Cancer prevention research (Philadelphia, Pa.)最新文献

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Prediagnostic Serum Immune Marker Levels and Multiple Myeloma: A Prospective Longitudinal Study Using Samples from the Janus Serum Bank in Norway. 诊断前血清免疫标志物水平与多发性骨髓瘤:一项前瞻性纵向研究,使用来自挪威Janus血清库的样本。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-07-01 DOI: 10.1158/1940-6207.CAPR-24-0501
Simona Herdenberg, Carl Wibom, Esmeralda J M Krop, Hilde Langseth, Roel Vermeulen, Sophia Harlid, Wendy Yi-Ying Wu, Florentin Späth
{"title":"Prediagnostic Serum Immune Marker Levels and Multiple Myeloma: A Prospective Longitudinal Study Using Samples from the Janus Serum Bank in Norway.","authors":"Simona Herdenberg, Carl Wibom, Esmeralda J M Krop, Hilde Langseth, Roel Vermeulen, Sophia Harlid, Wendy Yi-Ying Wu, Florentin Späth","doi":"10.1158/1940-6207.CAPR-24-0501","DOIUrl":"10.1158/1940-6207.CAPR-24-0501","url":null,"abstract":"<p><p>Multiple myeloma is preceded by monoclonal gammopathy of undetermined significance (MGUS). Only a minority of patients with MGUS will develop multiple myeloma, but precise prediction of progression is impossible using routine clinical biomarkers. Changes in the levels of blood immune markers can help predict disease progression. Data remain inconsistent for some markers of interest such as monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1α), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), fractalkine, and transforming growth factor-alpha (TGF-α). We aimed to investigate the associations between the prediagnostic serum levels of these candidate biomarkers and future multiple myeloma risk, as well as to assess marker changes over time. We performed a nested case-control study using prospective samples from the Janus Serum Bank in Norway to investigate associations between multiple myeloma risk and prediagnostic serum levels of MCP-3, MIP-1α, FGF-2, VEGF, fractalkine, and TGF-α. The study included 293 future multiple myeloma cases with serum samples collected 20 years (median) before multiple myeloma diagnosis and 293 matched cancer-free controls. Patients with multiple myeloma had an additional prediagnostic sample collected up to 42 years before diagnosis to identify marker changes over time. Markers with >60% detection rate (MIP-1α, VEGF, and TGF-α) were included in the statistical analysis. We observed no statistically significant associations between multiple myeloma risk and serum levels of MIP-1α, VEGF, or TGF-α in samples collected 20 years before diagnosis. However, TGF-α levels decreased significantly closer to the diagnosis in patients with multiple myeloma (P < 0.001). The decrease in TGF-α levels may reflect subtle microenvironmental changes related to multiple myeloma progression.</p><p><strong>Prevention relevance: </strong>This study observed a decline in TGF-α serum levels closer to multiple myeloma diagnosis, which may aid in predicting multiple myeloma progression and early detection, although validation in other longitudinal cohorts is needed.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"383-391"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733473","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}
引用次数: 0
From Therapy to Cancer Prevention Using HRD Testing on Patients with High-grade Ovarian Cancer. HRD检测在高分级卵巢癌患者中的应用:从治疗到预防。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-07-01 DOI: 10.1158/1940-6207.CAPR-24-0474
Maria Grazia Tibiletti, Ileana Carnevali, Sofia Facchi, Valeria Pensotti, Giorgio Formenti, Nora Sahnane, Laura Libera, Susanna Ronchi, Sara Volorio, Marco Alessandro Pierotti, Stefano La Rosa, Fausto Sessa
{"title":"From Therapy to Cancer Prevention Using HRD Testing on Patients with High-grade Ovarian Cancer.","authors":"Maria Grazia Tibiletti, Ileana Carnevali, Sofia Facchi, Valeria Pensotti, Giorgio Formenti, Nora Sahnane, Laura Libera, Susanna Ronchi, Sara Volorio, Marco Alessandro Pierotti, Stefano La Rosa, Fausto Sessa","doi":"10.1158/1940-6207.CAPR-24-0474","DOIUrl":"10.1158/1940-6207.CAPR-24-0474","url":null,"abstract":"<p><p>Approximately half of high-grade ovarian cancers are characterized by genetic and epigenetic alterations in genes involved in homologous recombination repair (HRR), most commonly BRCA1 and BRCA2. HRR defects (HRD) identified by tests of genomic instability confer PARP inhibitor sensitivity in ovarian cancers. Commercial tests that combine tumor BRCA testing with a genomic instability score (HRD test) are available in clinical practice. We seek to determine the performance of three different HRD tests to improve therapy management and prevention of ovarian cancer. Tumor samples from 50 patients with high-grade ovarian cancers were investigated for tumoral BRCA status, genomic instability, and BRCA1 promoter methylation for treatment purposes. Patients with ovarian cancer that tested positive for BRCA variants and/or genomic instability defect were referred to the Cancer Genetics Service for germline testing. A positive HRD status was observed in 54% of cases, and pathogenic variants in BRCA genes were identified in 41% of cases presenting genomic instability. BRCA1 methylation assay revealed promoter hypermethylation in 20% of ovarian cancers that tested positive for HRD and negative for BRCA1/2 variants. Among 26 women referred to cancer genetic counseling, 10 carried germline variants in HRR genes. HRD status determined eligibility for PARP inhibitor treatment in all but two ovarian cancers. This study outlines that determining genomic instability helps identify inherited ovarian cancers. HRD testing, crucial for making high-grade ovarian cancer treatment choices, must be linked to an established path of cancer genetic counseling and management of individuals at high cancer risk.</p><p><strong>Prevention relevance: </strong>Genomic instability status (HRD testing), which is essential for making therapy choices, is useful to identify inherited ovarian cancers. Identifying these families with high cancer risk is critical for implementing targeted cancer prevention strategies.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"393-400"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054331","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}
引用次数: 0
Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention. 评估间歇性给药阿司匹林对结直肠癌的化学预防作用。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-06-02 DOI: 10.1158/1940-6207.CAPR-24-0168
Xiangzhu Zhu, Ruohui Chen, Reid M Ness, Rishi D Naik, Harvey J Murff, Heping Zhang, Yanfei Xu, Kelly A Benante, M Andrea Azcarate-Peril, Yinan Zheng, Jun Wang, Martha J Shrubsole, Timothy Su, Xinlei Mi, Masha Kocherginsky, Luz Maria Rodriguez, Gary Della'Zanna, Ellen Richmond, Lifang Hou, Seema A Khan, Qi Dai
{"title":"Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention.","authors":"Xiangzhu Zhu, Ruohui Chen, Reid M Ness, Rishi D Naik, Harvey J Murff, Heping Zhang, Yanfei Xu, Kelly A Benante, M Andrea Azcarate-Peril, Yinan Zheng, Jun Wang, Martha J Shrubsole, Timothy Su, Xinlei Mi, Masha Kocherginsky, Luz Maria Rodriguez, Gary Della'Zanna, Ellen Richmond, Lifang Hou, Seema A Khan, Qi Dai","doi":"10.1158/1940-6207.CAPR-24-0168","DOIUrl":"10.1158/1940-6207.CAPR-24-0168","url":null,"abstract":"<p><p>Aspirin reduces colorectal cancer risk but has a potential for adverse effects. Recent preclinical data suggest that intermittent dosing of aspirin may minimize adverse effects while maintaining efficacy. We conducted a three-arm double-blind randomized placebo-controlled phase II trial. The primary objective of the study was to test for the equivalency of two aspirin schedules, i.e., the effects of daily aspirin 325 mg/day continuously (cont-ASA) for 12 weeks or intermittently and 3 weeks on/3 weeks off on biomarkers related to colorectal carcinogenesis in rectal mucosa. A placebo group enabled the estimation of spontaneous biomarker variation. Eighty-one participants were randomized, of whom forty-five were evaluable. For the primary endpoint of decrease in the Ki-67:BCL2-associated X ratio, we could not establish equivalence for the two treatment regimens and also found no significant difference between them. For the secondary endpoint, cont-ASA treatment was significantly more effective in reducing the Ki-67:terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling ratio. Among exploratory endpoints, we found more reduction in epithelial COX-2 expression in the cont-ASA arm compared with the intermittent aspirin dosing arm. We did not observe significant differences in other secondary and exploratory endpoints. Intermittent aspirin dosing in 3-week cycles does not produce the same biologic effect as continuous dosing. Future studies should examine whether a 1-week on/1-week off schedule can maximize the efficacy and minimize the side effects. Prevention Relevance: In this three-arm double-blind randomized placebo-controlled phase II trial, we could not establish equivalence for daily aspirin 325 mg versus intermittent aspirin (3 weeks on/3 weeks off) on Ki-67:BCL2-associated X ratio. However, compared with intermittent aspirin administration, continuing aspirin was significantly more effective in reducing the Ki-67:terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling ratio and COX-2 in rectal mucosa.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"321-334"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544744","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}
引用次数: 0
Characteristics of the Newly Eligible Population under Two Recent Updates of Lung Cancer Screening Recommendations. 新近更新的两项肺癌筛查建议下新合格人群的特征
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-06-02 DOI: 10.1158/1940-6207.CAPR-24-0465
Yu Liu, Michael T Halpern, Robert J Volk, Ya-Chen Tina Shih
{"title":"Characteristics of the Newly Eligible Population under Two Recent Updates of Lung Cancer Screening Recommendations.","authors":"Yu Liu, Michael T Halpern, Robert J Volk, Ya-Chen Tina Shih","doi":"10.1158/1940-6207.CAPR-24-0465","DOIUrl":"10.1158/1940-6207.CAPR-24-0465","url":null,"abstract":"<p><p>The United States Preventive Services Task Force updated its lung cancer screening (LCS) recommendations in 2021, and the American Cancer Society (ACS) updated its LCS guidelines in 2023. Each update expanded screening eligibility criteria, thus increasing the total number of individuals eligible for LCS. However, it is not clear whether different population subgroups benefit equally from the recent updates of LCS recommendations in terms of becoming newly eligible. We identified 85,395 individuals who were between 50 and 80 years old, smoked cigarettes formerly or currently, and did not have a history of lung cancer from the Behavioral Risk Factor Surveillance System survey of 2022. We used descriptive analysis to illustrate the weighted proportions of the newly screening-eligible population among different subgroups. We also applied multivariable logistic regression models to estimate the ORs of being newly eligible for LCS under each LCS recommendation update in 2021 and 2023. For both LCS updates, individuals who were non-Hispanic White males and had chronic obstructive pulmonary disease were significantly more likely to become newly eligible for LCS. A significantly larger proportion of older-age individuals became newly eligible under the 2023 ACS guideline. Noticeably, both guideline updates substantially increased the population eligible for screening among males and older individuals, two groups experiencing the majority of lung cancer incidence and mortality. Results also indicate that the screening eligibility criteria updates did not increase the OR of being eligible among racial/ethnic minority and female subgroups. Prevention Relevance: This study examines the evolving LCS guidelines and their public health impact. Analyzing the 2021 United States Preventive Services Task Force and 2023 ACS updates, we show expanded eligibility but persistent disparities among sociodemographic groups. Our findings highlight the need for targeted interventions to improve screening uptake and promote equitable, inclusive prevention strategies.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"365-373"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035900","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}
引用次数: 0
Deriving a Mammogram-Based Risk Score from Screening Digital Breast Tomosynthesis for 5-Year Breast Cancer Risk Prediction. 基于乳房x光检查的数字乳房断层合成风险评分,用于5年乳腺癌风险预测。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-06-02 DOI: 10.1158/1940-6207.CAPR-24-0427
Shu Jiang, Debbie L Bennett, Graham A Colditz
{"title":"Deriving a Mammogram-Based Risk Score from Screening Digital Breast Tomosynthesis for 5-Year Breast Cancer Risk Prediction.","authors":"Shu Jiang, Debbie L Bennett, Graham A Colditz","doi":"10.1158/1940-6207.CAPR-24-0427","DOIUrl":"10.1158/1940-6207.CAPR-24-0427","url":null,"abstract":"<p><p>Screening digital breast tomosynthesis (DBT) aims to identify breast cancer early when treatment is most effective, leading to reduced mortality. In addition to early detection, the information contained within DBT images may also inform subsequent risk stratification and guide risk-reducing management. Using transfer learning, we refined a model in the Joanne Knight Breast Health Cohort at Washington University, a cohort of 5,066 women with DBT screening (mean age, 54.6), among whom 105 were diagnosed with breast cancer (26 ductal carcinoma in situ). We applied the model to external data from the Emory Breast Imaging Dataset, a cohort of 7,017 women free from cancer (mean age, 55.4), among whom 111 pathology-confirmed breast cancer cases were diagnosed more than 6 months after initial DBT (17 ductal carcinoma in situ). We obtained a 5-year AUC of 0.75 [95% confidence interval (CI), 0.73-0.78] in the internal validation. The model validated in external data gave an AUC of 0.72 (95% CI, 0.69-0.75). The AUC was unchanged when age and Breast Imaging-Reporting and Data System density were added to the model with synthetic DBT images. The model significantly outperforms the Tyrer-Cuzick model, with a 5-year AUC of 0.56 (95% CI, 0.54-0.58; P < 0.01). Our model extends risk prediction applications to synthetic DBT, provides 5-year risk estimates, and is readily calibrated to national risk strata for clinical translation and guideline-driven risk management. The model could be implemented within any digital mammography program. Prevention Relevance: We develop and externally validate a 5-year risk prediction model for breast cancer using synthetic DBT and demonstrate clinical utility by calibrating to the national risk strata as defined in breast cancer risk management guidelines.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"347-354"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607352","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}
引用次数: 0
Cancer Screening Progress and Noninvasive Screening Opportunities since the Onset of the COVID-19 Pandemic. 自2019冠状病毒病大流行以来,癌症筛查进展和无创筛查机会。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-06-02 DOI: 10.1158/1940-6207.CAPR-25-0007
John M Carethers
{"title":"Cancer Screening Progress and Noninvasive Screening Opportunities since the Onset of the COVID-19 Pandemic.","authors":"John M Carethers","doi":"10.1158/1940-6207.CAPR-25-0007","DOIUrl":"10.1158/1940-6207.CAPR-25-0007","url":null,"abstract":"<p><p>Cancer screening lowers morbidity and mortality from cancer and is cost-effective. The COVID-19 pandemic upended cancer screening utilization in 2020 with data showing a deficit in screened patients in 2020 and 2021 as compared with 2019, with return to 2019 baseline screening levels by December 2022. The cumulative shortfall in screenings, lasting nearly 3 years into the pandemic, is predicted by models to generate an incremental population cancer burden in the out-years of the models. Recovery of screening rates may vary based on the racial or ethnic population, and time will tell if there is an uneven burden of future cancers that worsen cancer incidence and mortality in those populations, some even after years of gains of reducing disparities for cancer screening. For some cancer screenings, particularly cervical and colorectal cancers, use of at-home noninvasive tests may increase screening participation overall across multiple populations and help mitigate some of the screening shortfalls from 2020 to 2022 by elevating numbers of the population screened. For colorectal cancer, new additional comparably sensitive or ease-of-use noninvasive screening tests are being added for utilization.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"18 6","pages":"313-319"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200877","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}
引用次数: 0
Lower Neighborhood-Level Socioeconomic Status Is Associated with Lower Colorectal Cancer Screening Uptake in the Southern Community Cohort Study. 在南部社区队列研究中,较低的社区社会经济地位与较低的结直肠癌筛查率有关。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-06-02 DOI: 10.1158/1940-6207.CAPR-24-0541
Lauren Giurini, Ronald E Gangnon, Amy Trentham-Dietz, Wei Zheng, Loren Lipworth, Harvey J Murff, Mark Steinwandel, Jennifer Weiss, Shaneda Warren Andersen
{"title":"Lower Neighborhood-Level Socioeconomic Status Is Associated with Lower Colorectal Cancer Screening Uptake in the Southern Community Cohort Study.","authors":"Lauren Giurini, Ronald E Gangnon, Amy Trentham-Dietz, Wei Zheng, Loren Lipworth, Harvey J Murff, Mark Steinwandel, Jennifer Weiss, Shaneda Warren Andersen","doi":"10.1158/1940-6207.CAPR-24-0541","DOIUrl":"10.1158/1940-6207.CAPR-24-0541","url":null,"abstract":"<p><p>Colorectal cancer is highly preventable with timely screening, but screening modalities are widely underused, especially among those of low individual-level socioeconomic status (SES). In addition to individual-level SES, neighborhood-level SES may also play a role in colorectal cancer screening completion through less geographic access to health care, transportation, and community knowledge of and support for screenings. We investigated the associations of neighborhood SES using a census tract-level measure of social and economic conditions with the uptake of colonoscopy and stool-based testing. We utilized data from the Southern Community Cohort Study, a large, prospective study of English-speaking adults ages 40 to 79 from the southeastern United States with 65% of participants identifying as non-Hispanic Black and 53% having annual household income <$15,000. Neighborhood SES was measured via a neighborhood deprivation index compiled from principal component analysis of 11 census-tract variables in the domains of education, employment, occupation, and poverty; screening was self-reported at the baseline interview (2002-2009) and follow-up interview (2008-2012). We found that participants residing in the lowest SES areas had lower odds of ever undergoing colonoscopy (ORQ5vsQ1 = 0.75; 95% confidence interval, 0.68-0.82) or stool-based colorectal cancer testing (ORQ5vsQ1 = 0.71; 95% confidence interval, 0.63-0.80) while adjusting for individual-level SES factors. Associations were consistent between neighborhood SES and screening in subgroups defined by race, sex, household income, insurance, or education (P > 0.20 for all interaction tests). Our findings suggest that barriers to screening exist at the neighborhood level and that residents of lower SES neighborhoods may experience more barriers to screening using colonoscopy and stool-based modalities. Prevention Relevance: This study presents evidence that persons living in lower SES neighborhoods use colorectal cancer screening modalities at lower rates. Screening is highly preventive of colorectal cancer, but it has limited benefit if it cannot be utilized. Addressing neighborhood-level barriers to screening may improve socioeconomic disparities in colorectal cancer.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"355-363"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665126","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}
引用次数: 0
Randomized Phase II Clinical Trial of Sulforaphane in Former Smokers at High Risk for Lung Cancer. 萝卜硫素在肺癌高风险戒烟者中的随机II期临床试验。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-06-02 DOI: 10.1158/1940-6207.CAPR-24-0386
Jian-Min Yuan, Thomas W Kensler, Sanja Dacic, Douglas J Hartman, Renwei Wang, Paula A Balogh, Pamela Sufka, Melissa A Turner, Kimberly Fuhrer, Lindsey Seigh, Yen Thi-Hai Pham, Jennifer Adams-Haduch, Giuseppe Valacchi, Shivendra V Singh, James G Herman, David O Wilson
{"title":"Randomized Phase II Clinical Trial of Sulforaphane in Former Smokers at High Risk for Lung Cancer.","authors":"Jian-Min Yuan, Thomas W Kensler, Sanja Dacic, Douglas J Hartman, Renwei Wang, Paula A Balogh, Pamela Sufka, Melissa A Turner, Kimberly Fuhrer, Lindsey Seigh, Yen Thi-Hai Pham, Jennifer Adams-Haduch, Giuseppe Valacchi, Shivendra V Singh, James G Herman, David O Wilson","doi":"10.1158/1940-6207.CAPR-24-0386","DOIUrl":"10.1158/1940-6207.CAPR-24-0386","url":null,"abstract":"<p><p>Experimental studies have shown that dietary isothiocyanates reduced cellular proliferative marker Ki-67 and increased apoptotic markers caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in animals, but human data are lacking. The present study was to assess whether sulforaphane would stop/reverse the progression of bronchial histopathology, reduce the Ki-67 index, and/or increase caspase-3 and TUNEL indices in humans. A randomized clinical trial (NCT03232138) was conducted in former smokers. Forty-three subjects were randomly assigned to the placebo or the treatment with a potential daily dose of 95 μmol sulforaphane for 12 months. The endpoints were the changes in histopathology scores and Ki-67, caspase-3, and TUNEL indices in post- versus pretreatment bronchial biopsies. Thirty-seven participants (17 in the sulforaphane and 20 in the placebo group) completed the study. Supplementation of sulforaphane did not show significant impact on bronchial histopathology but significantly reduced the Ki-67 index with a 20% decrease in the sulforaphane group and a 65% increase in the placebo (P = 0.014). The difference was even greater in high-density (3+) positive Ki-67, with a 44% decrease in the sulforaphane group compared with a 71% increase in the placebo (P = 0.004). Higher bioavailability of sulforaphane was correlated with greater reduction of the Ki-67 index (P for trend = 0.019). Sulforaphane treatment had no impact on the caspase-3 or TUNEL index in bronchial biopsies. No severe adverse event was observed in the study participants. The findings of oral sulforaphane that significantly reduced the Ki-67 index in bronchial tissue support further development as a potential chemopreventive agent against lung cancer development. Prevention Relevance: High intake of cruciferous vegetables and their sulforaphane is associated with lower incidence of lung cancer in humans and animal models. This clinical trial has demonstrated that oral supplementation of sulforaphane for 12 months significantly reduced the Ki-67 index, a potential surrogate endpoint of biomarkers for lung cancer risk.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"335-345"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560218","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}
引用次数: 0
Chronic Cigarette Smoke Exposure Masks Pathological Features of Helicobacter pylori Infection While Promoting Tumor Initiation. 慢性香烟烟雾暴露掩盖了幽门螺杆菌感染的病理特征,同时促进肿瘤的发生。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-05-01 DOI: 10.1158/1940-6207.CAPR-24-0378
Maeve T Morris, Benjamin C Duncan, M Blanca Piazuelo, I Mark Olfert, Xiaojiang Xu, Salik Hussain, Richard M Peek, Jonathan T Busada
{"title":"Chronic Cigarette Smoke Exposure Masks Pathological Features of Helicobacter pylori Infection While Promoting Tumor Initiation.","authors":"Maeve T Morris, Benjamin C Duncan, M Blanca Piazuelo, I Mark Olfert, Xiaojiang Xu, Salik Hussain, Richard M Peek, Jonathan T Busada","doi":"10.1158/1940-6207.CAPR-24-0378","DOIUrl":"10.1158/1940-6207.CAPR-24-0378","url":null,"abstract":"<p><p>Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Chronic infection by the bacterium Helicobacter pylori is the most prominent gastric cancer risk factor, but only 1% to 3% of infected individuals will develop gastric cancer. Cigarette smoking is another independent gastric cancer risk factor, and H. pylori-infected smokers are at a 2- to 11-fold increased risk of gastric cancer development, but the direct impacts of cigarette smoke (CS) on H. pylori pathogenesis remain unknown. In this study, male C57BL/6 mice were infected with H. pylori and began smoking within 1 week of infection. The mice were exposed to CS 5 days/week for 8 weeks. CS exposure had no notable impact on gross gastric morphology or inflammatory status compared with filtered-air (FA) exposed controls in mock-infected mice. However, CS exposure significantly blunted H. pylori-induced gastric inflammatory responses, reducing gastric atrophy and pyloric metaplasia development. Despite blunting these classic pathological features of H. pylori infection, CS exposures increased DNA damage within the gastric epithelial cells and accelerated H. pylori-induced dysplasia onset in the INS-GAS gastric cancer model. These data suggest that cigarette smoking may clinically silence classic clinical symptoms of H. pylori infection but enhance the accumulation of mutations and accelerate gastric cancer initiation. Prevention Relevance: These findings suggest that cigarette smoking suppresses pathophysiological hallmarks of H. pylori infection while accelerating gastric carcinogenesis. Therefore, smokers should receive screening for H. pylori infection to reduce gastric cancer risk. See related Spotlight, p. 257.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"271-281"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959785","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}
引用次数: 0
Use Patterns of Levonorgestrel-Releasing Intrauterine System among American Women. 美国妇女释放左炔诺孕酮宫内系统的使用模式。
Cancer prevention research (Philadelphia, Pa.) Pub Date : 2025-05-01 DOI: 10.1158/1940-6207.CAPR-24-0302
Paul G Yeh, Allen Haas, Charlotte C Sun, Karen H Lu, Larissa A Meyer, Iakovos Toumazis
{"title":"Use Patterns of Levonorgestrel-Releasing Intrauterine System among American Women.","authors":"Paul G Yeh, Allen Haas, Charlotte C Sun, Karen H Lu, Larissa A Meyer, Iakovos Toumazis","doi":"10.1158/1940-6207.CAPR-24-0302","DOIUrl":"10.1158/1940-6207.CAPR-24-0302","url":null,"abstract":"<p><p>Levonorgestrel-releasing intrauterine system (LNG-IUS) use is approved by the FDA for contraception and heavy menorrhagia. More importantly, it effectively treats endometrial hyperplasia, a precursor to endometrial cancer. Therefore, LNG-IUS use is associated with potential endometrial cancer risk reduction, but current use patterns in the United States are unknown. We analyzed LNG-IUS use prevalence among women ages 18 to 50 years using a weighted statistical analysis of the 2017 to 2019 National Survey of Family Growth. Summary statistics were stratified by race and ethnic group and known endometrial cancer sociodemographic and health risk factors and assessed statistically with bivariate Rao-Scott χ2 tests. A multivariable logistic regression model was developed to explore LNG-IUS use predictors. Current LNG-IUS use in the United States was 6.9% [95% confidence interval (CI), 5.9%-8.1%]. LNG-IUS use was lower in Hispanic women compared with White women [adjusted OR (AOR), 0.7; 95% CI, 0.5-1.0]. Compared with women with ≤high school education, LNG-IUS use was higher for women with ≥college degree (AOR, 2.0; 95% CI, 1.3-3.1). Parous (AOR, 2.6; 95% CI, 1.7-3.9) and insured (AOR, 1.7; 95% CI, 1.0-3.1) women had higher odds of LNG-IUS use, whereas women with diabetes (AOR, 0.3; 95% CI, 0.1-0.7) had lower odds of LNG-IUS use. No differences in LNG-IUS use were observed by endometrial cancer risk factors of women's body mass index, age of menarche, hypertension, and personal history of cancer. More research is needed to establish the potential benefits of LNG-IUS use on endometrial cancer, which will further highlight potential opportunities for population-level primary prevention to address the growing incidence of endometrial cancer. Prevention Relevance: This study describes the characteristics of American women using the LNG-IUS. Reproductive-age women (especially Hispanic, with lower education, nulliparous, uninsured, and with diabetes) have lower LNG-IUS use odds. These groups may benefit from LNG-IUS use for endometrial cancer primary prevention, conditioned that LNG-IUS use is proven effective in reducing endometrial cancer incidence.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"299-306"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392646","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}
引用次数: 0
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