JNCI Journal of the National Cancer Institute最新文献

{"title":"Prioritizing context-specific genetic risk mechanisms in 11 solid cancers.","authors":"Xueyao Wu, Artem Kim, Charles E Breeze, Tracy A O'Mara, Dhanya Ramachandran, Thilo Dörk, Stella Koutros, Nathaniel Rothman, Ludmila Prokunina-Olsson, Nicholas Mancuso, Sara Lindström, Peter Kraft","doi":"10.1093/jnci/djag073","DOIUrl":"10.1093/jnci/djag073","url":null,"abstract":"<p><strong>Background: </strong>While genome-wide association studies (GWAS) have identified hundreds of cancer-associated genetic variants, the specific biological contexts where these variants exert their effects remain largely unknown. We aimed to prioritize context-specific genetic risk mechanisms for 11 solid cancers at both genome-wide and single-variant resolutions.</p><p><strong>Methods: </strong>We integrated cancer GWAS summary statistics from European ancestry samples (avg. n cases = 47,856) with 1,473 context-specific annotations representing candidate cis-regulatory elements. For genome-wide analysis, we applied CT-FM, a method that jointly models heritability enrichments across annotations to select likely disease-relevant biological contexts. Following functionally informed fine-mapping to identify high-confidence (PIP ≥ 0.5) causal SNPs, we used CT-FM-SNP to identify relevant contexts for individual variants. A combined SNP-to-gene framework was applied to construct putative {regulatory SNP-context-gene-cancer} quadruplets.</p><p><strong>Results: </strong>Stratified LD score regression analysis identified 141 annotations showing significant heritability enrichment (FDR q ≤ 0.05). CT-FM prioritized four high-confidence (PIP ≥ 0.5) biological contexts mammary luminal epithelial cells for overall and estrogen receptor (ER)-positive breast cancer, a prostate cancer epithelial cell line (VCaP) for prostate cancer, and bulk tumor tissue contexts for colorectal and renal cancers. Variant-level analysis of hundreds of putatively causal SNPs aligned with these findings and identified additional high-confidence contexts for ER-negative breast, endometrial, lung, and bladder cancers. A total of 489 putative regulatory quadruplets were constructed, proposing specific molecular hypotheses underlying the observed GWAS signals.</p><p><strong>Conclusion: </strong>These findings advance our understanding of genetic susceptibility to different cancers. Future work in larger, more diverse GWAS, coupled with more comprehensive annotation atlases, is essential to expand upon and validate our results.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Semprini.","authors":"Chenxi Jiang, Philip S Rosenberg, Robert A Bednarczyk, Hyuna Sung","doi":"10.1093/jnci/djag117","DOIUrl":"https://doi.org/10.1093/jnci/djag117","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RE: State-level progress in reducing cervical cancer incidence among US young women between the pre- and post-human papillomavirus vaccination eras.","authors":"Jason Semprini","doi":"10.1093/jnci/djag116","DOIUrl":"https://doi.org/10.1093/jnci/djag116","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Ismayilov and Altundag.","authors":"Ruiyi Xu, Hui Wang","doi":"10.1093/jnci/djag106","DOIUrl":"https://doi.org/10.1093/jnci/djag106","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RE: An immunosuppressive tertiary lymphoid structure is associated with adverse prognosis in gastric-type endocervical adenocarcinoma.","authors":"Rashad Ismayilov, Ozden Altundag","doi":"10.1093/jnci/djag105","DOIUrl":"https://doi.org/10.1093/jnci/djag105","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast cancer mortality by age and race and/or ethnicity across counties in the United States, 2000-2019.","authors":"Jinani Jayasekera, Somy Hooshmand, Paula D Strassle, Jacob Schneider, George A Mensah, Laverne Mensah, Stephanie George, Yekaterina O Kelly, Mathew M Baumann, Zhuochen Li, Theresa A McHugh, Michael Celone, Dillon O Sylte, Wichada La Motte-Kerr, Kayleigh Bhangdia, Lisa M Force, Christopher J L Murray, Christian S Alvarez, Kelvin Choi, Ali H Mokdad, Laura Dwyer-Lindgren, Eliseo J Pérez-Stable","doi":"10.1093/jnci/djag103","DOIUrl":"https://doi.org/10.1093/jnci/djag103","url":null,"abstract":"<p><strong>Background: </strong>We evaluated county-level variations in racial and/or ethnic disparities in breast cancer mortality rates across the U.S. over a 20-year period.</p><p><strong>Methods: </strong>Validated small-area estimation models were used to calculate breast cancer mortality rates by age and race and/or ethnicity among females across all U.S counties from 2000 to 2019. The estimates were corrected for misreporting of race and/or ethnicity on death certificates and age-standardized to the 2010 U.S. Census.</p><p><strong>Results: </strong>Age-standardized national breast cancer mortality rates declined between 2000 to 2019, from 33.6 (95% Uncertainty Interval 33.4 to 33.9) to 24.8 (24.6 to 25.0) deaths per 100,000 females. However, there were variations in breast cancer mortality rates across racial and/or ethnic populations at the county level. For instance, 243 of 1,478 counties showed increasing breast cancer mortality rates from 2000 to 2019 among Latina females aged <50 years (absolute increase (median): 0.23 deaths per 100,000; maximum: 1.0). County-level patterns for American Indian/Alaska Native females aged 50 to 74 years showed increasing breast cancer mortality rates across 108 of 474 counties (median: 4.4 per 100,000; max: 17.5). The largest county-level increases were seen among American Indian/Alaska Native (184 of 474 counties; median: 15.2 per 100,000; max: 124.0) and Asian (589 of 667 counties; median: 14.1 per 100,000, max: 41.0) females aged ≥75 years.</p><p><strong>Conclusions: </strong>Despite a substantial decrease in overall breast cancer mortality rates across all female populations combined in the U.S., there were significant county-level variations in breast cancer mortality rates by race and/or ethnicity.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The benefit of adjuvant pertuzumab and trastuzumab according to estrogen receptor and HER2 expression: a Sub-analysis of the APHINITY trial.","authors":"Elisa Agostinetto, Gabriella Gentile, Faye Samy, Serena Di Cosimo, Philippe Aftimos, Noam Pondé, Daniel Eiger, Matteo Lambertini, David Cameron, Astrid Kiermaier, Andrew Bailey, Giuseppe Viale, Sherene Loi, Martine Piccart, Evandro de Azambuja","doi":"10.1093/jnci/djag095","DOIUrl":"https://doi.org/10.1093/jnci/djag095","url":null,"abstract":"<p><strong>Background: </strong>Responses to anti-human epidermal growth factor receptor 2 (HER2) therapy can vary based on estrogen receptor (ER) expression and HER2 gene amplification. This study assessed the magnitude of benefit by adding pertuzumab to trastuzumab and chemotherapy by ER and HER2 levels in the APHINITY trial.</p><p><strong>Methods: </strong>APHINITY (NCT01358877; BIG 4 to 11) was a randomized, double-blind, phase III trial comparing pertuzumab vs placebo added to adjuvant trastuzumab and chemotherapy in 4804 HER2-positive early breast cancer patients. The primary endpoint of this exploratory analysis was invasive disease-free survival (IDFS). Subgroup analyses used Cox models across four groups defined by HER2 FISH ratio and ER status, adjusted for treatment arm, chemotherapy regimen, and nodal status or protocol version. Tumors with FISH ratio <2 were excluded, leaving 4782 evaluable cases. HER2 FISH ratio was classified as low (2 ≤ ratio <5) or high (≥5), and ER expression by IHC as negative or positive using 1% and 10% cut-offs. IDFS, HER2 FISH ratio, and ER expression were also analyzed by intrinsic molecular subtype.</p><p><strong>Results: </strong>All subgroups benefited from pertuzumab, with the largest reduction in HER2 FISH-low/ER-positive tumors (HR 0.70, 95% CI 0.51 to 0.95). Other subgroups showed smaller benefits, with HER2 FISH-high/ER-negative tumors having the least numerical improvement (HR 0.85, 95% CI 0.59 to 1.25). No significant IDFS differences were observed between HER2-enriched and non-HER2-enriched tumors.</p><p><strong>Conclusions: </strong>Pertuzumab numerically improved IDFS in all subgroups, greatest in HER2 FISH-low/ER-positive tumors. These exploratory findings are hypothesis-generating and support prospective validation of biomarker-guided strategies.</p><p><strong>Trial registration: </strong>clinicaltrials.gov Identifier NCT01358877.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture improves cognitive function and neuropsychiatric symptoms in breast cancer survivors: a pilot randomized controlled trial.","authors":"Ding Quan Ng, Matthew Heshmatipour, Julia Trudeau, Apeksha Sridhar, Brock Pluimer, Olivia G G Drayson, Sayeh M Lavasani, Ritesh Parajuli, Sanghoon Lee, Anshu Agrawal, Munjal M Acharya, Charles L Limoli, Richard E Harris, Lifang Xie, Shaista Malik, Alexandre Chan","doi":"10.1093/jnci/djag096","DOIUrl":"https://doi.org/10.1093/jnci/djag096","url":null,"abstract":"<p><strong>Background: </strong>We conducted a randomized, double-blinded pilot trial to compare the impact of two electroacupuncture (EA) regimens on co-occurring neuropsychiatric symptoms among breast cancer survivors (BCS).</p><p><strong>Methods: </strong>BCS who self-reported cognitive impairment, fatigue, insomnia, or psychological distress were randomized (1:1) to receive ten weekly EA to target either neuropsychiatric-specific (nEA) or non-neuropsychiatric-specific (sEA) acupoints. Primary endpoints were the within-group pre-post effect sizes (Glass's Δ) in symptom severities, adjusted for multiple comparisons (p-adjusted). Outcomes were assessed using neurocognitive tests (CANTAB®), PROs (FACT-Cog, MFSI-SF, EORTC QLQ-C30), plasma biomarkers, and neuroimaging. Responders were defined by reliable change index (for objective cognition) or MCID (for PROs).</p><p><strong>Results: </strong>Thirty-five were recruited, with 30 (86%) completing all sessions. The mean (±SD) age was 58.2 (±12.2) years, and 86% reported co-occurring symptoms. Following treatment, the nEA group demonstrated significant improvements in attention (T3: Δ = 0.562, T4: Δ = 0.708, both p-adjusted < 0.05) and distress (T3: Δ = 0.764, T4: Δ = 0.711, both p-adjusted < 0.05). More responders were observed after nEA treatment for objective cognition (42.9% vs 12.5%) and distress (50% vs 37.5%). nEA-treated participants showed increased gray matter volume compared to sEA (p = 0.033), which positively correlated with better attention function (r = 0.69, p = 0.020). nEA-related improvements in memory and response speed were associated with reduced connectivity in the Default Mode Network (DMN-SFG, r=-0.93, p < 0.01) and increased connectivity in the Dorsal Attention Network (DAN-SMG, r = 0.86, p < 0.001), respectively. All adverse events were grade 2 or lower.</p><p><strong>Conclusions: </strong>EA targeting neuropsychiatric-specific acupoints suggests improvements in cognition and distress symptoms in BCS, warranting validation in larger, multicenter trials.</p><p><strong>Clinicaltrials.gov: </strong>NCT05283577.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RE: Electroacupuncture for quality of life during adjuvant chemotherapy in gastric cancer: a randomized trial.","authors":"Man Sun, Dan Zang, Jun Chen","doi":"10.1093/jnci/djag012","DOIUrl":"10.1093/jnci/djag012","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"757-758"},"PeriodicalIF":7.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer risks in the Lynch syndromes.","authors":"William D Foulkes, Aysel Ahadova","doi":"10.1093/jnci/djag029","DOIUrl":"10.1093/jnci/djag029","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"563-566"},"PeriodicalIF":7.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}