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

{"title":"Utilizing Human Genetics to Develop Chemoprevention for Cancer-Too Good an Opportunity to be Missed.","authors":"Ulrike Peters, Ian Tomlinson","doi":"10.1158/1940-6207.CAPR-22-0523","DOIUrl":"10.1158/1940-6207.CAPR-22-0523","url":null,"abstract":"<p><p>Large-scale genetic studies are reliably identifying many risk factors for disease in the general population. Several of these genetic risk factors encode potential drug targets, and genetics has already helped to introduce targeted agents for some diseases, an example being lipid-lowering drugs to reduce the incidence of cardiovascular disease. Multiple drugs have been developed to treat cancers based on somatic mutations and genomics, but in stark contrast, there seems to be a reluctance to use germline genetic data to develop drugs to prevent malignancy, despite the large numbers of people who could benefit, the potential for lowering cancer rates, and the widespread current use of non-pharmaceutical measures to reduce cancer risk factors such as tobacco, alcohol, and infectious diseases. We argue that concerted efforts for cancer prevention based on genetics, including genes influenced by common polymorphisms that modulate cancer risk, are urgently needed. There are enormous, yet underutilized, opportunities to develop novel targeted agents for chemoprevention of cancer based on human germline genetics. Such efforts are likely to require the support of a dedicated funding program by national and international agencies. See related commentary by Winham and Sherman, p. 13.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 1","pages":"7-12"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089482","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":"Leveraging GWAS: Path to Prevention?","authors":"Stacey J Winham, Mark E Sherman","doi":"10.1158/1940-6207.CAPR-23-0336","DOIUrl":"10.1158/1940-6207.CAPR-23-0336","url":null,"abstract":"<p><p>Developing novel cancer prevention medication strategies is important for reducing mortality. Identification of common genetic variants associated with cancer risk suggests the potential to leverage these discoveries to define causal targets for cancer interception. Although each risk variant confers small increases in risk, researchers propose that blocking those that produce causal carcinogenic effects might have large impacts on cancer prevention. While a promising concept, we describe potential hurdles that may need to be scaled to reach this goal, including: (i) understanding the complexity of risk; (ii) achieving statistical power in studies with binary outcomes (cancer development: yes or no); (iii) characterization of cancer precursors; (iv) heterogeneity of cancer subtypes and the populations in which these diseases occur; (v) impact of static genetic markers across complex events of the life course; (vi) defining gene-gene and gene-environment interactions and (vii) demonstrating functional effects of markers in human populations. We assess short-term prospects for this research against the backdrop of these challenges and the potential to prevent cancer through other means. See related commentary by Peters and Tomlinson, p. 7.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 1","pages":"13-18"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089480","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":"Recent American College of Physicians Guidance Statement for Screening Average-risk, Asymptomatic Adults for Colorectal Cancer.","authors":"Ernest T Hawk, Stephanie L Martch","doi":"10.1158/1940-6207.CAPR-23-0383","DOIUrl":"10.1158/1940-6207.CAPR-23-0383","url":null,"abstract":"<p><p>The American College of Physicians (ACP) update of their standing guidance statement for colorectal-cancer screening in asymptomatic average-risk adults was recently published to assist clinicians with implementing evidence-based patient care. After assessing existing guideline literature, the ACP recommended five actions: consider not screening adults ages 45 to 49 years; stop screening adults older than 75 years; discuss benefits, harms, costs, availability, frequency, and patient values/preferences with patients prior to choosing a screening method; and when choosing, recommend biennial rather than annual use of a fecal immunochemical test or a guaiac fecal occult blood test and avoid recommending computed tomography colonography or stool DNA tests. While the ACP guidelines are rigorous, well-intended, and considerate of patients' input, their greatest impact may result from highlighting the need for researchers to help frontline clinicians to describe the risk, costs, and benefits/harms of various colorectal-cancer screening strategies in an effective, yet time-efficient, manner given the all-too-brief annual patient encounters. In the United States, reimbursement is still dependent on U.S. Preventive Services Task Force recommendations which are somewhat more liberal in contrast to the ACP's approach which strongly favors randomized, controlled trial evidence to guide the delivery of prevention and screening services to asymptomatic average-risk patients.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089481","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":"Early-onset Colon Cancer Shows a Distinct Intestinal Microbiome and a Host-Microbe Interaction.","authors":"Darbaz Adnan, Jonathan Q Trinh, Deepak Sharma, Muhammad Alsayid, Faraz Bishehsari","doi":"10.1158/1940-6207.CAPR-23-0091","DOIUrl":"10.1158/1940-6207.CAPR-23-0091","url":null,"abstract":"<p><p>The incidence rate of colorectal cancer in younger adults has been rising in developed countries. This trend may be attributed to environmental exposures as a result of lifestyle changes. Many of the lifestyle factors that promote colorectal cancer can also affect the gut microbiome, which may be associated with colorectal cancer risks. The role of the microbiome in the ongoing rise of early-onset colorectal cancer is unknown. Here, we aimed to investigate age-related differences in the gut microbiome of patients with colorectal cancer and healthy individuals by examining both the fecal and tumor microbiomes. We utilized the publicly accessible data on fecal shotgun metagenomics from CuratedMetagenomeData and TCGA via the GDC Data Portal. Comparison of 701 colorectal cancer and 693 controls revealed that microbial features were age dependent, with a significant difference in species enrichment between early-onset (<50 years) and late-onset (>65 years) patients with colorectal cancer. Analysis of the tumor-associated microbiome in a separate dataset of 85 patients with colorectal cancer verified age-specific differences in taxon abundance between early- and late-onset patients with colorectal cancer. Finally, using host gene expression data, we found a stronger microbe-host interaction in early- vs. late-onset colorectal cancers. Altogether, these findings indicate that microbial features were age-dependent with stronger microbial-host interactions at the tumor site in early-onset colorectal cancers, suggesting a direct role of microbes in tumorigenesis via interaction with cancer-related pathways in this age group.</p><p><strong>Prevention relevance: </strong>Early-onset colorectal cancer is on the rise, presumably because of changes in environmental exposures. Lifestyle changes may contribute to colorectal cancer via alterations in gut microbes. Here, we show that microbial association with colorectal cancer is age-dependent, and microbe interactions with tumor pathways are stronger in young versus older colorectal cancers.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"29-38"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134650565","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":"Clinical Performance of hrHPV Primary Screening Using Vaginal versus Cervical Samples to Detect High-grade Intraepithelial Lesions.","authors":"Jonathan King, Yvonne N Flores, Joacim Meneses-León, Sonia Hernández-Salazar, Karina Robles-Rivera, Berenice Rivera-Paredez, Leith León-Maldonado, Rubí Hernández-López, Leticia Torres-Ibarra, Eduardo Lazcano-Ponce, Jorge Salmerón","doi":"10.1158/1940-6207.CAPR-23-0134","DOIUrl":"10.1158/1940-6207.CAPR-23-0134","url":null,"abstract":"<p><p>High-risk human papillomavirus (hrHPV) testing is now the most recommended primary method for cervical cancer screening worldwide. Clinician-collected cervical sampling continues to be the main sampling method, but hrHPV vaginal self-sampling is an appealing alternative because of its greater acceptability and potentially higher cost-effectiveness. This study aimed to determine whether hrHPV vaginal self-sampling is comparable with clinician-collected cervical sampling for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2/3) as part of a cervical cancer screening program in Mexico. We analyzed data from 5,856 women screened during a hrHPV-based screening study. Clinical performance and diagnostic efficiency metrics were estimated for the two sampling methods for the CIN3 and CIN2+ endpoints, using three triage strategies: HPV16/18 genotyping, HPV16/18/33/58 extended genotyping, and HPV16/18/31/33/58 extended genotyping. hrHPV-positivity was found in 801 (13.7%) cervical and 897 (15.3%) vaginal samples. All women with hrHPV-positive samples were referred to colposcopy, which detected 17 total CIN3 cases before considering retrospective triage strategies. Using the HPV16/18/31/33/58 extended genotyping strategy, 245 women had hrHPV-positive cervical samples and 269 had hrHPV-positive vaginal samples. Ten CIN3 cases were detected each among women with hrHPV-positive cervical samples and among those with hrHPV-positive vaginal samples when using this strategy, with no significant differences in sensitivity and specificity observed. We observe that self- and clinician-collected sampling methods are comparable for detecting CIN3 and CIN2+ regardless of the triage strategy used. These findings can help public health officials to develop more cost-effective cervical cancer screening programs that maximize participation.</p><p><strong>Prevention relevance: </strong>We found that hrHPV vaginal self-sampling is comparable with hrHPV clinician cervical sampling when using any triage strategy to refer women to colposcopy, so self-sampling is a viable cervical screening method. Therefore, policymakers should consider incorporating self-sampling into cervical screening programs to increase screening coverage and reduce cervical cancer burden. See related Spotlight, p. 649.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"681-687"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155269","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":"Knowledge Mediates the Effects of Game Changers for Cervical Cancer Prevention (GC-CCP) Intervention on Increased VIA Screening Advocacy in Uganda.","authors":"Glenn J Wagner, Joseph K B Matovu, Margrethe Juncker, Eve Namisango, Jolly Beyeza-Kashesya, Rhoda K Wanyenze","doi":"10.1158/1940-6207.CAPR-23-0262","DOIUrl":"10.1158/1940-6207.CAPR-23-0262","url":null,"abstract":"<p><p>Game Changers for Cervical Cancer Prevention (GC-CCP), a group advocacy training intervention, has been shown to increase cervical cancer prevention and screening advocacy. In this secondary analysis, we examined mediators and moderators of this effect. A randomized controlled trial of GC-CCP-a 7-session, peer led intervention designed to empower women to engage in cervical cancer prevention advocacy-was conducted with women who had recently been screened by visual inspection of the cervix with acetic acid for cervical cancer. Participants were assessed at baseline and month 6 follow-up. Cervical cancer-related constructs targeted by the intervention were examined as mediators using multivariate linear regression analysis. Individual and social network characteristics were examined as moderators. Change in cervical cancer knowledge fully mediated the intervention effect on increased cervical cancer prevention advocacy; change in cervical cancer risk management self-efficacy was a partial mediator. Moderators of the effect included no secondary education, having a main sex partner, and having trustworthy, supportive, non-stigmatizing peers. The effect of GC-CCP on cervical cancer prevention advocacy seems largely driven by its impact on cervical cancer knowledge, and the intervention may be most effective among women who are partnered, less educated, and have trusting, supportive social networks.</p><p><strong>Prevention relevance: </strong>Enhancing cervical cancer knowledge among women who have screened for cervical cancer is key to empowering these women to engage in cervical cancer prevention advocacy and acting as change agents for encouraging other women to screen.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"689-697"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41141852","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":"Comparing Breast Cancer and Cardiovascular Disease Risk and Use of Chemoprevention and Statins among Women with High-risk Breast Lesions.","authors":"Kehinde O Lawal, Luisa Nilan, Jacquelyn Amenta, Julia E McGuinness, Rita Kukafka, Katherine D Crew","doi":"10.1158/1940-6207.CAPR-23-0181","DOIUrl":"10.1158/1940-6207.CAPR-23-0181","url":null,"abstract":"<p><p>Breast cancer chemoprevention with selective estrogen receptor modulators (SERM) or aromatase inhibitors (AI) remains underutilized among high-risk women. A potential barrier to chemoprevention is competing comorbidities such as atherosclerotic cardiovascular disease (ASCVD), due to concern for additional medication side effects. We conducted a retrospective cohort study among women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), an important target population for chemoprevention. We compared risks for breast cancer and ASCVD, as well as use of SERMs/AIs versus statins among high-risk women (defined as a 5-year invasive breast cancer risk ≥1.67% and 10-year ASCVD risk ≥7.5%, respectively). We used clinical data extracted from the electronic health record to calculate breast cancer risk according to the Breast Cancer Surveillance Consortium model and ASCVD risk according to the 2013 American College of Cardiology/American Heart Association risk calculator. Among 298 evaluable women, mean age was 58.2 years (SD, 8.34), with 33% non-Hispanic White, 41% Hispanic, 9% non-Hispanic Black, 6% Asian, and 11% other/unknown race/ethnicity. About 98% of women met high-risk criteria for breast cancer, whereas 30% were high-risk for ASCVD. Mean 10-year risk of breast cancer was higher than mean 10-year risk of ASCVD (9.14% vs. 6.69%; P < 0.001). Among women who met high-risk criteria for both diseases, use of statins was higher compared with SERMs/AIs (58% vs. 21%; P < 0.001). Among women with AH or LCIS, statin use was higher compared with breast cancer chemoprevention among eligible women, despite having a higher mean risk of breast cancer than ASCVD.</p><p><strong>Prevention relevance: </strong>Among women with high-risk breast lesions, mean absolute risk of breast cancer was higher compared with cardiovascular disease; however, statin use was significantly higher than chemoprevention. To address underutilization of breast cancer chemoprevention, these drugs should be placed in the context of medications used to prevent other chronic diseases.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"661-667"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136400604","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":"Cancer Prevention Perspective: The University of Kansas Cancer Center.","authors":"Roy A Jensen, Christie A Befort","doi":"10.1158/1940-6207.CAPR-22-0418","DOIUrl":"10.1158/1940-6207.CAPR-22-0418","url":null,"abstract":"<p><p>Despite the incredible progress that has been made against cancer over the last few decades, the demographic trends in the United States predict that we will see significant increases in cancer incidence and mortality by the year 2030. This, coupled with an aging cancer workforce, would suggest that we will have major challenges ahead in dealing with the increasing burden from cancer. Clearly a critical part of our strategy must be to focus on cancer prevention and control (CPC) efforts and not solely rely on treatment to mitigate this concerning trend. This review discusses how the University of Kansas Cancer Center has had a longstanding emphasis on CPC and has leveraged this expertise to enhance the effectiveness and impact of our community outreach and engagement efforts.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"16 12","pages":"643-647"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464754","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":"A Novel Saliva and Serum miRNA Panel as a Potential Useful Index for Oral Cancer and the Association of miR-21 with Smoking History: a Pilot Study.","authors":"Dimitra P Vageli, Panagiotis G Doukas, Rema Shah, Trinithas Boyi, Christina Liu, Benjamin L Judson","doi":"10.1158/1940-6207.CAPR-23-0219","DOIUrl":"10.1158/1940-6207.CAPR-23-0219","url":null,"abstract":"<p><p>Tobacco use is implicated in the carcinogenesis of oral squamous cell carcinoma (OSCC), which is associated with poor survival if not diagnosed early. Identification of novel noninvasive, highly sensitive, and cost-effective diagnostic and risk assessment methods for OSCC would improve early detection. Here, we report a pilot study assessing salivary and serum miRNAs associated with OSCC and stratified by smoking status. Saliva and paired serum samples were collected from 23 patients with OSCC and 21 healthy volunteers, with an equal number of smokers and nonsmokers in each group. Twenty head and neck cancer-related miRNAs were quantified by qPCR (dual-labeled LNA probes) and analyzed by Welch t test (95% confidence interval). Four saliva miRNAs, miR-21, miR-136, miR-3928, and miR-29B, showed statistically significant overexpression in OSCC versus healthy controls (P < 0.05). miR-21 was statistically significantly overexpressed in OSCC smokers versus nonsmokers (P = 0.006). Salivary miR-21, miR-136, and miR-3928, and serum miR-21 and miR-136, showed statistically significant differential expression in early-stage tumors versus controls (P < 0.05), particularly miR-21 in smokers (P < 0.005). This pilot study provides a novel panel of saliva and serum miRNAs associated with oral cancer. Further validation as a potential useful index of oral cancer, particularly miR-21 in smokers and early-stage OSCC is warranted.</p><p><strong>Prevention relevance: </strong>Saliva and serum miR-21, miR-136, miR-3928, and miR-29B, are potentially associated with oral cancer even at an early stage, especially miR-21 in individuals with a smoking history, a further validation in a larger cohort of subjects with premalignant and early malignant lesions need to confirm.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"653-659"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177766","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":"Treatment of Cervical Precancers is the Major Remaining Challenge in Cervical Screening Research.","authors":"Kanan T Desai, Silvia de Sanjosé, Mark Schiffman","doi":"10.1158/1940-6207.CAPR-23-0448","DOIUrl":"10.1158/1940-6207.CAPR-23-0448","url":null,"abstract":"<p><p>Deepening understanding of cervical cancer pathogenesis has yielded one-dose prophylactic human papillomavirus (HPV) vaccines and accurate HPV-based cervical screening tests. Knowing the heterogeneous carcinogenic potential of the individual high-risk HPV types permits prioritization of vaccination and screening strategies. However, \"correct\" (i.e., safe and effective) treatment of women found to have precancer is still undefined, forcing reliance on one or more rounds of untargeted destructive/excisional treatment. Both over-treatment and under-treatment are common results. Until safe and effective anti-HPV therapies are invented, defining optimal destructive/excisional treatment of precancer remains a fundamental and under-researched challenge, especially in resource-constrained settings. See related article by King et al., p. 681.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"16 12","pages":"649-651"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464755","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}