Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology最新文献

{"title":"Association of Low Serum Vitamin B12 Concentration with Colorectal Cancer Risk and All-Cause Mortality: A Global Multi-Institutional Retrospective Cohort Study.","authors":"Yuan-Tsung Tseng, Kow-Tong Chen, Pei-Chen Lee, Liang-Yi Wang, Weir-Sen Lin, Yu-Hwei Tseng, Chung-Yi Li","doi":"10.1158/1055-9965.EPI-26-0761","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-26-0761","url":null,"abstract":"<p><strong>Background: </strong>The association between vitamin B12 deficiency and colorectal cancer (CRC) risk remains uncertain. We evaluated the association between low serum vitamin B12 concentration (<200 pg/mL) and CRC incidence and all-cause mortality, using a midrange reference group (400-600 pg/mL).</p><p><strong>Methods: </strong>In this retrospective propensity score-matched cohort study, adults with serum B12 measurements between 2006 and 2020 were identified from the TriNetX Global Collaborative Network. Patients with any neoplasm diagnosis within 5 years before the index date (first B12 measurement) were excluded. Patients with B12 <200 pg/mL were matched 1:1 to those with 400-600 pg/mL and followed for up to 10 years. Time-stratified, landmark, subgroup, E-value, and outcome-control analyses were performed.</p><p><strong>Results: </strong>After matching, 184,126 pairs were included. Low serum B12 was associated with higher CRC risk (HR 1.16; 95% CI, 1.09-1.23) and all-cause mortality (HR 1.16; 95% CI, 1.14-1.18). The CRC association persisted at the 2-year landmark (HR 1.16; 95% CI, 1.07-1.26) but attenuated at the 3-year (HR 1.07; 95% CI, 0.98-1.18) and 5-year (HR 1.12; 95% CI, 0.99-1.25) landmarks, whereas all-cause mortality remained elevated across all landmarks. The appendicitis negative control was null (HR 0.92; 95% CI, 0.84-1.02), whereas clavicle fracture was weakly positive (HR 1.08; 95% CI, 1.01-1.16).</p><p><strong>Conclusions: </strong>Low serum vitamin B12 was associated with higher all-cause mortality; its association with CRC was less robust at longer landmarks.</p><p><strong>Impact: </strong>The mortality association was more robust; the CRC finding requires prospective confirmation with serial B12 measurements.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946298","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":"Phenotypic and genotypic risk factors for uveal melanoma in a high ambient UV radiation environment.","authors":"Jane M Palmer, Catherine M Olsen, Matthew D'Mellow, Lindsay A McGrath, Sunil K Warrier, William J Glasson, Timothy Beckman, Huanwei Wang, Nirmala Pandeya, Matthew H Law, David C Whiteman, Nicholas K Hayward","doi":"10.1158/1055-9965.EPI-26-0734","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-26-0734","url":null,"abstract":"<p><strong>Background: </strong>Most evidence regarding risk factors for uveal melanoma (UM) derives from case-control studies prone to recall bias, and its rarity has limited prospective research. To address these gaps, we applied a population-based case-control design incorporating polygenic risk scores and Mendelian randomization to explore genetic and phenotypic determinants of UM risk.</p><p><strong>Methods: </strong>The study was conducted in Queensland, Australia. Incident UM cases diagnosed between 2011 and 2022 were recruited through specialist ocular oncology clinics. Controls were participants in the QSkin Sun and Health Study, a prospective cohort of 43,794 adults aged 40-69 at baseline (2010-2011). Demographic, phenotypic, and sun exposure factors were harmonized across studies. Polygenic risk scores were calculated for pigmentation traits and nevi characteristics using genome-wide association study datasets, and Mendelian randomization was used to assess potential causal relationships with UM risk.</p><p><strong>Results: </strong>Among 485 UM cases and 43,724 controls, several phenotypic traits were strongly associated with UM risk: male sex, blue or light eye color, inability to tan, freckling, and high nevus density. A family history of cutaneous melanoma and a personal history of keratinocyte cancer were also associated with higher risk. Polygenic risk score analyses confirmed significant associations for eye color and freckling. Mendelian randomization analyses supported causal relationships between lighter eye color, freckling propensity, reduced tanning ability and UM risk.</p><p><strong>Conclusions: </strong>These findings provide genetic evidence supporting a causal role for pigmentation-related traits in UM susceptibility.</p><p><strong>Impact: </strong>This evidence may help refine risk assessment and inform counselling for individuals with suspicious ocular lesions.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946334","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":"Associations Between Pre-diagnostic Plasma Metabolites and Ovarian Cancer: A Prospective Case-Cohort Analysis in the Cancer Prevention Study-3.","authors":"Brigitte A Pfluger, Matthew Masters, Nancy B Nguyen, Alpa V Patel, Lauren R Teras, Clara Bodelon, Victoria L Stevens, Shamim Shahi, Donghai Liang, Ying Wang","doi":"10.1158/1055-9965.EPI-26-0544","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-26-0544","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer remains a significant health concern among U.S. women, yet its underlying etiology is not fully understood. Untargeted metabolomics enables comprehensive profiling of small molecules that may provide insight into metabolic alterations associated with ovarian cancer risk.</p><p><strong>Methods: </strong>We conducted a case-cohort study within the Cancer Prevention Study-3, measuring pre-diagnostic plasma metabolites via untargeted metabolomics in 127 ovarian cancer cases and a randomly selected sub-cohort of 1,811 women, one of whom was later diagnosed with ovarian cancer. Median follow-up time was 2.4 years (IQR: 1.2-3.6) among ovarian cancer cases and 3.2 years (IQR: 2.5-5.2) in the sub-cohort. Metabolite associations with ovarian cancer risk were estimated using multivariable Prentice-weighted Cox models, and pathway enrichment analyses were performed. False discovery rate (FDR) correction was applied, considering FDR < 0.2 statistically significant.</p><p><strong>Results: </strong>Among 868 plasma metabolites analyzed, none showed statistically significant associations with ovarian cancer risk after FDR correction. In stratified analyses by menopausal status, five metabolites remained statistically significant after FDR correction among postmenopausal women only. Pathway enrichment analyses identified several lipid-related sub-pathways enriched among metabolites associated with ovarian cancer risk (FDR-adjusted p-value < 0.2), with the strongest positive enrichment observed for primary bile acid metabolism and the strongest negative enrichment for sphingomyelins.</p><p><strong>Conclusions: </strong>In this prospective metabolomics analysis, individual pre-diagnostic plasma metabolites were not associated with ovarian cancer risk, but lipid-related pathways and possible differences by menopausal status may warrant additional investigation.</p><p><strong>Impact: </strong>These findings contribute to the growing untargeted metabolomics literature on ovarian cancer.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922459","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":"Sunlight Exposure and Breast Cancer Risk: A Systematic Review and Meta-analysis.","authors":"Fausto Petrelli, Antonio Ghidini, Karen Borgonovo, Mara Ghilardi, Maria Chiara Parati, Loredana Burgoa, Lorenzo Dottorini, Mauro Rossitto, Giuseppina Dognini, Daniela Petrò, Veronica Lonati, Michele Ghidini, Gianluca Tomasello","doi":"10.1158/1055-9965.EPI-26-0666","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-26-0666","url":null,"abstract":"<p><p>Sunlight exposure may influence breast cancer risk through cutaneous vitamin D synthesis, circadian regulation, and immune modulation, yet prior meta-analyses were limited and did not examine hormone-receptor subtypes. In this systematic review and random-effects meta-analysis of 31 epidemiologic studies, higher sunlight exposure was associated with lower breast cancer incidence (pooled odds ratio 0.80; 95% confidence interval 0.74-0.86), with the strongest associations in case-control studies using personal exposure measures and weaker associations in cohorts relying on ambient-ultraviolet proxies. Protection was confined to estrogen-receptor-negative (0.71; 0.58-0.87) and triple-negative tumours (0.55; 0.37-0.81), with no association for estrogen-receptor-positive disease, and survival was improved for diagnoses in sunnier seasons (hazard ratio 0.84; 0.80-0.88), while a dose-response analysis indicated an 8% lower risk per 10 relative exposure units. Because the evidence is observational and subject to confounding and exposure misclassification, these hypothesis-generating findings nonetheless support further study of the light environment in breast cancer aetiology and prevention, balanced against skin-cancer risk.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922437","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":"Adaptation and Usability of a Lifestyle Cancer Prevention Screener for US Populations: A Mixed Methods Study.","authors":"Audrey A Goldbaum, Caitlin P Bailey, Amelia Willits-Smith, Jill Reedy, Kirsten A Herrick, Dora Romaguera, Alice Chaplin, Mar Nafría, Marissa M Shams-White","doi":"10.1158/1055-9965.EPI-26-0495","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-26-0495","url":null,"abstract":"<p><strong>Background: </strong>The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations provide evidence-based guidance on modifiable lifestyle factors associated with cancer risk. While a standardized scoring system exists to assess adherence at the population level, there is a lack of brief, culturally appropriate tools for assessing individual-level adherence in U.S.</p><p><strong>Settings: </strong>This study aimed to adapt and evaluate the usability of a WCRF/AICR Screener originally developed in Spain for use among U.S. adults.</p><p><strong>Methods: </strong>The screener was culturally adapted through expert review and included 17 items assessing anthropometrics, physical activity, diet, and breastfeeding. An iterative mixed-methods design was used, consisting of two rounds of online survey administration (round one: n=153; round two: n=151) followed by cognitive interviews (round one: n=5; round two: n=4). Quantitative usability was assessed using Likert-scale questions, and qualitative data were analyzed to evaluate comprehension and ease of use.</p><p><strong>Results: </strong>Across both rounds, over 90% of participants reported that the screener was easy to understand and would be acceptable for use in clinical or research settings. Cognitive interviews identified challenges related to dietary recall and interpretation of select items. Iterative refinements were tested to improve clarity, and the final screener demonstrated high acceptability.</p><p><strong>Conclusions: </strong>The adapted WCRF/AICR screener is a feasible, low-burden tool for assessing adherence to cancer prevention recommendations at the individual level in U.S. adults.</p><p><strong>Impact: </strong>With further validation, this instrument may support clinical counseling, risk communication, and intervention research targeting modifiable cancer risk factors.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922475","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":"Measurement of Treatment Adequacy Influences Racial Disparities Estimates in Endometrial Cancer Care.","authors":"Ashley S Felix, Caitlin E Meade, Simran A Kanal, Heidy N Medina, Allison M Quick, Tasleem J Padamsee, Jennifer A Sinnott","doi":"10.1158/1055-9965.EPI-26-0638","DOIUrl":"10.1158/1055-9965.EPI-26-0638","url":null,"abstract":"<p><strong>Background: </strong>Guideline-concordant treatment (GCT) is a key indicator of cancer care quality, yet most studies rely on cancer registry data, which incompletely capture treatment adequacy and vary in population composition. As a result, estimates of racial and ethnic disparities in GCT may differ depending on treatment measurement and populations represented in the data.</p><p><strong>Methods: </strong>We conducted analyses using Surveillance, Epidemiology, and End Results (SEER)-17, the National Cancer Database (NCDB), and SEER-Medicare to evaluate how treatment measurement and population composition influence disparities in guideline-concordant endometrial cancer treatment. GCT was defined according to National Comprehensive Cancer Network recommendations. Primary analyses used adequacy-based definitions incorporating treatment receipt, timing, amount, and duration, when available, while sensitivity analyses used receipt-based definitions based only on documented receipt. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between race/ethnicity and GCT within each data source. Additional sensitivity analyses evaluated influences of differences in underlying study populations.</p><p><strong>Results: </strong>Using adequacy-based definitions of GCT, Black patients had lower GCT odds than White patients (SEER OR=0.84, 95% CI=0.79-0.90; NCDB OR=0.75, 95% CI=0.73-0.77; SEER-Medicare OR=0.73, 95% CI=0.62-0.85). Within both NCDB and SEER-Medicare, adequacy-based definitions of GCT yielded larger racial and ethnic disparities than receipt-based definitions.</p><p><strong>Conclusions: </strong>The estimated magnitude of racial disparities in guideline-concordant endometrial cancer treatment are sensitive to treatment measurement and patient selection; sources capturing treatment adequacy show larger disparities.</p><p><strong>Impact: </strong>Measuring treatment adequacy provides a more comprehensive assessment of inequities in endometrial cancer care and may improve cancer disparities research, quality measurement, and policy.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Alcohol Use Among Adults with Cancer Participating in the ECOG-ACRIN EAQ171CD Tobacco Treatment Trial.","authors":"Angela Wangari Walter, JoRean D Sicks, Alexander Taurone, Sai Priyanka Mellacheruvu, Rachel L Rosen, Brett M Goshe, Ilana F Gareen, Benjamin A Herman, Autumn W Rasmussen, Alona Muzikansky, Susan Regan, Douglas E Levy, Michael A Thompson, Laura Malloy, Irina Gonzalez, Lucy Finkelstein-Fox, Nathan D Munson, Molly M Greenwade, David M King, Bharat Jenigiri, Brian L Burnette, Alyssa D Throckmorton, Martha S Tingen, Ruth C Carlos, Lynne I Wagner, Jamie S Ostroff, Elyse R Park","doi":"10.1158/1055-9965.EPI-26-0589","DOIUrl":"10.1158/1055-9965.EPI-26-0589","url":null,"abstract":"<p><strong>Background: </strong>Alcohol and tobacco use are known carcinogens. Treating alcohol and tobacco co-use can improve treatment and survivorship outcomes among patients diagnosed with cancer.</p><p><strong>Methods: </strong>We conducted a post hoc analysis of ECOG-ACRIN EAQ171CD trial participants within the NCI Community Oncology Research Program (NCORP), examining changes in alcohol use among adults receiving the virtual sustained treatment (VST) for tobacco use intervention versus enhanced usual care (EUC; Quitline referral). Multivariable logistic regression assessed changes in alcohol use disorder risk at 3 and 6 months using the AUDIT-C.</p><p><strong>Results: </strong>At baseline, participants (N = 305) were classified as no risk (31%), low/minimal risk (38%), moderate risk (23%), or high risk (8%) for alcohol use disorder. The mean age was 55.6 years, participants smoked for an average of 33 years, and 18% had alcohol-associated tumors. Participants randomized to EUC were more likely to shift to a lower alcohol risk category than those in the VST arm at 3 months (39% vs 27%) and 6 months (33% vs 27%). There was no significant difference in the odds of shifting to a lower risk category for VST vs EUC at 3 months (adjusted OR = 0.56, 95% CI 0.26-1.18, p = 0.125) or at 6 months (adjusted OR = 0.57, 95% CI 0.25-1.28, p = 0.172).</p><p><strong>Conclusions: </strong>Patients diagnosed with cancer and engaging in alcohol and tobacco co-use can achieve reductions in alcohol use and risk.</p><p><strong>Impact: </strong>Integrating tailored, co-use-focused strategies into cessation programs may improve changes in modifiable risk behaviors.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922457","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":"Serum soluble Fas levels and incidence of biliary tract cancer in a nested case-control study.","authors":"Yasushi Adachi, Masanori Nojima, Yingsong Lin, Yoshiharu Masaki, Ayako Murota, Yasushi Sasaki, Hiroshi Nakase, Kenji Wakai, Mitsuru Mori, Akiko Tamakoshi","doi":"10.1158/1055-9965.EPI-26-0782","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-26-0782","url":null,"abstract":"<p><strong>Background: </strong>Soluble Fas (sFas) plays multiple roles in tumorigenesis and cancer dissemination by avoiding apoptosis via connection to Fas ligand. We assessed associations of serum sFas levels with the incidence of extrahepatic biliary tract cancer (eBTC) in a prospective case-control study nested in the Japan Collaborative Cohort study.</p><p><strong>Methods: </strong>A baseline survey was conducted from 1988 using blood samples from 39,242 individuals (35% of 110,585). Patients diagnosed with eBTC, before the end of 1997, were regarded as cases. Odds ratios (ORs) for cancer incidence associated with sFas were estimated by conditional logistic regression.</p><p><strong>Results: </strong>This study included 73 cases and 215 controls. Participants with high sFas showed an elevated risk of cancer (P-trend = 0.01) and the third tertile of sFas showed a higher risk compared to the first tertile (OR 3.27, 95% confidence interval [CI] 1.37-7.80). In both gallbladder and extrahepatic bile duct cancers (n = 33 and 40, respectively), high sFas was associated with elevated risk (P-trend = 0.04 and 0.02, respectively). In women and the non-elderly, subjects in the highest tertiles showed higher cancer risk. Limiting subjects to those followed for over 2 years, high sFas was related to cancer risk (P-trend = 0.02) and the third tertile showed a higher risk compared to the first (OR 3.03, 95%CI 1.14-8.07).</p><p><strong>Conclusions: </strong>High serum sFas may be related to future risk of eBTC.</p><p><strong>Impact: </strong>These findings highlight the need for additional studies of this biomarker in large prospective cohorts and through integrated analysis involving other cohorts.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893310","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":"Modeled Sojourn Time and Sensitivity for Detecting Preclinical Cancers Retrospectively by a Multicancer Early Detection Test.","authors":"James Y Dai, E Georg Luebeck, William D Hazelton, Christina A Clarke, Earl Hubbell, Alpa V Patel","doi":"10.1158/1055-9965.EPI-25-1925","DOIUrl":"10.1158/1055-9965.EPI-25-1925","url":null,"abstract":"<p><strong>Background: </strong>Blood-based multicancer early detection tests have potential for clinical benefit, but key performance metrics for cancer screening, such as sojourn time and sensitivity of these tests for detecting preclinical disease, are not yet known.</p><p><strong>Methods: </strong>In a retrospective analysis of stored plasma samples in the American Cancer Society Cancer Prevention Study 3 (CPS3), GRAIL's MCED test was evaluated for detectability prior to cancer diagnosis. Classical state-transition models for cancer screening were modified to characterize the natural history of ctDNA-shedding cancers. The sensitivity estimand for detecting preclinical cancers by the MCED test was proposed in the context of retrospective testing, and a Bayesian likelihood method was developed to estimate preclinical detectable duration and sensitivity.</p><p><strong>Results: </strong>Analysis of CPS3 data showed that for the 12 prespecified cancers that represent two-thirds of cancer deaths in the United States, the test had 64% estimated overall sensitivity across all stages, and 43% sensitivity during an average 1.36-year preclinical detectable window before metastasis. Untestable assumptions on state transition and sensitivity are discussed, along with limitations related to using stored plasma samples.</p><p><strong>Conclusions: </strong>State-transition models were developed for retrospective analysis of plasma samples from the CPS3. Estimates for the length of the preclinical detectable window and the sensitivity at screening support annual MCED screening to intercept late-stage cancers.</p><p><strong>Impact: </strong>Retrospective analysis of plasma samples from the CPS3 supports the potential of GRAIL's MCED test to detect cancers early in the preclinical state. See related In the Spotlight, p. 1484.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1535-1544"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Association of Quantitative Background Parenchymal Enhancement with Breast Cancer Risk among Women with BRCA1/2 Pathogenic Variants.","authors":"Alex A Nguyen, Eric A Cohen, Sarah Ehsan, Walter C Mankowski, Bruno Barufaldi, Rhonda Gillette, Susan M Domchek, Despina Kontos, Anne Marie McCarthy","doi":"10.1158/1055-9965.EPI-25-1952","DOIUrl":"10.1158/1055-9965.EPI-25-1952","url":null,"abstract":"<p><strong>Background: </strong>Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) is a potential biomarker for breast cancer risk, but its utility among women with BRCA1/2 pathogenic variants (PV) is unclear.</p><p><strong>Methods: </strong>We investigated the longitudinal association of quantitative BPE measures with breast cancer risk among women with BRCA1/2 PVs. Measures included median BPE and the proportion of fibroglandular tissue (FGT) voxels with ≥20% enhancement (BPE20/FGT). The primary outcome was incident breast cancer diagnosed ≥6 months after MRI. Repeated measures proportional hazards models assessed associations of BPE with cancer, adjusting for age, menopausal status, volumetric breast density (VBD), body mass index (BMI), and BRCA type.</p><p><strong>Results: </strong>Among 385 women-39 of whom developed breast cancer-with 1,278 MRIs, the median age at first MRI was 36 (IQR 30-46) years. The BPE20/FGT ratio was associated with increased risk in both the smaller model (age and menopause adjusted, HR = 1.13, P < 0.005) and the larger model (adjusted for VBD, BMI, and BRCA1 vs. BRCA2, HR = 1.13, P < 0.005, both measures HR per 10 units). The association was stronger in axial MRIs in both models (smaller: HR = 1.26, P < 0.001; larger: HR = 1.34, P < 0.005). Median BPE showed similar results. In a subset of 165 women, a decrease in BPE was observed from the last measurement before oophorectomy to the first after oophorectomy (P < 0.04).</p><p><strong>Conclusions: </strong>In this study, higher BPE is associated with increased breast cancer risk in women with BRCA1/2 PVs, and BPE decreases after oophorectomy.</p><p><strong>Impact: </strong>Quantitative BPE may help better evaluate breast cancer risk for women with BRCA1/2 PVs, helping women balance the risks and benefits of risk-reducing interventions.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1637-1645"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148214080","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}