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

Colorectal cancer (CRC) is highly preventable with timely screening, but screening modalities are widely underused, especially among those of low individual-level socioeconomic status (SES). In addition to individual-level SES, neighborhood-level SES may also play a role in CRC screening completion through less geographic access to health care, transportation, and community knowledge of and support for screenings. We investigated the associations between neighborhood SES using a census tract-level measure of social and economic conditions with the uptake of colonoscopy and stool-based testing. We utilized data from the Southern Community Cohort Study, a large, prospective study of English-speaking adults aged 40-79 from the southeastern United States with 65% of participants identifying as non-Hispanic Black and 53% having annual household income <$15,000. Neighborhood SES was measured via a Neighborhood Deprivation Index compiled from principal component analysis of 11 census tract variables in the domains of education, employment, occupation, and poverty; screening was self-reported at the baseline interview (2002-2009) and follow-up interview (2008-2012). We found that participants residing in the lowest SES areas had lower odds of ever undergoing colonoscopy (ORQ5vsQ1=0.75; 95%CI=[0.68, 0.82]) or stool-based CRC testing (ORQ5vsQ1=0.71; 95%CI=[0.63, 0.80]), while adjusting for individual-level SES factors. Associations were consistent between neighborhood SES and screening in subgroups defined by race, sex, household income, insurance, or education (p>0.20 for all interaction tests). Our findings suggest that barriers to screening exist at the neighborhood level and that residents of lower SES neighborhoods may experience more barriers to screening using colonoscopy and stool-based modalities.

Screening digital breast tomosynthesis (DBT) aims to identify breast cancer early when treatment is most effective leading to reduced mortality. In addition to early detection, the information contained within DBT images may also inform subsequent risk stratification and guide risk-reducing management. Using transfer learning we refined a model in the WashU cohort of 5,066 women with DBT screening (mean age 54.6) among whom 105 were diagnosed with breast cancer (26 DCIS). We applied the model to external data from the EMBED cohort of 7,017 women free from cancer (mean age 55.4) among whom 111 pathology confirmed breast cancer cases were diagnosed more than 6 months after initial DBT (17 DCIS). We obtained a 5-year area under the curve (AUC) = 0.75 (95% confidence interval (CI) = 0.73 - 0.78) in the internal validation. The model validated in external data gave an AUC = 0.72 (95% CI, 0.69 - 0.75). The AUC was unchanged when age and BI-RADS density are added to the model with synthetic DBT image. The model significantly outperforms the Tyrer-Cuzick model 5-year AUC 0.56 (95%CI 0.54, 0.58) (p<0.01). Our model extends risk prediction applications to synthetic DBT, provides 5-year risk estimates, and is readily calibrated to national risk strata for clinical translation and guideline driven risk management. The model could be implemented within any digital mammography program.

Experimental studies have shown dietary isothiocyanates reduced cellular proliferative marker Ki-67 and increased apoptotic markers Caspase-3 and TUNEL in animals, but human data are lacking. The present study was to assess whether sulforaphane would stop/reverse the progression of bronchial histopathology, reduce Ki-67 index and/or increase Caspase-3 and TUNEL indices in humans. A randomized clinical trial (NCT03232138) was conducted in former smokers. Forty-three subjects were randomly assigned to the placebo or the treatment with a potential daily dose of 95 µmol sulforaphane for 12 months. The endpoints were the changes of histopathology scores, and Ki-67, Caspase-3 and TUNEL indices in post- vs. pre-treatment bronchial biopsies. Thirty-seven participants (17 in the sulforaphane and 20 in the placebo group) completed the study. Supplementation of sulforaphane did not show significant impact on bronchial histopathology, but significantly reduced Ki-67 index with a 20% decrease in the sulforaphane group and a 65% increase in the placebo (p = 0.014). The difference was even greater in high-density (3+) positive Ki-67, with a 44% decrease in the sulforaphane group compared with a 71% increase in the placebo (p = 0.004). Higher bioavailability of sulforaphane was correlated with greater reduction of Ki-67 index (P for trend = 0.019). Sulforaphane treatment had no impact on Caspase-3 or TUNEL index in bronchial biopsies. No severe adverse event was observed in the study participants. The findings of oral sulforaphane that significantly reduced Ki-67 index in bronchial tissue support further development as a potential chemopreventive agent against lung cancer development.

Aspirin reduces colorectal cancer risk but has a potential for adverse effects. Recent pre-clinical data suggest that intermittent dosing of aspirin may minimize adverse effects maintaining efficacy. We conducted a three-arm double-blind randomized placebo-controlled Phase II trial. The primary objective of the study was to test for the equivalency of the two aspirin schedules, i.e., the effects of daily aspirin 325 mg/day continuously (cont-ASA) for 12 weeks or intermittently, 3-weeks on/3-weeks off (int-ASA) on biomarkers related to colorectal carcinogenesis in rectal mucosa. A placebo group enabled the estimation of spontaneous biomarker variation. 81 participants were randomized, of whom 45 were evaluable. For the primary endpoint of decrease in the Ki-67:BAX ratio, we could not establish equivalence for the two treatment regimens, and also found no significant difference between them. For the secondary endpoint, cont-ASA treatment was significantly more effective in reducing Ki-67:TUNEL ratio. Among exploratory endpoints, we found more reduction in epithelial COX-2 expression in cont-ASA arm compared to int-ASA arm. We did not observe significant differences in other secondary and exploratory endpoints. Intermittent aspirin dosing in 3-week cycles does not produce the same biologic effect as continuous dosing. Future studies should examine whether the 1-week on/1-week off schedule can maximize the efficacy and minimize the side effects.

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.

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.

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.

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.

The Tribally-Engaged Approaches to Lung Cancer Screening (TEALS) study aimed to co-design and test a community-based lung cancer screening (LCS) program within a large, tribally operated health system. In 2020-2021, we conducted a pre-post quasi-experimental pilot implementation study of a tailored and comprehensive LCS program in two Choctaw Nation of Oklahoma (CNO) primary care clinics in rural Oklahoma. The program included screening quality assessment, academic detailing, practice facilitation, health system enhancements, technology support, centralized LCS coordination, and community outreach. Eligibility for LCS was based on the 2013 US Preventive Services Task Force guidelines. Participants completed pre- and post-intervention surveys on their knowledge, attitudes, and experiences regarding LCS. All participant charts were extracted to determine LCS completion. Post-implementation semi-structured interviews of patients and clinicians were conducted and practice facilitator notes were analyzed. Participants (N=57) averaged 67 years, and 66% were current smokers. The proportion of participants who were up to date with LCS increased from 39% to 58% (p<0.01). About 18% of patients reported improvement in general care choice and treatment discussions with their doctor and about 40% reported an improvement in their awareness or understanding of lung cancer and receipt of LCS. We also identified several key facilitators and barriers to LCS implementation at the practice and health system levels. LCS acceptance and uptake improved significantly in this community-engaged pilot intervention which informed a subsequent cluster-randomized trial. Comprehensive and community-engaged LCS programs may have the potential to improve the delivery of LCS in underserved community settings.