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

{"title":"Systemic Inflammation and the Inflammatory Context of the Colonic Microenvironment Are Improved by Urolithin A.","authors":"Marmar R Moussa, Nuoxi Fan, John Birk, Anthony A Provatas, Pratik Mehta, Yuichiro Hatano, Ock K Chun, Manije Darooghegi Mofrad, Ali Lotfi, Alexander Aksenov, Vinicius N Motta, Maryam Zenali, Haleh Vaziri, James J Grady, Masako Nakanishi, Daniel W Rosenberg","doi":"10.1158/1940-6207.CAPR-24-0383","DOIUrl":"10.1158/1940-6207.CAPR-24-0383","url":null,"abstract":"<p><p>Diet affects cancer risk, and plant-derived polyphenols exhibit cancer-preventive properties. Walnuts are an exceptional source of polyphenolic ellagitannins, converted into urolithins by gut microflora. This clinical study examines the impact of urolithin metabolism on inflammatory markers in blood and colon polyp tissue. We evaluate the effects of walnut consumption on urinary urolithins, serum inflammatory markers, and immune cell markers in polyp tissues obtained from 39 subjects. Together with detailed food frequency data, we perform integrated computational analysis of metabolomic data combined with serum inflammatory markers and spatial imaging of polyp tissues using imaging mass cytometry. LC/MS-MS analyses of urine and fecal samples identify a widely divergent capacity to form nine urolithin metabolites in this patient population. Subjects with higher urolithin A formation exhibit lower levels of several key serologic inflammatory markers, including C-peptide, soluble form of intracellular adhesion molecule 1, sIL-6R, ghrelin, TRAIL, sVEGFR2, platelet-derived growth factor (PDGF), and MCP-2, alterations that are more pronounced in obese individuals for soluble form of intracellular adhesion molecule 1, epithelial neutrophil-activating peptide 78, leptin, glucagon-like peptide 1, and macrophage inflammatory protein 1δ. There is a significant increase in levels of peptide YY associated with urolithin A formation, whereas TNFα levels show an opposite trend, recapitulated in an in vitro system with ionomycin/phorbol 12-myristate 13-acetate-stimulated peripheral blood mononuclear cells (PBMC). Spatial imaging of colon polyp tissues shows altered cell cluster patterns, including a significant reduction of vimentin and CD163 expression associated with urolithin A. The ability to form urolithin A is linked to inflammation, warranting further studies to understand the role of urolithins in cancer prevention. Prevention Relevance: We evaluate cancer-protective effects of walnuts via formation of microbe-derived urolithin A, substantiating their functional benefits on serum inflammatory markers and immunologic composition of polyps in normal/obese subjects. Our approach incorporates personalized nutrition within the context of colonic health, providing the rationale for dietary inclusion of walnut ellagitannins for cancer prevention.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"235-250"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494940","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":"Editors' Selections from Relevant Scientific Publications.","authors":"","doi":"10.1158/1940-6207.CAPR-18-3-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-18-3-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"18 3","pages":"109"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538100","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":"Ursolic Acid as a Protective Agent against UVB-Induced Metabolic and Epigenetic Alterations in Human Skin Keratinocytes: An Omics-Based Study.","authors":"Shanyi Li, Zixin Li, Hsiao-Chen Dina Kuo, Ah-Ng Kong","doi":"10.1158/1940-6207.CAPR-24-0441","DOIUrl":"10.1158/1940-6207.CAPR-24-0441","url":null,"abstract":"<p><p>This study aimed to assess how ursolic acid (UA) can protect human skin keratinocytes from damage caused by UVB radiation. Utilizing an omics-based approach, we characterized the features of photodamage and investigated the potential of UA to reverse HaCaT cell subpopulation injury caused by UVB radiation. The most significant changes in metabolite levels after UA treatment were in pathways associated with phosphatidylcholine biosynthesis and arginine and proline metabolism. Treatment with UA can reverse the levels of certain metabolites, including creatinine, creatine phosphate, and succinic acid. Pathways activated by UA treatment in UVB-irradiated HaCaT cells were associated with several biological processes, including the positive regulation of protein modification process, cell division, and enzyme-linked receptor protein signaling pathway. Treatment with UA demonstrates the capability to mitigate the effects of UVB radiation on specific genes, including S100 calcium-binding protein A9 and IL6 receptor. DNA/CpG methylation indicates that UA can partially reverse some of the alterations in the UVB-induced CpG methylome. Utilizing integrated RNA sequencing and methylation sequencing data, starburst plots illustrate the correlation between mRNA expression and CpG methylation status. UA potentially influences the metabolic pathway of glycerophospholipid metabolism by modulating the expression of several key enzymes, including phospholipase A2 group IIA and lipin 2. Altogether, these results indicate that UVB radiation induces metabolic reprogramming, epigenetic changes, and transcriptomic shifts. Meanwhile, UA demonstrates the capacity to inhibit or reduce the severity of these alterations, which may underlie its potential protective role against skin damage caused by UVB exposure. Prevention Relevance: Our research indicates that UA has the potential to mitigate or lessen the impact of UVB radiation, which is known to cause metabolic reprogramming, epigenetic alterations, and transcriptomic changes. These effects could be responsible for UA's possible protective function against skin damage induced by UVB exposure.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"135-144"},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883718","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":"Association between Antibiotic Use and Subsequent Risk of Breast Cancer: A Nationwide Retrospective Cohort Study in South Korea.","authors":"Jaeyi Hong, Sun Jae Park, Young Jun Park, Seogsong Jeong, Seulggie Choi, Jooyoung Chang, Hye Jun Kim, Jihun Song, Ahryoung Ko, Su Gyeong Kim, Minjung Han, Yoosun Cho, Ji Soo Kim, Yun Hwan Oh, Joung Sik Son, Sang Min Park","doi":"10.1158/1940-6207.CAPR-24-0154","DOIUrl":"10.1158/1940-6207.CAPR-24-0154","url":null,"abstract":"<p><p>Several studies have revealed a possible association between antibiotic use and breast cancer in the Western population of women. However, its association with the Asian population remains unclear. Data utilized in this nationwide population-based retrospective cohort study were obtained from the Korean National Health Insurance Service database. The study population consisted of 4,097,812 women who were followed up from January 1, 2007, to December 31, 2019. Cox proportional hazards regression was utilized to calculate adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the risk of breast cancer according to cumulative days of antibiotic use and the number of antibiotic classes used. It was discovered that women who used antibiotics for more than 365 days had a higher risk of breast cancer (aHR, 1.15; 95% CI, 1.09-1.21) in comparison with those who did not use antibiotics. In addition, an association was found among women who used five or more classes of antibiotics, showing a higher risk of breast cancer (aHR, 1.11; 95% CI, 1.05-1.17) compared with nonusers. Furthermore, compared with antibiotic nonusers, only users of cephalosporins (aHR, 1.09; 95% CI, 1.02-1.17) and lincosamides (aHR, 1.70; 95% CI, 1.20-2.42) had a higher risk of breast cancer. These findings support epidemiologic evidence that long-term use of antibiotics may be associated with a higher risk of breast cancer. This underscores the need for further studies to address the potential for residual confounding, confirm causation, and elucidate the underlying mechanisms. Prevention Relevance: This study found a probable duration-dependent association between antibiotic prescriptions and breast cancer risk. The findings indicate that long-term antibiotic use could be associated with an increased risk of breast cancer and highlight the need for further research to confirm causality and mechanisms.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"125-133"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796668","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":"Nicotine Metabolite Ratio in People with HIV Who Smoke Cigarettes Receiving Pharmacologic and Behavioral Cessation Therapy.","authors":"Jonathan Shuter, Olivia A Davis, Chris deFilippi, Robert H Christenson, Lan Li, Wendy Potts, Seth Himelhoch","doi":"10.1158/1940-6207.CAPR-24-0449","DOIUrl":"10.1158/1940-6207.CAPR-24-0449","url":null,"abstract":"<p><p>People with human immunodeficiency virus (HIV; PWH) smoke cigarettes at triple the rate of the general population in the United States. Efforts to increase quit rates in this group have met with limited success. The nicotine metabolite ratio (NMR) has shown promise as a phenotypic marker that may be useful in selecting the most appropriate cessation treatments for people who smoke cigarettes. We completed a randomized controlled trial of individual intensive counseling and/or varenicline treatment for PWH in the Baltimore area who smoke cigarettes, and we measured serum 3' hydroxycotinine and cotinine at baseline and calculated the ratio of these two values, i.e., the NMR, for each participant. Herein, we present summary statistics and measures of association, or lack thereof, of NMR values with a variety of behavioral parameters and clinical outcomes related to tobacco use and tobacco treatment. The NMR was calculated for 155 PWH who were currently using tobacco cigarettes. The mean age was 52.9 years, 62.3% male, 91.0% Black, and they smoked a mean of 10.6 cigarettes/day. The mean NMR was 0.43, similar to that reported from other PWH cohorts. We did not find any significant correlation between NMR and cigarettes/day, nicotine dependence, temptation to smoke, or nicotine withdrawal symptoms. We did not find that lower NMR was predictive of successful cessation, nor was it associated with varenicline intolerance in those who received varenicline. Prevention Relevance: People with HIV suffer disproportionately from lung, head and neck, and other tobacco-related cancers as a consequence of high smoking rates. There is an urgent need to mitigate this harm, and the use of the NMR to personalize tobacco treatment is an area of active interest.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"111-115"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883715","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":"A Novel Sensitivity Maximization at a Given Specificity Method for Binary Classifications.","authors":"Seyyed Mahmood Ghasemi, Chunhui Gu, Johannes F Fahrmann, Samir Hanash, Kim-Anh Do, James P Long, Ehsan Irajizad","doi":"10.1158/1940-6207.CAPR-24-0236","DOIUrl":"10.1158/1940-6207.CAPR-24-0236","url":null,"abstract":"<p><p>In the cancer early detection field, logistic regression (LR) is a frequently used approach to establish a combination rule that differentiates cancer from noncancer. However, the application of LR relies on a maximum likelihood approach, which may not yield optimal combination rules for maximizing sensitivity at a clinically desirable specificity and vice versa. In this article, we have developed an improved regression framework, sensitivity maximization at a given specificity (SMAGS), for binary classification that finds the linear decision rule, yielding the maximum sensitivity for a given specificity or the maximum specificity for a given sensitivity. We additionally expand the framework for feature selection that satisfies sensitivity and specificity maximizations. We compare our SMAGS method with normal LR using two synthetic datasets and reported data for colorectal cancer from the 2018 CancerSEEK study. In the colorectal cancer CancerSEEK dataset, we report 14% improvement in sensitivity at 98.5% specificity (0.31 vs. 0.57; P value <0.05). The SMAGS method provides an alternative to LR for modeling combination rules for biomarkers and early detection applications. Prevention Relevance: This study introduces a new machine learning methodology that identifies the optimal features and combination rules to maximize sensitivity at a fixed specificity, making it applicable to many existing biomarker prevention studies.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"117-123"},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775312","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":"Editors' Selections from Relevant Scientific Publications.","authors":"","doi":"10.1158/1940-6207.CAPR-18-2-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-18-2-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"18 2","pages":"55"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082235","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":"Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women's Health Initiative.","authors":"Prasoona Karra, Sheetal Hardikar, Maci Winn, Garnet L Anderson, Benjamin Haaland, Aladdin H Shadyab, Marian L Neuhouser, Rebecca A Seguin-Fowler, Cynthia A Thomson, Mace Coday, Jean Wactawski-Wende, Marcia L Stefanick, Xiaochen Zhang, Ting-Yuan David Cheng, Shama Karanth, Yangbo Sun, Nazmus Saquib, Margaret S Pichardo, Su Yon Jung, Fred K Tabung, Scott A Summers, William L Holland, Thunder Jalili, Marc J Gunter, Mary C Playdon","doi":"10.1158/1940-6207.CAPR-24-0082","DOIUrl":"10.1158/1940-6207.CAPR-24-0082","url":null,"abstract":"<p><p>Body mass index (BMI) may misclassify obesity-related cancer (ORC) risk, as metabolic dysfunction can occur across BMI levels. We hypothesized that metabolic dysfunction at any BMI increases ORC risk compared with normal BMI without metabolic dysfunction. Postmenopausal women (n = 20,593) in the Women's Health Initiative with baseline metabolic dysfunction biomarkers [blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), and high-sensitive C-reactive protein (hs-CRP)] were included. Metabolic phenotype (metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy overweight/obese, and metabolically unhealthy overweight/obese) was classified using four definitions of metabolic dysfunction: (i) Wildman criteria, (ii) National Cholesterol Education Program Adult Treatment Panel III, (iii) HOMA-IR, and (iv) hs-CRP. Multivariable Cox proportional hazards regression, with death as a competing risk, was used to assess the association between metabolic phenotype and ORC risk. After a median (IQR) follow-up duration of 21 (IQR, 15-22) years, 2,367 women developed an ORC. The risk of any ORC was elevated among metabolically unhealthy normal weight (HR = 1.12, 95% CI, 0.90-1.39), metabolically healthy overweight/obese (HR = 1.15, 95% CI, 1.00-1.32), and metabolically unhealthy overweight/obese (HR = 1.35, 95% CI, 1.18-1.54) individuals compared with metabolically healthy normal weight individuals using Wildman criteria. The results were similar using Adult Treatment Panel III criteria, hs-CRP alone, or HOMA-IR alone to define metabolic phenotype. Individuals with overweight or obesity with or without metabolic dysfunction were at higher risk of ORCs compared with metabolically healthy normal weight individuals. The magnitude of risk was greater among those with metabolic dysfunction, although the CIs of each category overlapped. Prevention Relevance: Recognizing metabolic dysfunction as a significant risk factor for ORCs underscores the importance of preventive measures targeting metabolic health improvement across all BMI categories.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"63-72"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633122","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":"Calculating Future 10-Year Breast Cancer Risks in Risk-Adapted Surveillance: A Method Comparison and Application in Clinical Practice.","authors":"Silke Zachariae, Anne S Quante, Marion Kiechle, Kerstin Rhiem, Tanja N Fehm, Jörg-Gunther Schröder, Judit Horvath, Elena Leinert, Nicola Dikow, Joelle Ronez, Mirjam Schönfeld, Marion T van Mackelenbergh, Ulrich A Schatz, Cornelia Meisel, Bahriye Aktas, Dennis Witt, Yasmin Mehraein, Bernhard H F Weber, Christine Solbach, Dorothee Speiser, Juliane Hoyer, Gesine Faigle-Krehl, Christiane D Much, Alma-Verena Müller-Rausch, Pablo Villavicencio-Lorini, Maggie Banys-Paluchowski, Daniel Pieh, Rita K Schmutzler, Christine Fischer, Christoph Engel","doi":"10.1158/1940-6207.CAPR-24-0328","DOIUrl":"10.1158/1940-6207.CAPR-24-0328","url":null,"abstract":"<p><p>The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) has successfully implemented risk-adapted breast cancer surveillance for women at high breast cancer risk in Germany. Women with a family history of breast and ovarian cancer but without pathogenic germline variants in recognized breast cancer risk genes are recommended annual breast imaging if their predicted 10-year breast cancer risk is 5% or higher, using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) breast cancer risk model, as outlined in the current GC-HBOC guideline. However, women who initially do not meet this risk threshold may do so later, even if there is no new cancer in their family. To determine when this threshold is crossed, one could annually repeat BOADICEA calculations using an aging pedigree: the \"prediction by aging pedigree\" (AP) approach. Alternatively, we propose a simplified and more practical \"'conditional probability\" (CP) approach, which calculates future risks based on the initial BOADICEA assessment. Using data from 6,661 women registered with GC-HBOC, both methods were compared. Initially, 74% of women, ages 30 to 48 years, had a 10-year breast cancer risk below 5%, but 53% exceeded this threshold at an older age based on the AP approach. Among the women with an initial risk below the threshold, the CP approach revealed that 99% of women exceeded the 5% threshold at the same or an earlier age compared with the AP approach (88% of cases were within the same year or 1 year earlier). The CP approach has been implemented as a user-friendly web application. Prevention Relevance: The German Consortium for Hereditary Breast Cancer recommends annual breast imaging for women if their 10-year breast cancer risk is 5% or higher. Women who initially do not meet this risk threshold may do so later. We propose a simple method to determine future risks based on initial risk assessments.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"85-92"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689869","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":"Roles of Necroptosis, Apoptosis, and Inflammation in Colorectal Carcinogenesis: A Longitudinal Human Study.","authors":"Timothy Su, Xiangzhu Zhu, Yong Li, Chang Yu, Xinqing Deng, Eugene Shubin, Lifang Hou, Jing Zhao, Lei Fan, Heping Zhang, Harvey J Murff, Reid M Ness, Martha J Shrubsole, Qi Dai","doi":"10.1158/1940-6207.CAPR-24-0094","DOIUrl":"10.1158/1940-6207.CAPR-24-0094","url":null,"abstract":"<p><p>Necroptosis triggers an inflammatory cascade associated with antimicrobial defense. No prospective human study has yet explored the role of necroptosis in colorectal cancer development. We conducted quantitative analysis of biomarkers for necroptosis [transient receptor potential cation channel subfamily M member 7 (TRPM7) and phosphorylated mixed lineage kinase domain-like protein], inflammation [cyclooxygenase-2 (COX-2)], apoptosis [BCL2-associated X (BAX) and terminal deoxynucleotidyl transferase dUTP nick end labeling], and cell proliferation (Ki67). This was done using tissue microarray biospecimens from the Cooperative Human Tissue Network and rectal biopsies from a longitudinal study within the Personalized Prevention of Colorectal Cancer Trial. In the human colorectal adenoma-carcinoma sequence, we observed an inverse expression trend between BAX and TRPM7; TRPM7 decreased from normal mucosa to small and large adenomas but significantly increased in early colorectal cancer stages (Ptrend = 0.004). It maintained high levels through all cancer stages. An increased COX-2 intensity in the epithelium was noted during tumorigenesis (Ptrend = 0.02) and was significantly associated with an elevated risk of metachronous polyps (odds ratio = 3.04; 95% confidence interval, 1.07-8.61; Ptrend = 0.02). The combined composite index scores of TRPM7 and COX-2 were strongly linked to 6- to 47-fold increased risks for metachronous adenoma/serrated polyps, whereas combined scores of phosphorylated mixed lineage kinase domain-like protein or TRPM7 with BAX were associated with an 11.5- or 13.3-fold elevated risk for metachronous serrated polyps. In conclusion, our findings suggest that COX-2 expression within normal-looking colorectal mucosa is significantly associated with an increased risk of metachronous colorectal polyp. Furthermore, our results propose the hypothesis that synergistic interactions among necroptosis, inflammation, and apoptosis could play a pivotal role in human colorectal tumorigenesis. Prevention Relevance: Our findings suggest that COX-2 expression and combined scores of COX-2, TRPM7, and BAX hold promise for predicting the risk of metachronous polyps and could potentially serve as a tool for assessing the effectiveness of chemopreventive agents in preventing colorectal cancer during intervention trials.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"93-103"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787841","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}