Journal of the National Cancer Institute最新文献

{"title":"Targeting fusion oncoproteins in childhood cancers: Challenges and future opportunities for developing therapeutics","authors":"Sharad K Verma, Keren L Witkin, Anu Sharman, Malcolm A Smith","doi":"10.1093/jnci/djae075","DOIUrl":"https://doi.org/10.1093/jnci/djae075","url":null,"abstract":"Fusion oncoproteins are associated with childhood cancers and have proven challenging to target, aside from those that include kinases. As part of its efforts for targeting childhood cancers, the National Cancer Institute recently conducted a series on ‘Novel Chemical Approaches for Targeting Fusion Oncoproteins’. Key learnings on leading platforms and technologies which can be utilized to advance the development of molecular therapeutics that target fusion oncoproteins in childhood cancers are described. Recent breakthroughs in medicinal chemistry and chemical biology provide new ground and creative strategies to exploit for the development of targeted agents for improving outcomes against these recalcitrant cancers.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349152","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":"TP53-associated early breast cancer: new observations from a large cohort.","authors":"R. Sandoval, M. Bottosso, Tianyu Li, Natália Polidorio, Brittany L. Bychkovsky, B. Verret, A. Gennari, Sophie Cahill, M. Achatz, O. Caron, Marion Imbert-Bouteille, Catherine Noguès, Kara N Mawell, Cristina Fortuno, A. Spurdle, N. Tayob, Fabrice Andre, Judy E Garber","doi":"10.1093/jnci/djae074","DOIUrl":"https://doi.org/10.1093/jnci/djae074","url":null,"abstract":"BACKGROUND\u0000A large well-annotated recent international cohort of Li-Fraumeni (LFS) patients with early-stage breast cancer (BC) was examined for shared features.\u0000\u0000\u0000METHODS\u0000This multicentre cohort study included females with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic BC diagnosed between 2002-2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were utilized to summarize proportions and differences were assessed by Chi square or Wilcoxon rank sum tests. Metachronous contralateral breast cancer (CBC) risk, radiation-induced sarcoma risk, and recurrence-free survival (RFS) were analyzed by Kaplan-Meier methodology.\u0000\u0000\u0000RESULTS\u0000Among 227 females who met study criteria, the median age of first BC diagnosis was 37 years (range 21-71), 11.9% presented with bilateral synchronous BC and 18.1% had ductal carcinoma in situ (DCIS) only. In total, 166 (73.1%) underwent mastectomies including 67 bilateral mastectomies as first BC surgery. Among those with retained breast tissue, CBC rate was 25.3% at 5-years. Among 186 invasive tumors, 72.1% were stages I-II, 48.9% node-negative, and the most common subtypes were HR+/HER2- (40.9%) and HR+/HER2 + (34.4%). At a median follow-up of 69.9 months (IQR 32.6-125.9), invasive HR+/HER2- disease had the highest recurrence risk among the subtypes (5-year RFS 61.1%, p = .0012). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%.\u0000\u0000\u0000CONCLUSION\u0000We observed high rates of DCIS, HR+ and HER2+ breast cancers, with a worse outcome in the HR+/HER2- luminal tumors despite appropriate treatment. Confirmation of these findings in further studies could have implications for BC care in LFS.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"628 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140749398","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":"Multi-tissue transcriptome-wide association studies identified 235 genes for intrinsic subtypes of breast cancer","authors":"James L Li, Julian C McClellan, Haoyu Zhang, Guimin Gao, Dezheng Huo","doi":"10.1093/jnci/djae041","DOIUrl":"https://doi.org/10.1093/jnci/djae041","url":null,"abstract":"Background Although genome-wide association studies (GWAS) of breast cancer (BC) identified common variants which differ between intrinsic subtypes, genes through which these variants act to impact BC risk have not been fully established. Transcriptome-wide association studies (TWAS) have identified genes associated with overall BC risk, but subtype-specific differences are largely unknown. Methods We performed two multi-tissue TWASs for each BC intrinsic subtype including an expression-based approach that collated TWAS signals from expression quantitative trait loci (eQTLs) across multiple tissues and a novel splicing-based approach that collated signals from splicing QTLs (sQTLs) across intron clusters and subsequently across tissues. We utilized summary statistics for five intrinsic subtypes including Luminal A-like, Luminal B-like, Luminal B/HER2-negative-like, HER2-enriched-like, and Triple-negative BC, generated from 106,278 BC cases and 91,477 controls in the Breast Cancer Association Consortium. Results Overall, we identified 235 genes in 88 loci across were associated with at least one of the five intrinsic subtypes. Most genes were subtype-specific, and many have not been reported in previous TWAS. We discovered common variants that modulate expression of CHEK2 confer increased risk to Luminal-A-like BC, in contrast to the viewpoint that CHEK2 primarily harbors rare, penetrant mutations. Additionally, our splicing-based TWAS provided population-level support for MDM4 splice variants that increased triple-negative BC risk. Conclusion Our comprehensive, multi-tissue TWAS corroborated previous GWAS loci for overall BC risk and intrinsic subtypes, while underscoring how common variation which impacts expression and splicing of genes in multiple tissue types can be used to further elucidate the etiology of BC.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139943281","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":"Evaluating the sensitivity of EQ-5D-5L in patients with brain metastases: a secondary analysis of NRG CC001","authors":"Hua-Ren R Cherng, Melody Qu, Zafar Zafari, Søren Bentzen, Terri S Armstrong, Vinai Gondi, Paul D Brown, Minesh Mehta, Mark V Mishra","doi":"10.1093/jnci/djae020","DOIUrl":"https://doi.org/10.1093/jnci/djae020","url":null,"abstract":"BACKGROUND EuroQoL EQ-5D is a commonly used measure of health-related quality of life (HRQOL) in clinical trials given the use of its index score as a measure of health utilities. It is unclear whether EQ-5D is sensitive to changes in neurocognitive function and progression that occur following brain radiation. This study sought to evaluate the sensitivity of EQ-5D-5L in reflecting these changes. PATIENTS and METHODS A secondary analysis of NRG Oncology CC001 was performed. Mean EQ-5D-5L index and visual analog scale (VAS) score changes from baseline between groups of patients stratified by neurocognitive function and intracranial progression status were assessed. MD Anderson Symptom Inventory for brain tumor (MDASI-BT) symptom and interference items were also analyzed between groups. RESULTS EQ-5D-5L index and VAS score changes between patients who had cognitive failure and those that had preserved cognition showed no significant differences at any time point. In contrast, VAS changes at 4 (1.61 vs -5.13, P = .05) and 6 months (8.17 vs -0.14, P = .04) were significantly improved in the patients who survived without intracranial progression. MDASI-BT cognitive factor scores were significantly improved in the cohort of patients with preserved neurocognitive function at 2 (1.68 vs 2.08, P = .05) and 4 months (1.35 vs 1.83, P = .04). MDASI-BT symptom interference was significantly associated with intracranial progression at 4 months, but not with neurocognitive status. CONCLUSION EQ-5D-5L index and VAS scores were not sensitive to neurocognitive changes that patients experienced, but VAS scores were sensitive to progression. This study challenges the routine use of EQ-5D as a QoL metric in brain metastases clinical trials that are focused on preventing neurocognitive dysfunction. Trial Registration NCT# 02360215","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139568351","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":"Simulating the population impact of interventions to reduce racial gaps in breast cancer treatment","authors":"Juan Yanguela, Bradford E Jackson, Katherine E Reeder-Hayes, Mya L Roberson, Gabrielle B Rocque, Tzy-Mey Kuo, Matthew R LeBlanc, Christopher Baggett, Laura Green, Erin Laurie-Zehr, Stephanie B Wheeler","doi":"10.1093/jnci/djae019","DOIUrl":"https://doi.org/10.1093/jnci/djae019","url":null,"abstract":"Background Inequities in guideline-concordant treatment receipt contribute to worse survival in Black breast cancer (BCa) patients. Inequity-reduction interventions (eg, navigation, bias training, tracking dashboards) can close such treatment gaps. We simulated the population-level impact of statewide implementation of inequity-reduction interventions on racial BCa inequities in North Carolina. Methods Using registry-linked multi-payer claims data, we calculated Black/White inequities in endocrine (ET; n = 12,033) and chemotherapy (CTx; n = 1,819) receipt. We then built cohort- (ET and CTx), and race-stratified Markov models to simulate the potential increase in the proportion of patients receiving ET or CTx and subsequent improvements in BCa outcomes if inequity-reducing intervention were implemented statewide. We report uncertainty bounds representing 95% of simulation results. Results 75.6% and 72.1% of Black patients received ET and CTx over the 2006-2015 and 2004-2015 periods (vs 79.3 and 78.9% of White patients, respectively). Inequity-reduction interventions could increase ET and CTx receipt among Black patients to 89.9% (85.3, 94.6%) and 85.7% (80.7, 90.9%). Such interventions could also decrease 5-and 10-year BCa mortality gaps from 3.4 to 3.2 (3.0, 3.3) and from 6.7 to 6.1 (5.9, 6.4) percentage points in the ET cohorts and from 8.6 to 8.1 (7.7, 8.4) and from 8.2 to 7.8 (7.3, 8.1) percentage points in the CTx cohorts. Conclusions Inequity-focused interventions could improve cancer outcomes for Black patients. However, they would not fully close the racial BCa mortality gap. Addressing other inequities along cancer continuum (eg, screening, pre-and post-diagnosis risk factors) is required to achieve full equity in BCa outcomes.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"166 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139568340","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":"Increasing radiation therapy and lower survival for human papillomavirus–related oropharynx cancer associated with a shift to community cancer center care","authors":"Danielle R Trakimas, Wojtek Mydlarz, Leila J Mady, Wayne Koch, Harry Quon, Nyall R London, Carole Fakhry","doi":"10.1093/jnci/djad238","DOIUrl":"https://doi.org/10.1093/jnci/djad238","url":null,"abstract":"Background Studies have shown lower overall survival for patients with head and neck cancer treated at low-volume or community cancer centers. As the incidence of human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma steadily rises in the United States, we hypothesized that a greater proportion of patients with HPV-related oropharyngeal squamous cell carcinoma is being treated at community cancer centers, with a shift toward primary nonsurgical treatment. Methods This cohort study included patients from the US National Cancer Database who received a diagnosis of HPV-related oropharyngeal squamous cell carcinoma from 2010 to 2019 and underwent treatment at a community cancer center or academic cancer center. The proportion of patients with HPV-related oropharyngeal squamous cell carcinoma treated at community cancer centers and receiving primary nonsurgical treatment was analyzed over time. Four-year overall survival was compared between community cancer centers and academic cancer centers. Results The majority (67.4%) of 20 298 patients were treated at an academic cancer center, yet the proportion of patients treated at community cancer centers increased by 10% from 2010 to 2019 (P < .01 for trend). The proportion of patients undergoing primary nonsurgical treatment increased from 62.1% to 73.7% from 2010 to 2019 (P < .01 for trend), and patients were statistically significantly more likely to undergo nonsurgical treatment at community cancer centers than at academic cancer centers (adjusted odds ratio = 1.20, 95% confidence interval = 1.18 to 1.22). Treatment at community cancer centers was associated with worse survival overall (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09 to 1.31), specifically for patients receiving primary nonsurgical treatment (adjusted hazard ratio = 1.22, 95% confidence interval = 1.11 to 1.34). Conclusions Treatment of HPV-related oropharyngeal squamous cell carcinoma has recently shifted to community cancer centers, with an increase in the proportion of nonsurgical treatment and worse overall survival at these centers compared with academic cancer centers. Concentration of care for HPV-related oropharyngeal squamous cell carcinoma at academic cancer centers and dedicated head and neck cancer centers may increase access to all available treatment modalities and improve survival.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139081707","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":"Genetic Trio of BRAF and TERT Mutations and rs2853669TT in Papillary Thyroid Cancer Aggressiveness","authors":"Rengyun Liu, Guangwu Zhu, Jie Tan, Xiaopei Shen, Mingzhao Xing","doi":"10.1093/jnci/djad265","DOIUrl":"https://doi.org/10.1093/jnci/djad265","url":null,"abstract":"Background BRAF V600E and TERT promoter mutations are core components in current genetic-based risk assessment for precision management of papillary thyroid cancer (PTC). It remains unknown whether this could be refined to even better precision by a widely recognized prognostic single nucleotide polymorphism (SNP), rs2853669T>C, in the TERT promoter. Methods Genetic status of mutations and SNP were examined by sequencing genomic DNA from PTC in 608 patients (427 women and 181 men) aged 47 years (IQR 37-57), with a median follow-up time of 75 months (IQR 36 to 123), and their relationship with clinical outcomes was analyzed. Luciferase reporter assay was performed to examine TERT promoter activities. Results TERT promoter mutations showed a strong association with PTC recurrence in the presence of genotype TT of rs2853669 (adjusted HR = 2.12, 95% CI 1.10-4.12) but not TC/CC (adjusted HR = 1.17, 95% CI 0.56-2.41). TERT and BRAF mutations commonly coexisted and synergistically promoted PTC recurrence. With this genetic duet, TT of rs2853669 showed a robustly higher disease recurrence compared with TC/CC (adjusted HR = 14.26, 95% CI 2.86-71.25). Patients with the genetic trio of BRAF V600E, TERT mutation and TT of rs2853669 had a recurrence of 76.5% vs recurrence of 8.4% with neither mutation and with TC/CC (HR = 13.48, 95% CI 6.44-28.21). T allele of rs2853669 strongly increased TERT promoter, particularly the mutant promoter. Conclusions SNP rs2853669T>C dramatically refines the prognostic power of BRAF V600E and TERT promoter mutations to a higher precision, suggesting the need for including this SNP in the current genetic-based risk prognostication of PTC.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770869","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":"The Impact of Multidisciplinary Cancer Conferences on Overall Survival: A Meta-Analysis","authors":"Ryan S Huang, Andrew Mihalache, Abdulwadud Nafees, Asad Hasan, Xiang Y Ye, Zhihui Liu, Natasha B Leighl, Srinivas Raman","doi":"10.1093/jnci/djad268","DOIUrl":"https://doi.org/10.1093/jnci/djad268","url":null,"abstract":"Background Multidisciplinary cancer conferences (MCCs) are comprised of regular meetings between diverse specialists working together to share clinical decision making in cancer care. The aim of this study is to systematically review and meta-analyze the effect of MCC intervention on overall survival of cancer patients. Methods A systematic literature search was conducted on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials for studies published up to July 2023. Studies reporting on the impact of MCCs on overall survival of patients were included. A standard random effects model with the inverse-variance weighted approach was used to estimate the pooled hazard ratio of mortality (MCC vs non-MCC) across studies and the heterogeneity was assessed by I2. Publication bias was examined using funnel plot and Egger’s test. Results A total of 134,287 cancer patients from 59 studies were included in our analysis, with 48,467 managed by MCCs and 85,820 in the control arm. Across all cancer types, patients managed by MCCs had an increased overall survival compared to control patients (HR = 0.67, 95%CI = [0.62, 0.71], I2=84%). Median survival time was 30.2 months and 19.0 months in the MCC intervention and control group, respectively. In subgroup analysis, a positive effect of MCC intervention on overall survival was found in breast, colorectal, esophageal, haematological, hepatocellular, lung, pancreatic, and head and neck cancer. Conclusions Overall, our meta-analysis found a significant positive effect of MCCs compared to controls. Further studies are needed to establish nuanced guidelines when optimizing MCC integration for treating diverse cancer patient populations.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"203 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138822903","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":"Cancer Survivorship—A Framework for Quality Cancer Care","authors":"Bradley Zebrack","doi":"10.1093/jnci/djad266","DOIUrl":"https://doi.org/10.1093/jnci/djad266","url":null,"abstract":"When diagnosed with cancer or any other life-threatening condition, people must negotiate two once-separate but now integrated realms—a medical care industrial complex and an everyday life now lived in conscious awareness of mortality—a state of being subject to death. Life becomes a series of challenges and disruptions to relationships, body image and integrity, autonomy and independence, life goals, hopes, and dreams for the future. Whether one physically, emotionally, or spiritually survives, thrives, or succumbs to cancer is dependent upon a treatment plan that accounts for the multiple and varied ways in which people experience dual citizenship in the realms of the well and the sick. A theory of cancer survivorship that integrates both medical and patient perspectives into a cogent and coherent framework has the potential to enhance the quality of cancer care and the patient experience.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"35 6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770699","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":"Maternal serum concentrations of per- and polyfluoroalkyl substances and childhood acute lymphoblastic leukemia","authors":"Rena R Jones, Jessica M Madrigal, Rebecca Troisi, Heljä-Marja Surcel, Hanna Öhman, Juha Kivelä, Hannu Kiviranta, Panu Rantakokko, Jani Koponen, Danielle N Medgyesi, Katherine A McGlynn, Joshua Sampson, Paul S Albert, Mary H Ward","doi":"10.1093/jnci/djad261","DOIUrl":"https://doi.org/10.1093/jnci/djad261","url":null,"abstract":"Background Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia. Methods We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia (ALL) in full-term offspring (<15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother’s age, gestational age, birth order, and child’s sex. We analyzed continuous and categorical exposures, estimating odds ratios (OR) and 95% confidence intervals (CI) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child’s sex. Results N‑methyl‑perfluorooctane sulfonamidoacetic acid (MeFOSAA) was associated with ALL in continuous models (per each doubling in levels: ORperlog2=1.22, CI = 1.07-1.39), with a positive exposure-response across categories (OR>90th percentile=2.52, CI = 1.33-4.78; p-trend = 0.01). While we found no relationship with perfluorooctane sulfonic acid (PFOS) overall, an association was observed in samples collected 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2=4.01, CI = 1.62-9.93). A positive association with perfluorononanoic acid was suggested among first births (p-interaction = 0.06). The MeFOSAA association was mainly limited to children diagnosed before age 5 (p-interaction = 0.02). We found no consistent patterns of association with other PFAS, nor differences by sex. Conclusions These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of PFOS and with a precursor, MeFOSAA.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138679263","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}