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

{"title":"Alcohol Consumption Does not Modify the Polygenic Risk Score-Based Genetic Risk of Breast Cancer in Postmenopausal Women: Atherosclerosis Risk in Communities Study.","authors":"Minghui Zhang, Meng Ru, Jingning Zhang, Ziqiao Wang, Jiayun Lu, Kenneth R Butler, Nilanjan Chatterjee, David J Couper, Anna E Prizment, Mehrnoosh M Soori, Kala Visvanathan, Cynthia A Zahnow, Corinne E Joshu, Elizabeth A Platz","doi":"10.1158/1940-6207.CAPR-24-0208","DOIUrl":"10.1158/1940-6207.CAPR-24-0208","url":null,"abstract":"<p><p>High genetic risk and alcohol consumption ≥1 drink/day are associated with increased breast cancer risk. However, the interaction between alcohol and genetics on breast cancer risk is poorly understood, including in populations not enriched with daily drinkers. We prospectively studied 5,651 White and Black postmenopausal women in the Atherosclerosis Risk in Communities study. Alcohol intake was assessed by a food frequency questionnaire. The 313-SNP polygenic risk score (PRS) was calculated. Breast cancer cases were ascertained primarily by cancer registry linkage through 2015. Multivariable Cox regression was used to estimate HRs and 95% confidence intervals (CI) for the association of PRS and current ethanol intake with breast cancer, and their interaction. Of these individuals, 50.6% were current drinkers, and of them, 50.8% drank <1 drink/week and 12.8% drank >7 drinks/week. A higher PRS was associated with a higher breast cancer risk among White (HR1-SD, 1.48; 95% CI, 1.34-1.65) and Black (HR1-SD, 1.15; 95% CI, 0.96-1.38) women. Positive associations were not observed between current ethanol intake and breast cancer risk (White: HR13 g/week, 1.00; 95% CI, 0.98-1.03; Black: HR, 0.83; 95% CI, 0.69-1.00). Among both White and Black women, PRS generally seemed to be positively associated with risk in drinkers and nondrinkers. There was no evidence of a PRS-ethanol intake interaction among White or Black women. Patterns in Black women were similar when using an 89-SNP PRS developed among African ancestry women. In conclusion, in a prospective analysis of White and Black postmenopausal women in a study population not enriched with daily drinkers, our findings suggest that alcohol drinking does not modify the PRS-based genetic risk of breast cancer. Prevention Relevance: Although our findings suggest that alcohol drinking does not modify the PRS-based genetic risk of breast cancer among White and Black women with lower alcohol intake, nevertheless, women should consider limiting alcohol consumption as a general cancer prevention strategy, as indicated in dietary guidelines.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"73-83"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831120","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":"Biological Age Acceleration and Colonic Polyps in Persons under Age 50.","authors":"Chloe M Brown, Maria V Yow, Shria Kumar","doi":"10.1158/1940-6207.CAPR-24-0317","DOIUrl":"10.1158/1940-6207.CAPR-24-0317","url":null,"abstract":"<p><p>Epigenetic clocks can quantify DNA methylation by measuring the methylation levels at specific sites in the genome, which correlate with biological age (BA). Accelerated aging, where BA exceeds chronologic age, has been studied in relation to cancer development, but its utility in cancer prevention remains unclear. Accelerated aging holds promise as a tool to explain the increase in early-onset colorectal cancer (EOCRC). We investigate the association of accelerated aging and the presence of preneoplastic polyps (PNP) in the colon, defined as tubular adenomas and sessile serrated adenomas. In this study of persons under age 50 undergoing colonoscopy, we used peripheral blood samples to determine BA and age acceleration metrics. Age acceleration was determined by interrogating DNA methylation at specific CpG sites across the genome, which has been shown to correlate with age. We then conducted logistic regression analyses to evaluate the association between age acceleration and PNPs. In total, 51 patient samples were evaluated. We found that that the odds of harboring a PNP are 16% higher with 1 year of accelerated aging, as measured by GrimAge. However, the strongest risk factor for PNPs remained male sex. This represents one of the first studies to explore accelerated aging and PNP in patients under the age of 50. A risk-stratified approach to EOCRC screening would minimize unnecessary colonoscopies and minimize healthcare burden while addressing the increase in EOCRC. Our findings suggest that BA calculations with peripheral blood collections could be an important component of such a risk model. Prevention Relevance: Understanding the association of accelerated aging and colorectal PNPs presents an opportunity to develop a risk-stratified approach to colorectal cancer screening in young persons.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"57-62"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803618","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-18-1-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-18-1-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"18 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933779","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":"Phase II Clinical Chemoprevention Trial of Weekly Erlotinib before Bladder Cancer Surgery.","authors":"Tracy M Downs, Howard H Bailey, Taja Lozar, Natalie S Schmitz, Heather Green, Cameron O Scarlett, Thomas C Havighurst, Kyleigh Twaroski, Katina DeShong, Barbara Wollmer, Trinity J Bivalacqua, Daniel R Saltzstein, Neal Shore, KyungMann Kim, Wei Huang, William A Ricke, Lisa Barroilhet, Margaret House, Howard L Parnes, Edward Messing","doi":"10.1158/1940-6207.CAPR-24-0194","DOIUrl":"10.1158/1940-6207.CAPR-24-0194","url":null,"abstract":"<p><p>We performed a clinical trial in patients with non-muscle-invasive (NMI) urothelial cancer randomized (2:1) to the EGFR tyrosine kinase inhibitor erlotinib or placebo (either orally once weekly × 3 doses prior to scheduled surgery) to assess for a difference in EGFR phosphorylation in tumor-adjacent normal urothelium <24 hours post-study dose and tolerance of weekly erlotinib therapy. Thirty-seven volunteers (6 female/31 male; mean age 70; 35 White/2 non-White) with confirmed or suspected NMI urothelial cancer were enrolled into either erlotinib (n = 24; 900 mg-13, 600 mg-11) or placebo (n = 13). IHC assessment of phosphorylated and total EGFR in tumor-adjacent normal urothelium (20 erlotinib and 9 placebo subjects) or tumor (21 erlotinib and 11 placebo subjects) at study end showed no significant difference between those receiving erlotinib or placebo. This was also true for other assessed tissue biomarkers (phosphorylated ERK, ERK, E-cadherin, p53, and Ki67). Adverse events were more common, in a dose-related fashion, in participants receiving erlotinib, e.g., 38% experienced grade 1 with rare grade 2 diarrhea and skin toxicity versus 8% in placebo. Clinically insignificant but statistically significant (P = 0.001) elevations in serum total bilirubin and creatinine were observed in participants receiving erlotinib. Serum erlotinib and metabolite concentrations (OSI-420) confirmed compliance in all subjects receiving erlotinib and did not significantly differ between the 600 and 900 mg doses. Despite compelling preclinical and clinical data for targeted EGFR inhibition in bladder cancer prevention, these data do not support the use of weekly erlotinib therapy to prevent progression of NMI bladder cancer. Prevention Relevance: We evaluated the potential of erlotinib in preventing cancer by performing a randomized, double-blind, placebo-controlled trial of weekly erlotinib therapy in participants undergoing surgical removal of suspected noninvasive bladder neoplasia. Weekly erlotinib therapy was tolerated with common grade 1 to 2 toxicities but without evidence of beneficial effect upon urothelial tissue. See related Spotlight, p. 7.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"31-39"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074546","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":"What Is the Cost: Financial Toxicity and Screening Fatigue in Li-Fraumeni Syndrome.","authors":"Kaylee A Underkofler, Martha H Thomas, Sarah H Erickson, Alayna A Panzer, Kara S Fitzgibbon, Kari L Ring","doi":"10.1158/1940-6207.CAPR-24-0184","DOIUrl":"10.1158/1940-6207.CAPR-24-0184","url":null,"abstract":"<p><p>Patients with Li-Fraumeni syndrome (LFS) are recommended to follow a comprehensive surveillance protocol, but the demanding nature may limit adherence. We sought to identify barriers to adherence and to determine whether screening fatigue and financial hardship are contributors. A 39-item online survey was developed and distributed to patients presenting to a LFS clinic between 2017 and 2022. Of the 39 patients eligible, 20 responded to the survey (51%). Of the respondents, 75% reported they do not skip surveillance tests; however, this was not consistent when asked about specific tests, with only 65% and 40% up to date with colonoscopy and esophagogastroduodenoscopy, respectively. Hundred percent of those diagnosed within the last 5 years said they never skip tests, whereas only 50% of those diagnosed more than 5 years ago reported the same (P = 0.01). Barriers to adherence were reported by 85% and most commonly included finances (40%), time (25%), and difficulty scheduling (25%). Only 21% felt no financial stress, and 63% worried at least somewhat about their future financial situation because of LFS. Even with insurance, 65% felt their share of healthcare costs was too high. Adherence to rigorous cancer surveillance is imperfect and decreases over time among patients with LFS. Whereas number of tests was not a commonly cited barrier, time and difficulty scheduling were common and may contribute to screening fatigue. The degree of financial stress in the affluent population studied should raise even greater concern about financial strain in the LFS population in general. Prevention Relevance: Li-Fraumeni syndrome (LFS) essentially guarantees a cancer diagnosis in an affected individual's lifetime. Findings of this study reveal a difficulty for patients with LFS to adhere to recommended rigorous surveillance protocols and question how identified barriers can be broken down to reduce the morbidity and mortality of LFS.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"41-48"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633125","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":"Black Raspberry Modulates Cecal and Oral Microbiomes at the Early Stage of a Dibenzo[def,p]chrysene-Induced Murine Oral Cancer Model.","authors":"Jingcheng Zhao, Yuan-Wan Sun, Kun-Ming Chen, Cesar Aliaga, Jordan E Bisanz, Karam El-Bayoumy","doi":"10.1158/1940-6207.CAPR-24-0347","DOIUrl":"10.1158/1940-6207.CAPR-24-0347","url":null,"abstract":"<p><p>While tobacco smoking is a risk factor in the development of oral squamous cell carcinoma (OSCC), only a fraction of smokers develop the disease. Compelling evidence shows that microbial community composition is associated with carcinogenesis, suggesting that the microbiome may play a role in cancer development of smokers. We previously showed that black raspberry (BRB) protects against OSCC induced by the tobacco constituent dibenzo[def,p]chrysene (DBP) via alteration of genetic and epigenetic markers in a manner consistent with its cancer preventive activity. In the present study, we conducted a mouse experiment to investigate the effects of BRB and DBP individually and in combination on the oral and gut microbiota. DBP-induced DNA damage in the mouse oral cavity is an essential step for the development of OSCC in mice. 16S rRNA gene sequencing revealed that BRB significantly increased microbial diversity and shifted microbiome composition in the gut and oral cavity, whereas DBP had no significant effect. In both gut and oral microbiota, Akkermansia muciniphila was significantly reduced after BRB treatment; however, this was not consistent with pure culture in vitro assays suggesting that the impact of BRB on A. muciniphila may be mediated through indirect mechanisms including the host or other microbes. Indeed BRB, but not DBP, was found to modulate the growth kinetics of human gut microbes in vitro including lactic acid bacteria and Bacteroides spp. The results of the current study further emphasize the interplay of microbiome and environmental factors in the development and prevention of OSCC. Prevention Relevance: Our work clearly demonstrates the modulatory impact of BRB on both gut and oral microbiomes within a DBP-induced OSCC mouse model and paves the way for future research examining a causal role of BRB-microbiota interactions at different stages of disease progression.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"11-21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585076","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":"Passing the Torch forward: Moving beyond EGFR Inhibition in NMIBC Prevention.","authors":"Tsung-Che Wu, Chia-Chi Lin","doi":"10.1158/1940-6207.CAPR-24-0491","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-24-0491","url":null,"abstract":"<p><p>The study by Downs and colleagues targets patients with non-muscle-invasive bladder cancer (NMIBC) to explore secondary/tertiary cancer prevention strategies. Utilizing a \"window-of-opportunity\" design, erlotinib was evaluated for its effect on EGFR phosphorylation, although the unconventional dosing regimen failed to demonstrate efficacy. New opportunities in NMIBC prevention include targeting FGFR3 mutations with emerging FGFR inhibitors. A future trial design could focus on clinical outcomes such as tumor response and NMIBC recurrence while also evaluating FGFR3 inhibition in both tumor and adjacent normal bladder epithelia. See related article by Downs et al., p. 31.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"18 1","pages":"7-9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933782","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":"Automated Breast Density Assessment for Full-Field Digital Mammography and Digital Breast Tomosynthesis.","authors":"Shu Jiang, Debbie L Bennett, Simin Chen, Adetunji T Toriola, Graham A Colditz","doi":"10.1158/1940-6207.CAPR-24-0338","DOIUrl":"10.1158/1940-6207.CAPR-24-0338","url":null,"abstract":"<p><p>Mammographic density is a strong risk factor for breast cancer and is reported clinically as part of Breast Imaging Reporting and Data System (BI-RADS) results issued by radiologists. Automated assessment of density is needed that can be used for both full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) as both types of exams are acquired in standard clinical practice. We trained a deep learning model to automate the estimation of BI-RADS density from a prospective Washington University clinic-based cohort of 9,714 women, entering into the cohort in 2013 with follow-up through October 31, 2020. The cohort included 27% non-Hispanic Black women. The trained algorithm was assessed in an external validation cohort that included 18,360 women screened at Emory from January 1, 2013, and followed up through December 31, 2020, that included 42% non-Hispanic Black women. Our model-estimated BI-RADS density demonstrated substantial agreement with the density as assessed by radiologists. In the external validation, the agreement with radiologists for category B 81% and C 77% for FFDM and B 83% and C 74% for DBT shows important distinction for separation of women with dense breast. We obtained a Cohen's κ of 0.72 (95% confidence interval, 0.71-0.73) in FFDM and 0.71 (95% confidence interval, 0.69-0.73) in DBT. We provided a consistent and fully automated BI-RADS estimation for both FFDM and DBT using a deep learning model. The software can be easily implemented anywhere for clinical use and risk prediction. Prevention Relevance: The proposed model can reduce interobserver variability in BI-RADS density assessment, thereby providing more standard and consistent density assessment for use in decisions about supplemental screening and risk assessment.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"23-29"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514004","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":"Improved Uptake and Adherence to Risk-Reducing Medication with the Use of Low-Dose Tamoxifen in Patients at High Risk for Breast Cancer.","authors":"Lauren F Cornell, Christine L Klassen, Karthik Ghosh, Colleen Ball, Pooja Advani, Sandhya Pruthi","doi":"10.1158/1940-6207.CAPR-24-0324","DOIUrl":"10.1158/1940-6207.CAPR-24-0324","url":null,"abstract":"<p><p>Women at increased risk for breast cancer may benefit from taking risk-reducing medication (RRM) with tamoxifen (tam). Historical uptake of tam in women who qualify has been low. Recent studies have shown low-dose tam to have similar efficacy to standard dosing, with lower risk for adverse events. In this study, we aimed to evaluate uptake, adherence, and tolerability of low-dose tam in women at increased risk for breast cancer and those with ductal carcinoma in situ (DCIS). In this two-site prospective study, women who qualified for breast cancer RRM were offered participation and received consultation with a breast specialist for discussion of RRM rationale, benefits, side effects, and risks. Patients received baseline and 1-year follow-up surveys. A total of 41 patients consented for participation, and 31 completed 1-year follow-up. After initial consultation, 90% (n = 37) reported good/complete understanding of breast cancer risk. Of patients included in 1-year follow-up, 5 had DCIS, 13 had high-risk intraepithelial lesion, and 13 qualified based on Breast Cancer Risk Assessment Tool/International Breast Intervention Study calculation. Furthermore, 74% (n = 23) of patients reported that they took low-dose tam after consultation, with 78.2% (n = 18) of those still taking medication at 1 year. Patients who continued medication had higher estimated breast cancer risk compared with those who discontinued (International Breast Intervention Study 10-year risk, 12.7% vs. 7.6%; P = 0.027). All patients with DCIS initiated low-dose tam, and only one patient with DCIS had discontinued at 1 year. Uptake of low-dose tam after informed discussion is high. Adherence and tolerability at 1-year follow-up improved compared with those with traditional dosing of tam. Prevention Relevance: tam has been used extensively for breast cancer prevention in high-risk women. Historical uptake has been low because of concern for side effects and poor tolerability. Herein, we demonstrate that in the clinical setting, effective patient education and offering of a low-dose option can improve uptake in this high-risk population. See related Spotlight, p. 545.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"565-570"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395702","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":"Editors' Selections from Relevant Scientific Publications.","authors":"","doi":"10.1158/1940-6207.CAPR-17-12-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-17-12-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 12","pages":"543"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775315","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}