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 = 47 856 cases) with 1473 context-specific annotations representing candidate cis-regulatory elements. For genome-wide analysis, we applied cell-type fine-mapping (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 causal single nucleotide polymorphisms (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 (false discovery rate, q ≤ 0.05). CT-FM prioritized 4 high-confidence biological contexts (posterior inclusion probability ≥  0.5): mammary luminal epithelial cells for overall and estrogen receptor (ER)-positive breast cancer, the VCaP (Vertebral-Cancer of the Prostate) epithelial cell line 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":"1836-1845"},"PeriodicalIF":7.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650368/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: TP53 Status as a Determinant of Pro- vs Anti-Tumorigenic Effects of Estrogen Receptor-Beta in Breast Cancer.","authors":"","doi":"10.1093/jnci/djag277","DOIUrl":"10.1093/jnci/djag277","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"1989-1990"},"PeriodicalIF":7.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The unfinished story of pregnancy-associated breast cancer.","authors":"Cyril Roussel-Simonin, Elie Rassy","doi":"10.1093/jnci/djag191","DOIUrl":"10.1093/jnci/djag191","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"1788-1790"},"PeriodicalIF":7.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591690","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 Yu, Wang, and Ge.","authors":"Florence Joly, Amélie Anota, Sylvie Chabaud, Claire Cropet, Eric Pujade-Lauraine, Jean-Emmanuel Kurtz, Isabelle Ray-Coquard","doi":"10.1093/jnci/djag213","DOIUrl":"10.1093/jnci/djag213","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"1985-1986"},"PeriodicalIF":7.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy history, recency of childbirth, and outcomes in young women with early-stage breast cancer.","authors":"Guilherme Nader-Marta, Yue Zheng, Shoshana M Rosenberg, Kate E Dibble, Erica L Mayer, Philip D Poorvu, Kathryn J Ruddy, Yaileen D Guzman-Arocho, Laura C Collins, Jeffrey Peppercorn, Lidia Schapira, Carmine Valenza, Virginia F Borges, Nabihah Tayob, Steven E Come, Ellen Warner, Kornelia Polyak, Eric P Winer, Ann H Partridge","doi":"10.1093/jnci/djag152","DOIUrl":"10.1093/jnci/djag152","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) diagnosed during pregnancy or postpartum often presents with aggressive features, potentially influenced by hormonal, immunological, and tissue remodeling changes. Studies have suggested that postpartum BC may be associated with worse outcomes, though most evidence is retrospective and constrained by methodological limitations. This study evaluated associations between pregnancy history, recency of childbirth, and long-term outcomes in a prospective cohort of young patients with early-stage BC.</p><p><strong>Patients and methods: </strong>Patients aged ≤40 years with stage I-III BC enrolled in the Young Women's Breast Cancer Study were categorized at diagnosis as nulligravid, nulliparous, pregnant, or parous (≤5 vs 5 to 10 years postpartum). Analyses were stratified by BC subtype (estrogen receptor-positive [ER+]/HER2-, HER2+, and triple-negative [TNBC]), with distant recurrence-free survival (DRFS) as the primary endpoint.</p><p><strong>Results: </strong>Among 859 patients, 257 (29.9%) were nulligravid, 50 (5.8%) nulliparous, 37 (4.3%) pregnant, and 515 (60.0%) parous. Pregnant patients had proportionally more TNBC, nodal involvement, T3/T4, and grade 3 tumors. After 11.1 years median follow-up, pregnancy or postpartum status was not independently associated with DRFS in multivariable models adjusted for age, tumor characteristics, and treatment, with consistent findings across ER+/HER2-, HER2+, and TNBC subtypes. Sensitivity analyses, including further categorization of postpartum diagnoses (<2 vs 2 to 5 years), yielded consistent results.</p><p><strong>Conclusions: </strong>Pregnancy history and recency of childbirth were not independently associated with long-term DRFS. Despite more aggressive features at diagnosis, patients diagnosed during or after pregnancy had comparable outcomes after adjustment, suggesting no adverse prognostic impact.</p><p><strong>Clinical trial registration: </strong>NCT01468246 (https://clinicaltrials.gov/study/NCT01468246? term=NCT01468246&rank=1).</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"1933-1941"},"PeriodicalIF":7.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972786","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":"Exercise slows biological aging in breast cancer survivors: secondary analysis of a randomized trial.","authors":"Daniel Carlin, Olivia Ott, Dorothy D Sears, Tim Ahles, Paula Desplats, Sheri J Hartman","doi":"10.1093/jnci/djag296","DOIUrl":"https://doi.org/10.1093/jnci/djag296","url":null,"abstract":"<p><strong>Background: </strong>Cancer and its treatments are associated with accelerated biological aging and cognitive impairment among breast cancer survivors. DNA methylation-based epigenetic clocks provide measures of biological aging that predict morbidity and mortality, yet little is known about whether these aging trajectories can be modified by lifestyle intervention. This secondary analysis of a subset of participants in a randomized controlled trial examined the impact of a 12-month exercise intervention on markers of epigenetic aging among breast cancer survivors.</p><p><strong>Methods: </strong>Sedentary breast cancer survivors within 5 years of diagnosis were randomized to a remotely delivered exercise intervention or a contact-matched health & wellness condition. Whole blood samples and cognitive assessments were obtained at baseline, 6, and 12 months. Epigenetic ages and differential methylation were calculated from normalized data obtained from the Methylation Screening Array.</p><p><strong>Results: </strong>A subsample of 124 participants with complete data was analyzed. The Exercise arm showed slower epigenetic aging than the Health & Wellness arm over the 12-month study, according to GrimAge2 (P = .02) and DNAmFitAge (P = .002) clocks. Changes in epigenetic aging were significantly correlated with alterations in attention and self-reported cognition, with faster epigenetic aging associated with greater cognitive decline. Furthermore, genome-wide analysis of the blood epigenome identified differentially methylated sites, some mapping to genes enriched for BDNF (brain-derived neurotrophic factor) signaling pathways.</p><p><strong>Conclusion: </strong>A 12-month exercise intervention was associated with slower epigenetic aging among breast cancer survivors. These findings suggest that biological aging may represent a modifiable mechanism through which exercise supports cognitive health in cancer survivorship.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04049695.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080982","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":"Effectiveness of an exercise intervention on cognition in breast cancer survivors: a randomized controlled trial.","authors":"Sheri J Hartman, Lucy Y Shao, Rong W Zablocki, Loki Natarajan, Tim Ahles, Barton W Palmer, Dorothy D Sears, Rowena M Tam, Victoria Mac, Lindsay Dillon, Chang Yan, Barbara A Parker","doi":"10.1093/jnci/djag295","DOIUrl":"https://doi.org/10.1093/jnci/djag295","url":null,"abstract":"<p><strong>Background: </strong>Cognitive problems are common after breast cancer, yet few randomized controlled trials have evaluated interventions to address them. This study tested whether a 12-month exercise intervention improved cognition in breast cancer survivors.</p><p><strong>Methods: </strong>Breast cancer survivors (n = 253) were randomized to an exercise arm with a remotely delivered intervention or a Health & Wellness arm receiving calls on healthy aging topics at the same frequency. The 6-month intervention (primary end-point) was followed by a 6-month maintenance phase (secondary end-point). At baseline, 3, 6, and 12 months, participants wore an accelerometer and completed the PROMIS Cognitive Abilities Questionnaire, the NIH Toolbox Digit symbol test (Processing Speed), and a neurocognitive battery assessing memory, executive function, and attention. Linear mixed models compared outcomes between arms.</p><p><strong>Results: </strong>The Exercise arm had greater increases in moderate to vigorous physical activity (18 minutes/day baseline, 23.5 minutes/day 12 months) than the Health & Wellness arm (15 minutes/day baseline, 15.5 minutes/day 12 months) at all follow-ups (P-values < .01). No significant between-group effects were observed for primary outcomes of self-reported cognition or processing speed at 6 or 12 months (P-values > .05). However, for secondary outcomes, the Exercise arm had greater improvements than the Health & Wellness arm in attention (6 months: b = 0.14, P = 0.03; 12 months: b = 0.21, P=.002), and memory (6 months: b = 0.18, P < .01).</p><p><strong>Conclusion: </strong>A remotely delivered Exercise intervention was not superior to a Health & Wellness intervention for self-reported cognition or processing speed. However, secondary outcomes suggest sustained improvements in attention and short-term benefits in memory. Exercise warrants further investigation as a strategy to support cognitive health in breast cancer survivors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04049695.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080876","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: Electro-acupuncture for quality of life during adjuvant chemotherapy in gastric cancer: a randomized trial.","authors":"Yang Yu, HangQi Meng, ChenBen Zhang","doi":"10.1093/jnci/djag333","DOIUrl":"https://doi.org/10.1093/jnci/djag333","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081019","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 Yu, Meng, and Zhang.","authors":"Rui Zhou, Yan-Juan Zhu, Jun J Mao, Hai-Bo Zhang","doi":"10.1093/jnci/djag334","DOIUrl":"https://doi.org/10.1093/jnci/djag334","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081009","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":"Helping patients make better choices by relabeling pattern 3 prostate disease as noncancerous.","authors":"Andrew J Vickers","doi":"10.1093/jnci/djag274","DOIUrl":"https://doi.org/10.1093/jnci/djag274","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074750","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}