Daniel J Zheng,Shalini Bhatia,Sedigheh Mirzaei,Richard Aplenc,Gregory T Armstrong,Kira Bona,Tara M Brinkman,Pim Brouwers,Kim Edelstein,Kelly Getz,I-Chan Huang,Anne C Kirchhoff,Sogol Mostoufi-Moab,Elyse R Park,Claire Snyder,K Robin Yabroff,Yutaka Yasui,Kevin Krull,Paul C Nathan
More than 60% of adult survivors of childhood cancer report medical financial hardship due to the cumulative costs of cancer-directed therapy and related chronic health conditions. Whether neurocognitive impairment as a late effect is associated with increased financial hardship is unknown. In a large national cohort of 3023 adult survivors of childhood cancer, we observed a dose-dependent relationship between neurocognitive impairment and financial hardship outcomes. Individuals with 4 impaired neurocognitive domains had over 3-fold increased odds of debt collection (OR = 3.12, 95% CI = 1.91-5.09) and bankruptcy (OR = 3.77, 95% CI = 2.01-7.07) compared to individuals with no impaired neurocognitive domains. After adjusting for education, employment, and household income, the independent association between neurocognitive impairment and financial hardship outcomes persisted suggesting that other mechanisms may be at play. Neurocognitive impairment is an important risk factor for medical financial hardship in this patient population and should be considered for targeted screening and intervention.
由于针对癌症的治疗和相关慢性健康状况的累积费用，60%以上的儿童癌症成年幸存者报告了医疗经济困难。神经认知障碍作为一种晚期效应是否与经济困难增加有关尚不清楚。在一个由3023名儿童癌症成年幸存者组成的大型国家队列中，我们观察到神经认知障碍和经济困难结果之间的剂量依赖关系。有4个神经认知域受损的个体与没有神经认知域受损的个体相比，债务追讨（OR = 3.12, 95% CI = 1.91-5.09）和破产（OR = 3.77, 95% CI = 2.01-7.07）的几率增加了3倍以上。在对教育、就业和家庭收入进行调整后，神经认知障碍和经济困难结果之间的独立关联仍然存在，这表明可能有其他机制在起作用。神经认知障碍是该患者群体医疗经济困难的重要危险因素，应考虑进行有针对性的筛查和干预。
{"title":"Neurocognitive impairment and financial hardship in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.","authors":"Daniel J Zheng,Shalini Bhatia,Sedigheh Mirzaei,Richard Aplenc,Gregory T Armstrong,Kira Bona,Tara M Brinkman,Pim Brouwers,Kim Edelstein,Kelly Getz,I-Chan Huang,Anne C Kirchhoff,Sogol Mostoufi-Moab,Elyse R Park,Claire Snyder,K Robin Yabroff,Yutaka Yasui,Kevin Krull,Paul C Nathan","doi":"10.1093/jnci/djaf383","DOIUrl":"https://doi.org/10.1093/jnci/djaf383","url":null,"abstract":"More than 60% of adult survivors of childhood cancer report medical financial hardship due to the cumulative costs of cancer-directed therapy and related chronic health conditions. Whether neurocognitive impairment as a late effect is associated with increased financial hardship is unknown. In a large national cohort of 3023 adult survivors of childhood cancer, we observed a dose-dependent relationship between neurocognitive impairment and financial hardship outcomes. Individuals with 4 impaired neurocognitive domains had over 3-fold increased odds of debt collection (OR = 3.12, 95% CI = 1.91-5.09) and bankruptcy (OR = 3.77, 95% CI = 2.01-7.07) compared to individuals with no impaired neurocognitive domains. After adjusting for education, employment, and household income, the independent association between neurocognitive impairment and financial hardship outcomes persisted suggesting that other mechanisms may be at play. Neurocognitive impairment is an important risk factor for medical financial hardship in this patient population and should be considered for targeted screening and intervention.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095482","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}
Matthew C Ward, Jung Julie Kang, Nabil F Saba, Shauna R Campbell, Neal S Akhave, Steven S Chang, Sharon A Spencer, Anna Spreafico, Glenn J Hanna, Sue S Yom, Dwight E Heron
Despite decades of progress in the treatment of head and neck cancer, recurrence and second primary cancers continue to occur. The management of non-metastatic, locoregionally recurrent or second primary cancers is a complex multidisciplinary challenge that often occurs without guidance from robust clinical trials. In 2023, the NRG Oncology cooperative group created the Recurrent and Metastatic Working Group with the express directive to investigate how resources could optimally address the key questions for the recurrent and metastatic populations. Here, we present our view of the state of the science and present considerations for future investigations.
{"title":"Salvage of locoregionally recurrent head and neck cancer: an NRG oncology working group review","authors":"Matthew C Ward, Jung Julie Kang, Nabil F Saba, Shauna R Campbell, Neal S Akhave, Steven S Chang, Sharon A Spencer, Anna Spreafico, Glenn J Hanna, Sue S Yom, Dwight E Heron","doi":"10.1093/jnci/djag025","DOIUrl":"https://doi.org/10.1093/jnci/djag025","url":null,"abstract":"Despite decades of progress in the treatment of head and neck cancer, recurrence and second primary cancers continue to occur. The management of non-metastatic, locoregionally recurrent or second primary cancers is a complex multidisciplinary challenge that often occurs without guidance from robust clinical trials. In 2023, the NRG Oncology cooperative group created the Recurrent and Metastatic Working Group with the express directive to investigate how resources could optimally address the key questions for the recurrent and metastatic populations. Here, we present our view of the state of the science and present considerations for future investigations.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101406","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}
{"title":"Could clearance of HPV open the door to HIV?","authors":"Alexandra de Pokomandy","doi":"10.1093/jnci/djaf380","DOIUrl":"https://doi.org/10.1093/jnci/djaf380","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069877","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}
Kerry S Courneya, Christopher M Booth, Janette L Vardy, Christine M Friedenreich, Haryana M Dhillon, Victoria Coyle, Kristin L Campbell, Fernanda Z Arthuso, Jane Turner, David E Kent, Caryl Russell, Julianne J Gordon, Joseph Henson, Neil S Chua, Derek J Jonker, Shelley Kay, Sharlene Gill, Patti O’Brien, Dongsheng Tu, Christopher J O’Callaghan
Background CHALLENGE was the first phase 3 trial to examine the effects of exercise on cancer-related survival and, therefore, required a substantial and sustained increase in moderate-to-vigorous physical activity (MVPA) that had not been achieved in previous trials. Here, we report the effects of the intervention on the social cognitive beliefs that were targeted to achieve long-term exercise behavior change. Methods Patients with resected colon cancer who had completed chemotherapy were randomized to health education materials (HEM) or a structured exercise program (SEP) consisting of 48 behavioral support sessions delivered over a 3-year period. Social cognitive constructs from the Theory of Planned Behavior were assessed by single items using 5-point scales at baseline and every 6 months during the 3-year intervention. Regression models for repeated measurements were used to estimate the least square means and robust standard errors for each randomized group at each time point. Results Between 2009 and 2024, 889 patients were randomized to SEP (n = 445) or HEM (n = 444). SEP compared to HEM reported significantly more favorable social cognitive beliefs about exercise at almost all time points. Average intervention effects (AIE) across the 3-year intervention favored SEP for perceived benefit (AIE = 0.29; p < .001), enjoyment (AIE = 0.40; p < .001), difficulty (AIE=-0.18; p = .003), confidence (AIE = 0.28; p < .001), support (AIE = 0.59; p < .001), motivation (AIE = 0.47; p < .001), opportunity (AIE = 0.31; p < .001), and planning (AIE = 0.82; p < .001). All social cognitive variables were significantly associated with self-reported MVPA at all time points. Conclusions The SEP intervention in the CHALLENGE trial successfully targeted the social cognitive beliefs that were associated with sustained MVPA. NCT00819208.
CHALLENGE是第一个检查运动对癌症相关生存影响的3期试验，因此，需要大量和持续地增加中等至高强度的体育活动（MVPA），这在以前的试验中没有实现。在这里，我们报告了干预对旨在实现长期运动行为改变的社会认知信念的影响。方法将完成化疗的结肠癌切除术患者随机分为健康教育材料组（HEM）和结构化锻炼计划组（SEP），其中包括48个行为支持课程，为期3年。计划行为理论的社会认知构念在基线时采用单项5分量表进行评估，在3年干预期间每6个月进行一次评估。使用重复测量的回归模型估计每个随机分组在每个时间点的最小二乘均值和稳健标准误差。结果2009 - 2024年，889例患者随机分为SEP组（n = 445）和HEM组（n = 444）。与HEM相比，SEP在几乎所有时间点都报告了更有利的运动社会认知信念。3年干预的平均干预效应（AIE）偏向于SEP的感知获益（AIE = 0.29; p <）。001)，享受(AIE = 0.40; p <；。001)，难度（AIE=-0.18; p = 0.003），置信度(AIE= 0.28; p <；。001)，支持(AIE = 0.59; p <；。001)，动机(AIE = 0.47; p <；。001)，机会(AIE = 0.31; p <；。001)和计划（AIE = 0.82; p < .001）。所有社会认知变量在所有时间点都与自我报告的MVPA显著相关。结论：在CHALLENGE试验中，SEP干预成功地靶向了与持续MVPA相关的社会认知信念。NCT00819208。
{"title":"Effects of a structured exercise program on motivational outcomes in patients with Colon cancer","authors":"Kerry S Courneya, Christopher M Booth, Janette L Vardy, Christine M Friedenreich, Haryana M Dhillon, Victoria Coyle, Kristin L Campbell, Fernanda Z Arthuso, Jane Turner, David E Kent, Caryl Russell, Julianne J Gordon, Joseph Henson, Neil S Chua, Derek J Jonker, Shelley Kay, Sharlene Gill, Patti O’Brien, Dongsheng Tu, Christopher J O’Callaghan","doi":"10.1093/jnci/djag023","DOIUrl":"https://doi.org/10.1093/jnci/djag023","url":null,"abstract":"Background CHALLENGE was the first phase 3 trial to examine the effects of exercise on cancer-related survival and, therefore, required a substantial and sustained increase in moderate-to-vigorous physical activity (MVPA) that had not been achieved in previous trials. Here, we report the effects of the intervention on the social cognitive beliefs that were targeted to achieve long-term exercise behavior change. Methods Patients with resected colon cancer who had completed chemotherapy were randomized to health education materials (HEM) or a structured exercise program (SEP) consisting of 48 behavioral support sessions delivered over a 3-year period. Social cognitive constructs from the Theory of Planned Behavior were assessed by single items using 5-point scales at baseline and every 6 months during the 3-year intervention. Regression models for repeated measurements were used to estimate the least square means and robust standard errors for each randomized group at each time point. Results Between 2009 and 2024, 889 patients were randomized to SEP (n = 445) or HEM (n = 444). SEP compared to HEM reported significantly more favorable social cognitive beliefs about exercise at almost all time points. Average intervention effects (AIE) across the 3-year intervention favored SEP for perceived benefit (AIE = 0.29; p &lt; .001), enjoyment (AIE = 0.40; p &lt; .001), difficulty (AIE=-0.18; p = .003), confidence (AIE = 0.28; p &lt; .001), support (AIE = 0.59; p &lt; .001), motivation (AIE = 0.47; p &lt; .001), opportunity (AIE = 0.31; p &lt; .001), and planning (AIE = 0.82; p &lt; .001). All social cognitive variables were significantly associated with self-reported MVPA at all time points. Conclusions The SEP intervention in the CHALLENGE trial successfully targeted the social cognitive beliefs that were associated with sustained MVPA. NCT00819208.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071494","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}
Christian P Kratz,Megan N Frone,Payal P Khincha,Jessica N Hatton,Judith Penkert,Paul A James,Amanda B Spurdle,Cristina Fortuno
TP53 germline pathogenic variants are among the most significant genetic causes of cancer across all age groups. Current TP53 variant classification guidelines are designed to identify high penetrance TP53 variants that lead to a phenotype called Li-Fraumeni syndrome. However, they are insufficient to accurately classify variants conferring atypical penetrance. These atypical penetrance variants are disease-causing, but the phenotype is often attenuated. Using current TP53 variant classification guidelines, atypical penetrance variants are not properly recognized leading to sub-optimal management of individuals carrying such variants. We highlight the need to develop strategies to consistently identify atypical penetrance disease-causing germline TP53 variants including development of variant classification specifications tailored to distinguish such variants, and to define the associated cancer spectrum and age-related risks. These studies will inform modifications to the existing standard risk management recommendations.
{"title":"Urgent need to recognize that Disease-Causing TP53 variants with atypical penetrance require distinct clinical recommendations.","authors":"Christian P Kratz,Megan N Frone,Payal P Khincha,Jessica N Hatton,Judith Penkert,Paul A James,Amanda B Spurdle,Cristina Fortuno","doi":"10.1093/jnci/djag015","DOIUrl":"https://doi.org/10.1093/jnci/djag015","url":null,"abstract":"TP53 germline pathogenic variants are among the most significant genetic causes of cancer across all age groups. Current TP53 variant classification guidelines are designed to identify high penetrance TP53 variants that lead to a phenotype called Li-Fraumeni syndrome. However, they are insufficient to accurately classify variants conferring atypical penetrance. These atypical penetrance variants are disease-causing, but the phenotype is often attenuated. Using current TP53 variant classification guidelines, atypical penetrance variants are not properly recognized leading to sub-optimal management of individuals carrying such variants. We highlight the need to develop strategies to consistently identify atypical penetrance disease-causing germline TP53 variants including development of variant classification specifications tailored to distinguish such variants, and to define the associated cancer spectrum and age-related risks. These studies will inform modifications to the existing standard risk management recommendations.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033562","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}
Gustavo Adolfo Pimentel-Parra,Nelia Soto-Ruiz,Paula Escalada-Hernández,Leticia San Martín-Rodríguez,Cristina García-Vivar
BACKGROUNDDigital health interventions have shown promise for improving quality of life, especially in the short term after treatment. However, evidence regarding long-term breast cancer survivors (LT-BCSs; disease free >5 years) remains limited. This study aimed to evaluate the effectiveness of an eHealth intervention targeting health promotion and late sequelae management to improve LT-BCSs' quality of life.METHODSIn a randomized controlled clinical trial, 201 LT-BCSs (mean 11 years posttreatment) were randomly assigned to an interventio group (n = 102) using the CUMACA-M mobile application with specific health advice and recommendations for LT-BCSs, or a control group (n = 99) receiving usual care. Quality of life was measured with the Quality of Life-Cancer Survivors scale (QOL-CS) at baseline and after 3 months. Analyses followed an intention-to-treat approach using t-tests, nonparametric tests, and effect sizes.RESULTSAt three months, no statistically or clinically significant differences between the groups in the overall quality of life score (QOL-CS) were found (difference of differences = 0.11; 95% CI -0.10 to 0.32; p = .303). In the intervention group, a small intragroup decrease in spiritual well-being was observed -0.25 (-0.49 to -0.02), of uncertain clinical significance; no significant differences between groups were detected.CONCLUSIONSThis eHealth intervention did not improve the quality of life of LT-BCSs, suggesting that more personalized, interactive, or professionally supported strategies may be needed. Future research should evaluate the long-term outcomes and effectiveness of hybrid or personalized digital strategies in this population.TRIAL REGISTRATIONClinicalTrials.gov NCT05322460; https://clinicaltrials.gov/study/NCT05322460.
{"title":"EHealth intervention for quality of life in long-term breast cancer survivors: Randomized controlled trial.","authors":"Gustavo Adolfo Pimentel-Parra,Nelia Soto-Ruiz,Paula Escalada-Hernández,Leticia San Martín-Rodríguez,Cristina García-Vivar","doi":"10.1093/jnci/djag020","DOIUrl":"https://doi.org/10.1093/jnci/djag020","url":null,"abstract":"BACKGROUNDDigital health interventions have shown promise for improving quality of life, especially in the short term after treatment. However, evidence regarding long-term breast cancer survivors (LT-BCSs; disease free >5 years) remains limited. This study aimed to evaluate the effectiveness of an eHealth intervention targeting health promotion and late sequelae management to improve LT-BCSs' quality of life.METHODSIn a randomized controlled clinical trial, 201 LT-BCSs (mean 11 years posttreatment) were randomly assigned to an interventio group (n = 102) using the CUMACA-M mobile application with specific health advice and recommendations for LT-BCSs, or a control group (n = 99) receiving usual care. Quality of life was measured with the Quality of Life-Cancer Survivors scale (QOL-CS) at baseline and after 3 months. Analyses followed an intention-to-treat approach using t-tests, nonparametric tests, and effect sizes.RESULTSAt three months, no statistically or clinically significant differences between the groups in the overall quality of life score (QOL-CS) were found (difference of differences = 0.11; 95% CI -0.10 to 0.32; p = .303). In the intervention group, a small intragroup decrease in spiritual well-being was observed -0.25 (-0.49 to -0.02), of uncertain clinical significance; no significant differences between groups were detected.CONCLUSIONSThis eHealth intervention did not improve the quality of life of LT-BCSs, suggesting that more personalized, interactive, or professionally supported strategies may be needed. Future research should evaluate the long-term outcomes and effectiveness of hybrid or personalized digital strategies in this population.TRIAL REGISTRATIONClinicalTrials.gov NCT05322460; https://clinicaltrials.gov/study/NCT05322460.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044565","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}
Boris Freidlin,Malcolm A Smith,Carmen J Allegra,Edward L Korn
Improvements in cancer treatment are guided by randomized clinical trials (RCTs) that reliably assess the therapeutic impact of adding experimental treatments into clinical practice. The fundamental value of RCTs is that the difference in outcomes between the experimental and control arms provides an unbiased estimate of the risk-benefit ratio for the experimental treatment. However, the clinical relevance of trial results depends on the control arm accurately reflecting the appropriate standard of care (SOC) in the intended-use population. Due to the accelerating pace of cancer treatment development, it is becoming more common for the SOC to change during an ongoing randomized trial. This increasingly dynamic SOC landscape may have a nontrivial impact on the conduct and interpretation of future RCTs, and thus it is important to appreciate these issues and, when possible, prospectively address them when designing and conducting clinical trials. We review common scenarios where the SOC changes and provide recommendations on how to design a trial to minimize the impact of such changes when the trial is ongoing.
{"title":"Changing standard of care during a randomized trial: examples, considerations and guidelines.","authors":"Boris Freidlin,Malcolm A Smith,Carmen J Allegra,Edward L Korn","doi":"10.1093/jnci/djag022","DOIUrl":"https://doi.org/10.1093/jnci/djag022","url":null,"abstract":"Improvements in cancer treatment are guided by randomized clinical trials (RCTs) that reliably assess the therapeutic impact of adding experimental treatments into clinical practice. The fundamental value of RCTs is that the difference in outcomes between the experimental and control arms provides an unbiased estimate of the risk-benefit ratio for the experimental treatment. However, the clinical relevance of trial results depends on the control arm accurately reflecting the appropriate standard of care (SOC) in the intended-use population. Due to the accelerating pace of cancer treatment development, it is becoming more common for the SOC to change during an ongoing randomized trial. This increasingly dynamic SOC landscape may have a nontrivial impact on the conduct and interpretation of future RCTs, and thus it is important to appreciate these issues and, when possible, prospectively address them when designing and conducting clinical trials. We review common scenarios where the SOC changes and provide recommendations on how to design a trial to minimize the impact of such changes when the trial is ongoing.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044563","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}
BACKGROUNDLung adenocarcinoma (LUAD) is the most common type of lung cancer. A recent genome-wide association study (GWAS) of LUAD in East Asia reported 28 independent susceptibility variants across 25 loci and identified 2 genes whose genetically predicted expression levels are associated with LUAD risk, using an ancestry-matched lung tissue expression quantitative trait loci (eQTL) dataset. It is desirable to identify additional susceptibility loci and to understand their underlying biological mechanisms.METHODSUsing an expanded GWAS of LUAD in East Asia and ancestry-matched lung tissue eQTL and DNA methylation QTL datasets, we performed transcriptome-wide association studies and DNA methylome-wide association studies simultaneously and examined the association between measured expression of genes and DNA methylation of nearby CpGs (eQTM). Genes and nearby CpGs are termed CpG-gene-LUAD trios if these three associations hold simultaneously.RESULTSAt Bonferroni-corrected P < .05, we identified a new susceptibility locus (6p21.31; lead SNP rs7772643), 10 LUAD-associated genes and 86 LUAD-associated CpGs. At false discovery rate q < 0.05, we identified 28 LUAD-associated genes, 220 LUAD-associated CpGs, and 45 CpG-gene-LUAD trios; among them, 43 were direction-matched regarding these three associations. These show that 23 of the known 28 susceptibility variants for LUAD in East Asia are near these genes or CpGs and MARCH3, ELF5, IKZF3, GSDMB, CCDC116, and DSP are putative novel susceptibility loci. Few of them was reported in LUAD in European populations.CONCLUSIONSThis study substantially advances our understanding of the etiology of LUAD in East Asia and could be useful in developing translational applications.
肺腺癌（LUAD）是最常见的肺癌类型。最近一项东亚地区LUAD全基因组关联研究（GWAS）报告了25个基因座中的28个独立易感变异，并使用一个谱系匹配的肺组织表达数量性状位点（eQTL）数据集确定了2个基因，其遗传预测表达水平与LUAD风险相关。需要确定其他易感位点并了解其潜在的生物学机制。方法利用扩大的东亚LUAD GWAS和祖先匹配的肺组织eQTL和DNA甲基化QTL数据集，同时进行转录组全关联研究和DNA甲基化全关联研究，并检测所测基因表达与附近CpGs DNA甲基化（eQTM）之间的关系。如果这三种关联同时存在，基因和附近的cpg被称为cpg -基因- luad三重奏。结果sat Bonferroni-corrected P <。2005年，我们发现了一个新的易感位点（6p21.31; lead SNP rs7772643）， 10个luad相关基因和86个luad相关CpGs。在错误发现率q < 0.05的情况下，我们鉴定出28个与luad相关的基因，220个与luad相关的cpg，以及45个cpg基因- luad三元组；其中43例在这三种关联上方向匹配。这些结果表明，东亚地区已知的28个LUAD易感变异中有23个接近这些基因或CpGs，而MARCH3、ELF5、IKZF3、GSDMB、CCDC116和DSP是推测的新的易感位点。在欧洲人群的LUAD中很少有报道。结论本研究极大地促进了我们对东亚LUAD病因的理解，并可用于开发翻译应用。
{"title":"Identifying expression and DNA methylation biomarkers for lung adenocarcinoma risk in East Asia.","authors":"Tzu-Yu Chen,Li-Hsin Chien,Shih Sheng Jiang,Jiyeon Choi,Hsiao-Han Hung,Chin-Fu Hsiao,Jianxin Shi,Batel Blechter,Charles E Breeze,Gee-Chen Chang,Kuan-Yu Chen,Ying-Huang Tsai,Wu-Chou Su,Ming-Shyan Huang,Yuh-Min Chen,Yueh-Feng Wen,Chung-Yu Chen,Chih-Liang Wang,Fang-Yu Tsai,Hui-Ling Chen,Wan-Shan Hsieh,Hsien-Chih Lin,Lu-Hai Wang,Chien-Jen Chen,Pan-Chyr Yang,Chih-Yi Chen,Nathaniel Rothman,Stephen J Chanock,Qing Lan,I-Shou Chang,Chao A Hsiung","doi":"10.1093/jnci/djag021","DOIUrl":"https://doi.org/10.1093/jnci/djag021","url":null,"abstract":"BACKGROUNDLung adenocarcinoma (LUAD) is the most common type of lung cancer. A recent genome-wide association study (GWAS) of LUAD in East Asia reported 28 independent susceptibility variants across 25 loci and identified 2 genes whose genetically predicted expression levels are associated with LUAD risk, using an ancestry-matched lung tissue expression quantitative trait loci (eQTL) dataset. It is desirable to identify additional susceptibility loci and to understand their underlying biological mechanisms.METHODSUsing an expanded GWAS of LUAD in East Asia and ancestry-matched lung tissue eQTL and DNA methylation QTL datasets, we performed transcriptome-wide association studies and DNA methylome-wide association studies simultaneously and examined the association between measured expression of genes and DNA methylation of nearby CpGs (eQTM). Genes and nearby CpGs are termed CpG-gene-LUAD trios if these three associations hold simultaneously.RESULTSAt Bonferroni-corrected P < .05, we identified a new susceptibility locus (6p21.31; lead SNP rs7772643), 10 LUAD-associated genes and 86 LUAD-associated CpGs. At false discovery rate q < 0.05, we identified 28 LUAD-associated genes, 220 LUAD-associated CpGs, and 45 CpG-gene-LUAD trios; among them, 43 were direction-matched regarding these three associations. These show that 23 of the known 28 susceptibility variants for LUAD in East Asia are near these genes or CpGs and MARCH3, ELF5, IKZF3, GSDMB, CCDC116, and DSP are putative novel susceptibility loci. Few of them was reported in LUAD in European populations.CONCLUSIONSThis study substantially advances our understanding of the etiology of LUAD in East Asia and could be useful in developing translational applications.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044569","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}
Lauren S Lowe,Dylan K Kim,Christine H Rohde,James B Yu,Simon K Cheng,Lisa A Kachnic,David P Horowitz,Alfred I Neugut,Connor J Kinslow
In 2020, the Food and Drug Administration mandated a black box warning on all breast implants, warning of an association with anaplastic large cell lymphoma (ALCL). The World Health Organization recently introduced breast implant-associated ALCL (BIA-ALCL) as a new provisional entity. We identified BIA-ALCL cases diagnosed in adult women, 1/1/2021-12/31/2022, following the inaugural use of the new diagnostic code within the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Age-adjusted incidence was calculated to the 2000 U.S. standard population. The age-adjusted incidence rate of BIA-ALCL in 2021 and 2022 was 17.2 (95% CI, 7.6-33.8) and 26.9 (95% CI, 14.8-45.5) per 100 million person-years, respectively; increased compared to our prior estimate for 2012-2018 (14.5 to 19.6 cases/100 million person-years) and substantially exceeding the FDA's earlier estimate for 2001-2007 (3 cases/100 million persons-years). This study presents the first population-based incidence rate estimations of BIA-ALCL, which is increasing rapidly in the U.S.
2020年，美国食品和药物管理局（Food and Drug Administration，简称fda）要求所有隆胸植入物都贴上黑框警告，警告其与间变性大细胞淋巴瘤（ALCL）有关。世界卫生组织最近将乳房植入物相关ALCL （BIA-ALCL）作为一个新的临时实体引入。在美国国家癌症研究所的监测、流行病学和最终结果项目中首次使用新的诊断代码后，我们确定了2021年1月1日至2022年12月31日在成年女性中诊断出的BIA-ALCL病例。年龄调整后的发病率计算至2000年美国标准的人口。2021年和2022年BIA-ALCL的年龄调整发病率分别为17.2 （95% CI, 7.6-33.8）和26.9 (95% CI, 14.8-45.5) / 1亿人年；与我们之前对2012-2018年的估计相比（14.5至19.6例/1亿人年）有所增加，并且大大超过了FDA先前对2001-2007年的估计（3例/1亿人年）。本研究首次提出了基于人群的BIA-ALCL发病率估计，该发病率在美国迅速增加
{"title":"Incidence of breast implant-associated anaplastic large cell lymphoma.","authors":"Lauren S Lowe,Dylan K Kim,Christine H Rohde,James B Yu,Simon K Cheng,Lisa A Kachnic,David P Horowitz,Alfred I Neugut,Connor J Kinslow","doi":"10.1093/jnci/djag019","DOIUrl":"https://doi.org/10.1093/jnci/djag019","url":null,"abstract":"In 2020, the Food and Drug Administration mandated a black box warning on all breast implants, warning of an association with anaplastic large cell lymphoma (ALCL). The World Health Organization recently introduced breast implant-associated ALCL (BIA-ALCL) as a new provisional entity. We identified BIA-ALCL cases diagnosed in adult women, 1/1/2021-12/31/2022, following the inaugural use of the new diagnostic code within the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Age-adjusted incidence was calculated to the 2000 U.S. standard population. The age-adjusted incidence rate of BIA-ALCL in 2021 and 2022 was 17.2 (95% CI, 7.6-33.8) and 26.9 (95% CI, 14.8-45.5) per 100 million person-years, respectively; increased compared to our prior estimate for 2012-2018 (14.5 to 19.6 cases/100 million person-years) and substantially exceeding the FDA's earlier estimate for 2001-2007 (3 cases/100 million persons-years). This study presents the first population-based incidence rate estimations of BIA-ALCL, which is increasing rapidly in the U.S.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021627","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}
Pianpian Cao, Koen De Nijs, Justin Lee, Jihyoun Jeon, Harry J De Koning, Sylvia K Plevritis, Kevin Ten Haaf, Summer S Han, Rafael Meza
Background Replacing the pack-year criterion for lung cancer screening with smoking duration has been proposed to reduce racial disparities in eligibility. However, no studies have evaluated the potential long-term benefits and harms of Duration-based criteria. We conducted a comparative modeling study to evaluate the effectiveness of Duration-based eligibility versus that from current guidelines and other alternative criteria. Methods We used three CISNET models to evaluate the performance of Duration-based screening with various smoking duration thresholds (15-40 years in 5-year increments) for the 1960 and 1970 US birth cohorts. We first examined age-specific eligibility patterns of Duration-based strategies versus pack-year and risk-based criteria. We then evaluated the performance of different strategies, comparing the resulting number of screens, lung cancer deaths averted (LCDA), life-years gained (LYG), false-positive screens, and overdiagnosed cases. We compared the strategies’ efficiency using LCDA and LYG per screen and the benefit-to-harm ratios using LCDA and LYG per overdiagnosed case. Results Risk-based criteria resulted in the most LCDA and LYG but also in more overdiagnosed cases. Duration-based strategies with a 35-year cut-off achieved comparable LCDA and LYG to current US guidelines and resulted in similar false positive and overdiagnosed cases per screen. Duration-based scenarios with a 20-year cut-off required substantially more screenings but yielded only modest additional LCDA and LYG, resulting in lower benefits per screen than current guidelines. Conclusion Duration-based screening may be as efficient as current US guidelines. Given their potential to reduce disparities in eligibility shown in recent studies and simpler implementation, Duration-based criteria warrant consideration.
{"title":"Performance of smoking duration-based lung cancer screening eligibility criteria: a comparative modeling study","authors":"Pianpian Cao, Koen De Nijs, Justin Lee, Jihyoun Jeon, Harry J De Koning, Sylvia K Plevritis, Kevin Ten Haaf, Summer S Han, Rafael Meza","doi":"10.1093/jnci/djag018","DOIUrl":"https://doi.org/10.1093/jnci/djag018","url":null,"abstract":"Background Replacing the pack-year criterion for lung cancer screening with smoking duration has been proposed to reduce racial disparities in eligibility. However, no studies have evaluated the potential long-term benefits and harms of Duration-based criteria. We conducted a comparative modeling study to evaluate the effectiveness of Duration-based eligibility versus that from current guidelines and other alternative criteria. Methods We used three CISNET models to evaluate the performance of Duration-based screening with various smoking duration thresholds (15-40 years in 5-year increments) for the 1960 and 1970 US birth cohorts. We first examined age-specific eligibility patterns of Duration-based strategies versus pack-year and risk-based criteria. We then evaluated the performance of different strategies, comparing the resulting number of screens, lung cancer deaths averted (LCDA), life-years gained (LYG), false-positive screens, and overdiagnosed cases. We compared the strategies’ efficiency using LCDA and LYG per screen and the benefit-to-harm ratios using LCDA and LYG per overdiagnosed case. Results Risk-based criteria resulted in the most LCDA and LYG but also in more overdiagnosed cases. Duration-based strategies with a 35-year cut-off achieved comparable LCDA and LYG to current US guidelines and resulted in similar false positive and overdiagnosed cases per screen. Duration-based scenarios with a 20-year cut-off required substantially more screenings but yielded only modest additional LCDA and LYG, resulting in lower benefits per screen than current guidelines. Conclusion Duration-based screening may be as efficient as current US guidelines. Given their potential to reduce disparities in eligibility shown in recent studies and simpler implementation, Duration-based criteria warrant consideration.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032811","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}
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