JNCI Journal of the National Cancer Institute最新文献

{"title":"Prophylactic antiviral therapy and all-cause mortality in cancer patients with hepatitis B e antigen-negative chronic hepatitis B virus infection receiving immunosuppressive therapy.","authors":"Sheng Nie, Lisha Cao, Licong Su, Shiyu Zhou, Yanqin Li, Ruixuan Chen, Fan Luo, Qi Gao, Yuxin Lin, Zhixin Guo, Xin Xu, Guobao Wang","doi":"10.1093/jnci/djaf032","DOIUrl":"https://doi.org/10.1093/jnci/djaf032","url":null,"abstract":"<p><strong>Background: </strong>The survival benefits of prophylactic antiviral therapy for cancer patients with HBeAg-negative chronic hepatitis B virus (HBV) infection who require immunosuppressive therapy (IST) remain unclear. The present study aims to evaluate the association of prophylactic antiviral therapy with all-cause and cause-specific mortality in cancer patients.</p><p><strong>Methods: </strong>This multicenter, retrospective cohort study included cancer patients with HBeAg-negative chronic HBV infection who received IST between January 2012 and December 2022. Patients were divided into groups with or without prophylactic antiviral therapy with nucleos(t)ide analogues. The primary outcome was all-cause mortality within one-year and secondary outcomes included cancer-related mortality, liver-related mortality, and HBV reactivation (HBVr). Confounding factors in patients who did and not receive antiviral prophylaxis were balanced by propensity score overlap weighting. The associations between prophylactic antiviral therapy and outcomes were assessed by Cox proportional hazards models.</p><p><strong>Results: </strong>Of the 3,677 cancer patients deemed eligible for inclusion, 1,541 (41.9%) initiated antiviral prophylaxis and 2,136 (58.1%) did not. After overlap weighting, prophylactic antiviral therapy was significantly associated with lower risks of all-cause mortality (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.70-0.96), cancer-related mortality (HR, 0.82; 95% CI, 0.69-0.97), and HBVr (HR, 0.49; 95%CI, 0.39-0.61) within one-year. Consistent results were found across various subgroups and multiple sensitivity analyses.</p><p><strong>Conclusions: </strong>Initiation of prophylactic antiviral therapy was associated with significant reductions in mortality and HBVr within one-year in cancer patients with HBeAg-negative chronic HBV infection who received IST in real-world clinical practice.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803397","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":"Following the American Cancer Society guideline for cancer survivors and obesity-related cancer survival.","authors":"Ying Wang, Christina C Newton, Marjorie L McCullough, Lauren R Teras, Clara Bodelon, Erika Rees-Punia, Caroline Y Um, Laura Makaroff, Alpa V Patel","doi":"10.1093/jnci/djaf051","DOIUrl":"https://doi.org/10.1093/jnci/djaf051","url":null,"abstract":"<p><strong>Background: </strong>In 2022, the American Cancer Society updated its guideline for cancer survivors. However, the impact of post-diagnosis adherence on mortality risk for those with obesity-related cancers remains unclear.</p><p><strong>Methods: </strong>This study followed nonsmoking participants from the Cancer Prevention Study-II Nutrition Cohort diagnosed with obesity-related cancers between 1992 and 2002 through 2020. Post-diagnosis adherence to ACS guidelines-body mass index (BMI), physical activity, diet, and alcohol consumption-was scored on a scale from 0 to 8. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Among 3,742 cancer survivors (mean age 67.6 years) with a median follow-up of 15.6 years, 2,430 deaths occurred. Survivors with a score of 6-8 had a 24% lower risk of all-cause mortality (HR, 0.76; 95% CI, 0.68-0.85), a 33% lower risk of cardiovascular disease mortality (HR, 0.67; 95% CI, 0.54-0.83), and a 21% lower risk of cancer-specific mortality (HR, 0.79; 95% CI, 0.64-0.97) compared to those with a score of 0-3. Higher BMI and physical activity scores were associated with lower all-cause mortality. Compared to survivors with a consistently low ACS guideline score (<5) both before and after diagnosis, those with a consistently high score (≥5) had lower all-cause and cardiovascular disease mortality. Additionally, survivors who improved their score from low to high had lower all-cause mortality.</p><p><strong>Conclusions: </strong>A lifestyle aligned with the ACS nutrition and physical activity guideline is associated with lower mortality risk among nonsmoking survivors of obesity-related cancers.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772657","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":"Obesity-specific improvement of lung cancer outcomes and immunotherapy efficacy with metformin.","authors":"Randall J Smith, Robert Zollo, Sukumar Kalvapudi, Yeshwanth Vedire, Akhil Goud Pachimatla, Cara Petrucci, Garrison Shaller, Deschana Washington, Vethanayagam Rr, Stephanie N Sass, Aravind Srinivasan, Eric Kannisto, Sawyer Bawek, Prantesh Jain, Spencer Rosario, Joseph Barbi, Sai Yendamuri","doi":"10.1093/jnci/djae295","DOIUrl":"10.1093/jnci/djae295","url":null,"abstract":"<p><strong>Background: </strong>Preclinical cancer studies ascribe promising anticancer properties to metformin. Yet, clinical findings vary, casting uncertainty on its therapeutic value for non-small cell lung cancer (NSCLC) patients. We hypothesized that metformin could benefit obese and overweight patients with NSCLC.</p><p><strong>Methods: </strong>We retrospectively analyzed 2 clinical cohorts and employed complementary mouse models to test our hypothesis. One cohort included NSCLC patients with overweight body mass index (≥25 kg/m2, n = 511) and nonoverweight body mass index (<25 kg/m2, n = 232) who underwent lobectomy, evaluating metformin's impact on clinical outcomes. Another cohort examined metformin's effect on progression-free survival after immune checkpoint inhibitors in overweight (n = 284) vs nonoverweight (n = 184) NSCLC patients. Metformin's effects on tumor progression, antitumor immunity, and immune checkpoint inhibitor response in obese and normal-weight mice were assessed with lung cancer models.</p><p><strong>Results: </strong>Metformin is associated with increased recurrence-free survival in overweight patients (hazard ratio [HR] = 0.47, 95% confidence interval [CI] = 0.24 to 0.94; P = .035) after lobectomy. It also corrected accelerated tumor growth in diet-induced obese mouse models in a lymphocyte-specific manner while reversing several mechanisms of immune suppression potentiated by obesity. Programmed cell death 1 blockade coupled with metformin was more effective at limiting tumor burden in obese mice and correlated with progression-free survival only in overweight patients on immunotherapy (HR = 0.60, 95% CI = 0.39 to 0.93; P = .024).</p><p><strong>Conclusions: </strong>Metformin may improve lung cancer-specific clinical outcomes in obese and overweight lung cancer patients and enhance immunotherapy efficacy in this growing population. This work identifies obesity as a potential predictive biomarker of metformin's anticancer and immunotherapy-enhancing properties in lung cancer while shedding light on the underlying immunological phenomena.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"673-684"},"PeriodicalIF":9.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667580","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":"State-level disparities in cervical cancer prevention and outcomes in the United States: a modeling study.","authors":"Fernando Alarid-Escudero, Valeria Gracia, Marina Wolf, Ran Zhao, Caleb W Easterly, Jane J Kim, Karen Canfell, Inge M C M de Kok, Ruanne V Barnabas, Shalini Kulasingam","doi":"10.1093/jnci/djae298","DOIUrl":"10.1093/jnci/djae298","url":null,"abstract":"<p><strong>Background: </strong>Despite human papillomavirus (HPV) vaccines' availability for over a decade, coverage across the United States varies. Although some states have tried to increase HPV vaccination coverage, most model-based analyses focus on national impacts. We evaluated hypothetical changes in HPV vaccination coverage at the national and state levels for California, New York, and Texas using a mathematical model.</p><p><strong>Methods: </strong>We developed a new mathematical model of HPV transmission and cervical cancer, creating national- and state-level models, incorporating country- and state-specific vaccination coverage and cervical cancer incidence and mortality. We quantified the national- and state-level impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 on cervical cancer outcomes and the time to elimination defined as less than 4 per 100 000 women.</p><p><strong>Results: </strong>Increasing vaccination coverage to 80% in Texas over 10 years could reduce cervical cancer incidence by 50.9% (95% credible interval [CrI] = 46.6%-56.1%) by 2100, from 1.58 (CrI = 1.19-2.09) to 0.78 (CrI = 0.57-1.02) per 100 000 women. Similarly, New York could see a 27.3% (CrI = 23.9%-31.5%) reduction from 1.43 (CrI = 0.93-2.07) to 1.04 (CrI = 0.66-1.53) per 100 000 women, and California a 24.4% (CrI = 20.0%-30.0%) reduction from 1.01 (CrI = 0.66-1.44) to 0.76 (CrI = 0.50-1.09) per 100 000 women. Achieving 80% coverage in 5 years will provide slightly larger and sooner reductions. If the vaccination coverage levels in 2019 continue, cervical cancer elimination could occur nationally by 2051 (CrI = 2034-2064), but state timelines may vary by decades.</p><p><strong>Conclusion: </strong>Targeting an HPV vaccination coverage of 80% by 2030 will disproportionately benefit states with low coverage and higher cervical cancer incidence. Geographically focused analyses can better inform priorities.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"737-746"},"PeriodicalIF":9.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681841","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":"BRCA1/2 germline sequencing in children and adolescents with cancer: it is the context that matters.","authors":"Catherine Goudie","doi":"10.1093/jnci/djae339","DOIUrl":"10.1093/jnci/djae339","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"580-582"},"PeriodicalIF":9.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028489","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":"Increased occurrence of malignancy before and after chemoradiation for anal squamous cell carcinoma: a multi-institutional analysis.","authors":"Ritesh Kumar, Chris L Hallemeier, Daniel T Chang, Shou-En Lu, Lara Hathout, Vasilis C Hristidis, Krishnan R Jethwa, J Richelcyn M Baclay, Veeraswamy Manne, Zakaria Chakrani, Michael G Haddock, Diego Augusto Santos Toesca, Erqi Liu Pollom, Abraham J Wu, Harigopal Sandhyavenu, Paul B Romesser, Salma K Jabbour","doi":"10.1093/jnci/djae309","DOIUrl":"10.1093/jnci/djae309","url":null,"abstract":"<p><strong>Background: </strong>Anal squamous cell carcinoma is a rare cancer with increased occurrence of multiple cancers before and after the anal squamous cell carcinoma diagnosis. However, there are limited data on this aspect. This multi-institutional analysis aimed to define the occurrence of malignancies before and after anal squamous cell carcinoma, time trends, and impact on survival and to identify prognostic factors.</p><p><strong>Methods: </strong>Initial primary malignancy was defined as a malignancy occurring before the anal squamous cell carcinoma. Second primary malignancy was defined as a distinct primary cancer that developed after anal squamous cell carcinoma diagnosis. Retrospective multi-institutional chart review was done. Progression-free survival (PFS), overall survival, and prognostic factors were evaluated.</p><p><strong>Results: </strong>A total of 647 patients with anal squamous cell carcinoma treated with curative intent were analyzed. Median age was 61.2 years with 72% as females. Of these, 150 (23.3%) patients had multiple malignancies with initial primary malignancy in 16% and second primary malignancy in 8%. Patients without prior cancer had better 5-year PFS (81.2% vs 67.2%, P = .011) and overall survival (81% vs 69%, P = .008) compared with those with prior cancer. Second primary malignancies had a statistically significant adverse impact on PFS (hazard ratio [HR] = 4.22) and overall survival (HR = 3.56). Females had better 5-year PFS (82% vs 70%, P = .016) as compared with males. The median time interval for developing anal squamous cell carcinoma (as second primary malignancy) after initial primary malignancy was 9.32 years.</p><p><strong>Conclusions: </strong>Anal squamous cell carcinoma patients have an increased risk of multiple malignancies. These patients who have prior cancers have inferior outcomes. Second primary malignancy is a poor prognostic factor in patients with anal cancer. Second primary malignancy can develop years after treatment of primary anal squamous cell carcinoma.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"772-780"},"PeriodicalIF":9.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769075","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: Effect of chemotherapy and surgery timing on mortality in upper and lower extremity osteosarcoma.","authors":"Liang Liu, Yan Xiao, ShengYao Liu, Zufeng Ye, Wei Liu","doi":"10.1093/jnci/djae332","DOIUrl":"10.1093/jnci/djae332","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"805-806"},"PeriodicalIF":9.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931733","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":"Utility of genomic testing in children, adolescents, and young adults with cancer.","authors":"Emily Debortoli, Ella McGahan, Tatiane Yanes, Jennifer Berkman, Noemi Fuentes-Bolanos, Vivienne Milch, Julia Steinberg, Aideen McInerney-Leo","doi":"10.1093/jnci/djae233","DOIUrl":"10.1093/jnci/djae233","url":null,"abstract":"<p><p>Genomic testing can inform the diagnosis and personalize management of cancers in children, adolescents, and young adults (CAYA). This scoping review explored the clinical utility and impact of genomic testing in general CAYA cancer cohorts. Relevant records published in English between 2017 and 2024 were identified by searching PubMed. 36 studies (32 original articles; 4 reviews) were identified on genomic testing in CAYA cancers, most of which were advanced cancers. Studies internationally reported that approximately 16%-18% of CAYAs with cancer carry an associated pathogenic germline variant where 40% are de novo, and can guide treatment (eg, DNA repair gene variants). Somatic variants, predominantly copy number or structural rearrangements, inform diagnosis in up to 95% of primary cancers. Between 18% and 69% of patients have a somatic variant with a matched therapy, but only one third receive the genomic-guided recommendation, predominantly due to declining patient condition. Few studies evaluated the impact of matched therapies on response and survival. Combining comprehensive DNA and RNA sequencing maximises sensitivity. Circulating tumour DNA was detected in most primary cancers and shows high concordance with tumour tissue. In conclusion, genomic testing of CAYA cancers is feasible, informs diagnoses and guides personalised care. Further research is needed on response to genomic-guided treatments.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"601-610"},"PeriodicalIF":9.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307796","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":"Implications of the initial Braidwood v. Becerra ruling for colorectal cancer outcomes: a modeling study.","authors":"Rosita Van Den Puttelaar, Kewei Sylvia Shi, Robert Smith, Jingxuan Zhao, Margaret Katana Ogongo, Matthias Harlass, Anne I Hahn, Ann G Zauber, K Robin Yabroff, Iris Lansdorp-Vogelaar","doi":"10.1093/jnci/djae244","DOIUrl":"10.1093/jnci/djae244","url":null,"abstract":"<p><p>The Affordable Care Act (ACA) eliminated patient cost-sharing for United States Preventive Service Task Force (USPSTF) recommended services. However, if the US Court of Appeals for the Fifth Circuit fully upheld a US District Court ruling in Braidwood Management v. Becerra, 666 F. Supp. 3d 613 (N.D. Tex 2023), cost-sharing for USPSTF recommendations made after ACA passage would have been reinstated for more than 150 million people. The case would have reinstated cost-sharing for colorectal cancer (CRC) screening for ages 45-49 years and for polyp removal during (diagnostic) colonoscopy across all ages. Using the MISCAN-Colon model, we simulated the potential impact on CRC outcomes, assuming early-onset CRC trends and lower screening participation. An 8-percentage-point decline in screening participation could increase CRC incidence by 5.1% and CRC mortality by 9.1%, with slightly lower costs due to increased cost-sharing. Larger decreases in screening participation can result in higher costs from increased incidence and delayed diagnoses.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"790-794"},"PeriodicalIF":9.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365304","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":"Childhood, adolescent, and young adulthood cancer risk in BRCA1 or BRCA2 pathogenic variant carriers.","authors":"Shuai Li, Laura Madanat-Harjuoja, Goska Leslie, Daniel R Barnes, Manjeet K Bolla, Joe Dennis, Michael T Parsons, Paraskevi Apostolou, Norbert Arnold, Kristin Bosse, Jackie Cook, Christoph Engel, D Gareth Evans, Florentia Fostira, Megan N Frone, Andrea Gehrig, Mark H Greene, Karl Hackmann, Eric Hahnen, Nadia Harbeck, Jan Hauke, Julia Hentschel, Judit Horvath, Louise Izatt, Marion Kiechle, Irene Konstantopoulou, Fiona Lalloo, Joanne Ngeow, Dieter Niederacher, Julia Ritter, Marta Santamariña, Rita K Schmutzler, Claire Searle, Christian Sutter, Marc Tischkowitz, Vishakha Tripathi, Ana Vega, Hannah Wallaschek, Shan Wang-Gohrke, Barbara Wappenschmidt, Bernhard H F Weber, Drakoulis Yannoukakos, Emily Zhao, Douglas F Easton, Antonis C Antoniou, Georgia Chenevix-Trench, Timothy R Rebbeck, Lisa R Diller","doi":"10.1093/jnci/djae306","DOIUrl":"10.1093/jnci/djae306","url":null,"abstract":"<p><strong>Background: </strong>Whether carriers of BRCA1 or BRCA2 pathogenic variants have increased risks of childhood, adolescent, and young adult cancers is controversial. We aimed to evaluate this risk and to inform clinical care of young BRCA1 and BRCA2 pathogenic variant carriers and genetic testing for childhood, adolescent, and young adult cancer patients.</p><p><strong>Methods: </strong>Using data from 47 117 individuals from 3086 BRCA1 or BRCA2 families, we conducted pedigree analysis to estimate relative risks (RRs) for cancers diagnosed before age 30 years.</p><p><strong>Results: </strong>Our data included 274 cancers diagnosed before age 30 years: 139 breast cancers, 10 ovarian cancers, and 125 nonbreast nonovarian cancers. Associations for breast cancer in young adulthood (aged 20-29 years) were found with relative risks of 11.4 (95% confidence interval [CI] = 5.5 to 23.7) and 5.2 (95% CI = 1.6 to 17.7) for BRCA1 and BRCA2 pathogenic variant carriers, respectively. No association was found for any other investigated childhood, adolescent, and young adult cancer or for all nonbreast nonovarian cancers combined; the relative risks were 0.4 (95% CI = 0.1 to 1.4) and 1.4 (95% CI = 0.7 to 3.0) in BRCA1 and BRCA2 pathogenic variant carriers, respectively.</p><p><strong>Conclusion: </strong>We found no evidence that BRCA1 and BRCA2 pathogenic variant carriers have an increased childhood, adolescent, and young adult cancer risk aside from breast cancer in women aged between 20 and 30 years. Our results, along with a critical evaluation of previous germline sequencing studies, suggest that the childhood and adolescent cancer risk conferred by BRCA1 and BRCA2 pathogenic variant would be low (ie, RR < 2) if it existed. Our findings do not support pathogenic variant testing for offspring of BRCA1 and BRCA2 pathogenic variant carriers at ages younger than 18 years or for conducting BRCA1 and BRCA2 pathogenic variant testing for childhood and adolescent cancer patients.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":"728-736"},"PeriodicalIF":9.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710347","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}