Cancer Prevention Research最新文献

{"title":"Construction and validation of a novel forecasting nomogram to the risk of colorectal adenomas: preventing colorectal cancer at its origin","authors":"Mao Li, Mingyu Cui, Xiaobin Zhou, Ying Song","doi":"10.1158/1940-6207.capr-24-0066","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-24-0066","url":null,"abstract":"Colorectal adenomas are responsible for the origin of most colorectal cancers (CRC). Early detection together with active intervention of colorectal adenomas plays a crucial role in the prevention of colorectal cancer. This study aimed to construct and validate a new nomogram for the forecasting of the risk of colorectal adenomas based on lifestyle risk factors that could offer potential benefits for CRC prevention. Colonoscopy reports, pathology reports, physical factors, family history, personal history of disease, diet, and lifestyle habits were collected from 1133 subjects who underwent complete colonoscopy. All subjects were divided into the training cohort (n = 792) and the validation cohort (n = 341). A nomogram predicting the risk of colorectal adenoma development was constructed using the training cohort and the C-index was calculated. The predictive accuracy and clinical applicability of the nomogram were verified in the validation cohort. The nomogram was constructed by 6 statistically significant variables selected from 18 health factors, including advanced age, male, smoking, drinking, pickles, and irregular defecation. The C-index of the training cohort was 0.778 and the C-index of the validation cohort was 0.754. The calibration curve and decision curve analysis (DCA) also confirmed that the model has good predictive ability and high profit. The nomogram constructed in this study was validated and can be applied to predicting the occurrence risk of colorectal adenoma. The model can guide the identification of patients with non-symptomatic colorectal adenomas and the recognition of high-risk individuals for whom a colonoscopy is advisable.","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"28 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Clonal Hematopoiesis Mutations and Canakinumab Treatment on Incidence of Solid Tumors in the CANTOS Randomized Clinical Trial","authors":"Janghee Woo, Tingting Zhai, Fang Yang, Huilei Xu, Margaret L. Healey, Denise P. Yates, Michael T. Beste, David P. Steensma","doi":"10.1158/1940-6207.capr-23-0342","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-23-0342","url":null,"abstract":"Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased pro-inflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS, NCT01327846) evaluated the neutralizing anti-IL-1β antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab vs those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL-1β blockade cooperating with CH mutations to modify the disease course.","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"12 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diet modulates the gut microbiome, metabolism, and mammary gland inflammation to influence breast cancer risk","authors":"Alana A. Arnone, Adam S. Wilson, David R. Soto-Pantoja, Katherine L. Cook","doi":"10.1158/1940-6207.capr-24-0055","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-24-0055","url":null,"abstract":"Several studies have indicated a strong link between obesity and the risk of breast cancer. Obesity decreases gut microbial biodiversity and modulates Bacteroidetes-to-Firmicutes proportional abundance, suggesting that increased energy-harvesting capacity from indigestible dietary fibers and elevated lipopolysaccharide bioavailability may promote inflammation. To address the limited evidence linking diet-mediated changes in the gut microbiota to breast cancer risk, we aimed to determine how diet affects the microbiome and breast cancer risk. Female 3-week-old BALB/c mice were fed six different diets (control, high-sugar, lard, coconut oil, lard+flaxseed oil, and lard+safflower oil) for 10 weeks. Fecal 16s sequencing was performed for each group. Diet shifted fecal microbiome populations and modulated mammary gland macrophage infiltration. Fecal conditioned media shifted macrophage polarity and inflammation. In our DMBA-induced breast cancer model, diet differentially modulated tumor and mammary gland metabolism. We demonstrated how dietary patterns change metabolic outcomes, and gut microbiota, which may contribute to breast tumor risk. Furthermore, we showed the influence of diet on metabolism, inflammation, and macrophage polarity. This study suggests that dietary-microbiome interactions are key mediators of breast cancer risk.","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"104 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the Hunt for the Missed Genetic Causes of Multiple Primary Tumors","authors":"Fiona Chan-Pak-Choon, William D. Foulkes","doi":"10.1158/1940-6207.capr-24-0115","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-24-0115","url":null,"abstract":"Improved cancer screening and treatment programs have led to an increased survivorship of patients with cancer, but consequently also to the rise in number of individuals with multiple primary tumors (MPT). Germline testing is the first approach investigating the cause of MPT, as a positive result provides a diagnosis and proper clinical management to the affected individual and their family. Negative or inconclusive genetic results could suggest non-genetic causes, but are negative genetic results truly negative? Herein, we discuss the potential sources of missed genetic causes and highlight the trove of knowledge MPT can provide. See related article by Borja et al., p. 209","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"10 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Economic Considerations for Implementing Tobacco Cessation Programs in Cancer Care Settings","authors":"Ramzi G. Salloum, Kimberly A. Shoenbill, Adam O. Goldstein","doi":"10.1158/1940-6207.capr-24-0122","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-24-0122","url":null,"abstract":"Increasingly, research demonstrates economic benefits of tobacco cessation in cancer care, as seen in a new study by Kypriotakis and colleagues of the MD Anderson cessation program, demonstrating median health care cost savings of $1,095 per patient over 3 months. While the cost-effectiveness of tobacco cessation programs from a hospital perspective is important, implementation decisions in a predominantly fee-for-service system, such as in the United States, too often insufficiently value this outcome. Economic barriers, stakeholder disincentives, and payment models all impact program implementation. Combining economic evaluation with implementation research, including assessment of return-on-investment, may enhance sustainability and inform decision-making in cancer care settings. See related article by Kypriotakis et al., p. 217","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"93 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stool protein mass spectrometry identifies biomarkers for the early detection of diffuse-type gastric cancer","authors":"Chi-Lee C. Ho, Michael B. Gilbert, Guillaume Urtecho, Hyoungjoo Lee, David A. Drew, Samuel J. Klempner, Jin S. Cho, Thomas J. Ryan, Naryan Rustgi, Hyuk Lee, Jeeyun Lee, Alexander Caraballo, Marina V. Magicheva-Gupta, Carmen Rios, Alice E. Shin, Yuen-Yi Tseng, Jeremy L. Davis, Daniel C. Chung, Andrew T. Chan, Harris H. Wang, Sandra Ryeom","doi":"10.1158/1940-6207.capr-23-0449","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-23-0449","url":null,"abstract":"There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of GC or individuals with hereditary diffuse GC (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of stool from a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells (known as TCON mice) identified differentially abundant proteins compared to littermate controls. Immunoblot assays validated a panel of proteins including actinin alpha 4 (ACTN4), N-acylsphingosine amidohydrolase 2 (ASAH2), dipeptidyl peptidase 4 (DPP4), and valosin-containing protein (VCP) as enriched in TCON stool compared to littermate control stool. Immunofluorescence analysis of these proteins in TCON stomach sections revealed increased protein expression as compared to littermate controls. Proteomic mass spectrometry of stool obtained from HDGC patients with CDH1 mutations identified increased expression of ASAH2, DPP4, VCP, lactotransferrin (LTF), and tropomyosin-2 (TPM2) relative to stool from healthy sex and age-matched donors. Chemical inhibition of ASAH2 using C6-urea ceramide was toxic to GC cell lines and patient derived-GC organoids. This toxicity was reversed by adding downstream products of the S1P synthesis pathway, suggesting a dependency on ASAH2 activity in GC. An exploratory analysis of the HDGC stool microbiome identified features which correlated with patient tumors. Here we provide evidence supporting the potential of analyzing stool biomarkers for the early detection of DGC.","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"1 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140802262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of H. pylori and gastric intestinal metaplasia in BRCA1 and BRCA2 carriers","authors":"Blake A. Niccum, Sarah Coughlin, Daniel Clay, Jordan Heiman, Kole H. Buckley, Michaela Dungan, Michael G. Daniel, Jose Ruiz, Kara N. Maxwell, Susan M. Domchek, Galen Leung, Nuzhat A. Ahmad, Gregory G. Ginsberg, Michael L. Kochman, Bryson W. Katona","doi":"10.1158/1940-6207.capr-24-0039","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-24-0039","url":null,"abstract":"BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer (GC), however the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of GC risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of GC in this population. 100 unselected BRCA1/2 carriers undergoing endoscopic ultrasound from 3/2022-3/2023 underwent concomitant upper endoscopy with non-targeted gastric antrum and body biopsies. The study population (70% women; mean age: 60.1) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no GCs were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to the general population, however identification of H. pylori or GIM may help inform future GC risk management strategies in BRCA1/2 carriers.","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"119 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Reach of a Patient Navigation Program for Follow-up Colonoscopy in a Large Federally Qualified Health Center","authors":"Priyanka Gautom, A. Gabriela Rosales, Amanda F. Petrik, Jamie H. Thompson, Matthew T. Slaughter, Leslie Mosso, Syed Akmal. Hussain, Ricardo Jimenez, Gloria D. Coronado","doi":"10.1158/1940-6207.capr-23-0498","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-23-0498","url":null,"abstract":"Patient navigation (PN) has been shown to improve participation in cancer screening, including colorectal cancer screening, and the Community Preventive Services Task Force now recommends the practice. Despite the effectiveness of PN programs, little is known about the number of contacts needed to successfully reach patients or about the demographic and healthcare utilization factors associated with reach. PRECISE was an individual randomized study of PN vs. usual care conducted as a partnership between two large health systems in the Pacific Northwest. The navigation program was a six topic-area telephonic program designed to support patients with an abnormal fecal test result to obtain a follow-up colonoscopy. We report the number of contact attempts needed to successfully reach navigated patients. We used logistic regression to report the demographic and healthcare utilization characteristics associated with patients allocated to PN who were successfully reached. We identified 1200 patients with an abnormal FIT result, among whom 970 were randomized into the study (45.7% were female, 17.5% were Spanish-speaking, mean age was 60.8). Of the 479 patients allocated to the PN intervention, 382 (79.7%) were reached within 18 call attempts and nearly all (n = 356; 93.2%) were reached within six contact attempts. Patient characteristics associated with reach were race, county of residence, and body mass index. Our findings can guide future efforts to optimize the reach of PN programs.","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline and Somatic Fumarate Hydratase Testing in Atypical Uterine Leiomyomata","authors":"Lindsay M. Kipnis, Katelyn M. Breen, Diane R. Koeller, Alison Schwartz Levine, Zelei Yang, Hyeji Jun, Nabihah Tayob, Samantha M. Stokes, Connor P. Hayes, Arezou A. Ghazani, Sarah J. Hill, Huma Q. Rana","doi":"10.1158/1940-6207.capr-23-0535","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-23-0535","url":null,"abstract":"Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown. To better understand FH germline PV prevalence and current patterns of genetic counseling and germline genetic testing, we undertook a retrospective review of atypical uterine leiomyomata cases at a single large center. We compared clinical characteristics between the FH PV, FH wild-type (WT), and unknown genetic testing cohorts. Of the 144 cases with atypical uterine leiomyomata with evaluable clinical data, only 49 (34%) had documented genetic test results, and 12 (8.3%) had a germline FH PV. There were 48 IHC-defined FH-deficient cases, of which 41 (85%) had FH testing and nine had a germline FH PV, representing 22% of the tested cohort and 18.8% of the FH-deficient cohort. Germline FH PVs were present in 8.3% of evaluable patients, representing 24.5% of the cohort that completed genetic testing. These data highlight the disconnect between pathology and genetic counseling, and help to refine risk estimates that can be used when counseling patients with atypical uterine leiomyomata. Prevention Relevance: Women diagnosed with fumarate hydratase (FH)-deficient uterine leiomyomata are at increased risk of renal cancer. This work suggests a more standardized pathology-genetic counseling referral pathway for these patients, and that research on underlying causes of FH-deficient uterine leiomyomata in the absence of germline FH pathogenic/likely pathogenic variants is needed.","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"1 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Fat Diet Induced PPARδ Promotes Self-renewal of Preleukemic Progenitors in Development of Acute Promyelocytic Leukemia","authors":"Hiroshi Y. Yamada, Chinthalapally V. Rao","doi":"10.1158/1940-6207.capr-23-0469","DOIUrl":"https://doi.org/10.1158/1940-6207.capr-23-0469","url":null,"abstract":"From risk association between acute promyelocytic leukemia (APL) and obese-overweight individuals, Mazzarella and colleagues hypothesized that a high-fat diet (HFD) promotes development of APL. Using mouse APL model (PML-RARα knock-in), the authors demonstrated that linoleic acid drives activation of PPARδ in hematopoietic progenitors, and that activation of PPARδ increases proliferation of progenitor cells with PML-RARA expression toward APL. Involvements of PPARδ on regulation of stem cell renewal and proliferation were shown in colorectal cancers earlier, but this study newly demonstrates in hematopoietic progenitors, while suggesting use of diet rich in linoleic acid with caution. See related article by Mazzarella et al., p. 59","PeriodicalId":9373,"journal":{"name":"Cancer Prevention Research","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139665717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}