE 分析,可大大提高降低样本量或加速试验的功率,尤其可为多发性癌症检测提供更强的功率增益。
{"title":"Increasing power in screening trials by testing control-arm specimens: Application to multicancer detection screening","authors":"Hormuzd A Katki, Philip C Prorok, Philip E Castle, Lori M Minasian, Paul F Pinsky","doi":"10.1093/jnci/djae083","DOIUrl":"https://doi.org/10.1093/jnci/djae083","url":null,"abstract":"Background Cancer screening trials have required large sample-sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the “Intended Effect” (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control-arm, such as stored blood for multicancer detection (MCD) tests. Methods We simulated hypothetical MCD screening trials to compare power and sample-size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial (NLST), Minnesota Colon Cancer Control Study (MINN-FOBT-A), and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial—colorectal component (PLCO-CRC)). Results Compared to the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality p-values 5-fold (NLST), 33-fold (MINN-FOBT-A), or 14,160-fold (PLCO-CRC), or alternately, reduced sample-size (90% power) by 26% (NLST), 48% (MINN-FOBT-A), or 59% (PLCO-CRC). For potential MCD trial designs requiring 100,000 subjects per-arm to achieve 90% power for multi-cancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37,500-50,000 per arm, depending on assumptions concerning control-arm test-positives. Conclusions Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample-size or accelerate trials, and provide particularly strong power gains for MCD tests.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Housing Assistance Among Patients with Cancer: SEER-Medicare U.S. Department of Housing and Urban Development Data Linkage 癌症患者的住房援助:SEER-Medicare 美国住房和城市发展部数据链接
Pub Date : 2024-04-08 DOI: 10.1093/jnci/djae082
Craig Evan Pollack, Veronica Garrison, Taylor Johnson, Amanda L Blackford, Robert Banks, William Howe, K Robin Yabroff, Lindsey Enewold
Background Lack of stable and affordable housing is an important social determinant of health. Federal housing assistance may buffer against housing vulnerabilities among low-income households, but research examining the association of housing assistance and cancer care has been limited. We introduce a new linkage of SEER-Medicare and Housing and Urban Development (HUD) administrative data. Methods Individuals enrolled in HUD public and assisted housing programs 2006-2021 were linked with cancer diagnoses 2006-2019 identified in the SEER-Medicare data from 16 states using Match*Pro probabilistic linkage software. HUD administrative data include timing and type of housing assistance and verified household income. Medicare administrative data are available through 2020. Results A total of 335,490 unique individuals who received housing assistance matched to SEER-Medicare data at any point in time, including 156,794 that recieved housing assistance around the time of their diagnosis (at least 6 months prior to diagnosis until 6 months after diagnosis or death). A total of 63,251 persons with housing assistance at the time of their diagnosis were aged 66 years and older and continuously enrolled in Medicare Parts A and B fee-for-service, 12,035 with lung, 8,866 with breast, 7,261 with colorectal, and 4,703 with prostate cancer. Conclusions This novel data linkage will be available through the National Cancer Institute and can be used to explore the ways in which housing assistance is associated with cancer diagnosis, care, and outcomes, including the role of housing assistance status in potentially reducing or contributing to inequities across racialized and ethnic groups.
背景缺乏稳定且负担得起的住房是影响健康的一个重要社会决定因素。联邦住房补助可以缓解低收入家庭的住房问题,但对住房补助与癌症护理之间关系的研究却很有限。我们将 SEER-Medicare 与住房和城市发展部 (HUD) 的行政数据进行了新的链接。方法 使用 Match*Pro 概率关联软件将 2006-2021 年参加 HUD 公共和辅助住房计划的个人与 SEER-Medicare 数据中确定的 16 个州的 2006-2019 年癌症诊断结果联系起来。HUD 管理数据包括住房援助的时间和类型以及经核实的家庭收入。医疗保险管理数据可提供至 2020 年。结果 共有 335,490 人在任何时间点接受了与 SEER-Medicare 数据相匹配的住房援助,其中 156,794 人在诊断前后(诊断前至少 6 个月至诊断或死亡后 6 个月)接受了住房援助。共有 63,251 人在确诊时获得了住房补助,他们的年龄在 66 岁及以上,并连续参加了医疗保险 A 部分和 B 部分的付费服务,其中 12,035 人患有肺癌,8,866 人患有乳腺癌,7,261 人患有结肠直肠癌,4,703 人患有前列腺癌。结论 国家癌症研究所(National Cancer Institute)将提供这种新颖的数据链接,可用于探索住房援助与癌症诊断、护理和结果的关联方式,包括住房援助状况在可能减少或导致不同种族和族裔群体之间的不平等方面所起的作用。
{"title":"Housing Assistance Among Patients with Cancer: SEER-Medicare U.S. Department of Housing and Urban Development Data Linkage","authors":"Craig Evan Pollack, Veronica Garrison, Taylor Johnson, Amanda L Blackford, Robert Banks, William Howe, K Robin Yabroff, Lindsey Enewold","doi":"10.1093/jnci/djae082","DOIUrl":"https://doi.org/10.1093/jnci/djae082","url":null,"abstract":"Background Lack of stable and affordable housing is an important social determinant of health. Federal housing assistance may buffer against housing vulnerabilities among low-income households, but research examining the association of housing assistance and cancer care has been limited. We introduce a new linkage of SEER-Medicare and Housing and Urban Development (HUD) administrative data. Methods Individuals enrolled in HUD public and assisted housing programs 2006-2021 were linked with cancer diagnoses 2006-2019 identified in the SEER-Medicare data from 16 states using Match*Pro probabilistic linkage software. HUD administrative data include timing and type of housing assistance and verified household income. Medicare administrative data are available through 2020. Results A total of 335,490 unique individuals who received housing assistance matched to SEER-Medicare data at any point in time, including 156,794 that recieved housing assistance around the time of their diagnosis (at least 6 months prior to diagnosis until 6 months after diagnosis or death). A total of 63,251 persons with housing assistance at the time of their diagnosis were aged 66 years and older and continuously enrolled in Medicare Parts A and B fee-for-service, 12,035 with lung, 8,866 with breast, 7,261 with colorectal, and 4,703 with prostate cancer. Conclusions This novel data linkage will be available through the National Cancer Institute and can be used to explore the ways in which housing assistance is associated with cancer diagnosis, care, and outcomes, including the role of housing assistance status in potentially reducing or contributing to inequities across racialized and ethnic groups.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140538678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluating Colonoscopy Quality by Performing Provider Type 按医疗机构类型评估结肠镜检查质量
Pub Date : 2024-04-08 DOI: 10.1093/jnci/djae080
Emily Berry, Jeff Hostetter, Joseph Bachtold, Sarah Zamarripa, Keith E Argenbright
Background Colorectal Cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer death in the United States. Colonoscopy is an essential tool for screening, used both as a primary approach and follow-up to an abnormal stool-based CRC screening result. Colonoscopy quality is often measured with four key indicators: bowel preparation, cecal intubation, mean withdrawal time, and adenoma detection. Colonoscopies are most often performed by gastroenterologists (GI), however, in rural and medically underserved areas non-GI providers often perform colonoscopies. This study aims to evaluate the quality and safety of screening colonoscopies performed by non-GI providers, comparing their outcomes to those of GI providers. Methods Descriptive statistics were used to characterize the study population. Results for quality indicators were stratified by provider type and compared. Statistical significance was determined using p &lt; 0.05 as the threshold for all comparisons; all p-values were two-sided. Results No statistical difference was found when comparing performance by provider type. Median performance for gastroenterologists, general surgeons, and family medicine providers ranged form 98—100% for cecal intubation; 97.4—100% for bowel preparation; 57.4—88.9% for male adenoma detection rate; 47.7—62.13% for female adenoma detection rate; and 0:12:10—0:20:16 for mean withdrawal time. All provider types met and exceeded the goal metric for each of the quality indicators (p &lt; 0.001). In this analysis, non-GI providers can be expected to perform colonoscopies with similar quality to GI providers based on performance outcomes for the key quality metrics.
背景 大肠癌(CRC)是美国第三大确诊癌症和第二大癌症死因。结肠镜检查是筛查的重要工具,既可作为初筛方法,也可作为粪便异常 CRC 筛查结果的后续检查。结肠镜检查的质量通常用四个关键指标来衡量:肠道准备、盲肠插管、平均退出时间和腺瘤检测。结肠镜检查通常由消化内科医生(GI)进行,但在农村和医疗服务不足的地区,非 GI 医疗服务提供者通常也会进行结肠镜检查。本研究旨在评估非 GI 医疗机构进行结肠镜筛查的质量和安全性,并将其结果与 GI 医疗机构的结果进行比较。方法 使用描述性统计来描述研究人群的特征。根据医疗机构类型对质量指标的结果进行分层并进行比较。所有比较均以 p &lt; 0.05 为临界值,所有 p 值均为双侧。结果 在按医疗机构类型比较绩效时,未发现统计差异。消化内科医生、普外科医生和全科医生在盲肠插管方面的绩效中位数为 98%-100%;肠道准备方面为 97.4%-100%;男性腺瘤检出率为 57.4%-88.9%;女性腺瘤检出率为 47.7%-62.13%;平均退出时间为 0:12:10-0:20:16。所有类型的医疗服务提供者都达到或超过了每项质量指标的目标指标(p &lt; 0.001)。在这项分析中,根据关键质量指标的绩效结果,非消化道医疗服务提供者的结肠镜检查质量与消化道医疗服务提供者类似。
{"title":"Evaluating Colonoscopy Quality by Performing Provider Type","authors":"Emily Berry, Jeff Hostetter, Joseph Bachtold, Sarah Zamarripa, Keith E Argenbright","doi":"10.1093/jnci/djae080","DOIUrl":"https://doi.org/10.1093/jnci/djae080","url":null,"abstract":"Background Colorectal Cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer death in the United States. Colonoscopy is an essential tool for screening, used both as a primary approach and follow-up to an abnormal stool-based CRC screening result. Colonoscopy quality is often measured with four key indicators: bowel preparation, cecal intubation, mean withdrawal time, and adenoma detection. Colonoscopies are most often performed by gastroenterologists (GI), however, in rural and medically underserved areas non-GI providers often perform colonoscopies. This study aims to evaluate the quality and safety of screening colonoscopies performed by non-GI providers, comparing their outcomes to those of GI providers. Methods Descriptive statistics were used to characterize the study population. Results for quality indicators were stratified by provider type and compared. Statistical significance was determined using p &amp;lt; 0.05 as the threshold for all comparisons; all p-values were two-sided. Results No statistical difference was found when comparing performance by provider type. Median performance for gastroenterologists, general surgeons, and family medicine providers ranged form 98—100% for cecal intubation; 97.4—100% for bowel preparation; 57.4—88.9% for male adenoma detection rate; 47.7—62.13% for female adenoma detection rate; and 0:12:10—0:20:16 for mean withdrawal time. All provider types met and exceeded the goal metric for each of the quality indicators (p &amp;lt; 0.001). In this analysis, non-GI providers can be expected to perform colonoscopies with similar quality to GI providers based on performance outcomes for the key quality metrics.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140538616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alcohol and colorectal cancer risk subclassified by mutational signatures of DNA mismatch repair deficiency 根据 DNA 错配修复缺陷突变特征对酒精与结直肠癌风险进行亚分类
Pub Date : 2024-04-04 DOI: 10.1093/jnci/djae078
Aiping Fang, Tomotaka Ugai, Carino Gurjao, Rong Zhong, Zhenhua Liu, Xinyuan Zhang, Peilu Wang, Jonathan Nowak, Molin Wang, Marios Giannakis, Shuji Ogino, Xuehong Zhang, Edward Giovannucci
Background We examined whether the association between alcohol consumption and CRC incidence was stronger for tumors with higher contributions of defective MMR (dMMR)-related tumor mutational signatures (TMSs). Methods We used data from 227,916 men and women who participated in the Nurses’ Health Study (1980-2016), the Nurses’ Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2016). Dietary data was collected every 4 years through validated food frequency questionnaires. Relative contributions of two dMMR-related TMSs (c-dMMRa/SBS15 and c-dMMRb/SBS26) were quantified using whole-exome sequencing data in a subset of incident CRC cases. Duplication-method Cox proportional hazards regression models were used to assess the association between alcohol consumption and the risk of CRC subtypes according to different contributions of the TMSs. All statistical tests were 2-sided. Results We documented 825 incident CRC cases with available TMS data over 26-36 years of follow-up. The association between alcohol consumption and CRC incidence was stronger for tumors with higher contributions of c-dMMRb/SBS26 (P-heterogeneitytrend = 0.02) compared to tumors with lower contributions of this TMS. Compared with nondrinkers, drinkers with ≥15 g/d of alcohol had a high risk of c-dMMRb/SBS26-high CRC [multivariable-adjusted HR: 2.43 (95% CI: 1.55-3.82)], but not c-dMMRb/SBS26-low CRC [0.86 (95% CI: 0.57-1.28)] or c-dMMRb/SBS26-moderate CRC [1.14 (95% CI: 0.76-1.71)]. No significant differential associations were observed for c-dMMRa/SBS15 (P-heterogeneitytrend = 0.41). Conclusions High alcohol consumption was associated with an increased incidence of CRC containing higher contributions of c-dMMRb/SBS26, suggesting that alcohol consumption may be involved in colorectal carcinogenesis through the DNA mismatch repair pathway.
背景 我们研究了饮酒与 CRC 发病率之间的关系是否与肿瘤突变特征(TMSs)相关的有缺陷 MMR(dMMR)肿瘤的发病率更高有关。方法 我们使用了 227,916 名男性和女性参与护士健康研究(1980-2016 年)、护士健康研究 II(1991-2017 年)和健康专业人员随访研究(1986-2016 年)的数据。每 4 年通过有效的食物频率问卷收集一次饮食数据。利用全外显子组测序数据量化了两个与 dMMR 相关的 TMS(c-dMMRa/SBS15 和 c-dMMRb/SBS26)在部分 CRC 发病病例中的相对贡献。根据 TMSs 的不同贡献率,采用重复法 Cox 比例危险度回归模型评估饮酒与 CRC 亚型风险之间的关系。所有统计检验均为双侧检验。结果 我们在 26-36 年的随访中记录了 825 例有 TMS 数据的 CRC 发病病例。与c-dMMRb/SBS26贡献率较低的肿瘤相比,c-dMMRb/SBS26贡献率较高的肿瘤饮酒与CRC发病率之间的关联性更强(P-heterogeneitytrend = 0.02)。与不饮酒者相比,饮酒量≥15 克/天者患 c-dMMRb/SBS26 高 CRC 的风险较高[多变量调整 HR:2.43 (95% CI:1.55-3.82)],而患 c-dMMRb/SBS26 低 CRC [0.86 (95% CI:0.57-1.28)] 或 c-dMMRb/SBS26 中等 CRC [1.14 (95% CI:0.76-1.71)]的风险较低。c-dMMRa/SBS15 没有观察到明显的差异关联(P-heterogeneitytrend = 0.41)。结论 大量饮酒与 CRC 发病率增加有关,其中 c-dMMRb/SBS26 的贡献率较高,这表明饮酒可能通过 DNA 错配修复途径参与结直肠癌的发生。
{"title":"Alcohol and colorectal cancer risk subclassified by mutational signatures of DNA mismatch repair deficiency","authors":"Aiping Fang, Tomotaka Ugai, Carino Gurjao, Rong Zhong, Zhenhua Liu, Xinyuan Zhang, Peilu Wang, Jonathan Nowak, Molin Wang, Marios Giannakis, Shuji Ogino, Xuehong Zhang, Edward Giovannucci","doi":"10.1093/jnci/djae078","DOIUrl":"https://doi.org/10.1093/jnci/djae078","url":null,"abstract":"Background We examined whether the association between alcohol consumption and CRC incidence was stronger for tumors with higher contributions of defective MMR (dMMR)-related tumor mutational signatures (TMSs). Methods We used data from 227,916 men and women who participated in the Nurses’ Health Study (1980-2016), the Nurses’ Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2016). Dietary data was collected every 4 years through validated food frequency questionnaires. Relative contributions of two dMMR-related TMSs (c-dMMRa/SBS15 and c-dMMRb/SBS26) were quantified using whole-exome sequencing data in a subset of incident CRC cases. Duplication-method Cox proportional hazards regression models were used to assess the association between alcohol consumption and the risk of CRC subtypes according to different contributions of the TMSs. All statistical tests were 2-sided. Results We documented 825 incident CRC cases with available TMS data over 26-36 years of follow-up. The association between alcohol consumption and CRC incidence was stronger for tumors with higher contributions of c-dMMRb/SBS26 (P-heterogeneitytrend = 0.02) compared to tumors with lower contributions of this TMS. Compared with nondrinkers, drinkers with ≥15 g/d of alcohol had a high risk of c-dMMRb/SBS26-high CRC [multivariable-adjusted HR: 2.43 (95% CI: 1.55-3.82)], but not c-dMMRb/SBS26-low CRC [0.86 (95% CI: 0.57-1.28)] or c-dMMRb/SBS26-moderate CRC [1.14 (95% CI: 0.76-1.71)]. No significant differential associations were observed for c-dMMRa/SBS15 (P-heterogeneitytrend = 0.41). Conclusions High alcohol consumption was associated with an increased incidence of CRC containing higher contributions of c-dMMRb/SBS26, suggesting that alcohol consumption may be involved in colorectal carcinogenesis through the DNA mismatch repair pathway.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140348980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of the National Cancer Institute
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1