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

Historically, cancers diagnosed via the Emergency Department (ED) portend a poor prognosis. Recent data from the United States (U.S.) are sparse and analyses of cancers detected in the years following ED visits are lacking. Thus, we analyzed data from 9 rural Midwest U.S. counties included within the population-based Rochester Epidemiology Project (REP) (2015-2021). Participants without a history of cancer (N=42,074) who did not receive ED care were matched 1:1 to ED participants on date of ED visit, age, sex, race, ethnicity and county of residence. Analyses were restricted to participants with records <2 years prior to ED or index visit and > 30 days after. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing cancer incidence and deaths among ED and non-ED participants were estimated from Cox proportional hazards regression models, either unadjusted or adjusted for covariates. Cumulative cancer incidence curves accounting for competing risks of death and survival (all cause and cancer-specific) were estimated. Median follow-up was 6.3 years, with 2719 (6.46%) cancers diagnosed among ED participants and 3139 (7.46%) among non-ED participants. ED participants experienced lower cancer risk overall (HRAdjusted=0.70, 95%CI: 0.66-0.74; p=8.89 X10-31), and specifically for breast cancer, prostate cancer, melanoma and secondary cancers. Cancer-specific mortality was higher among ED participants (HRAdjusted=1.76, 95%CI: 1.49-2.08; p=3.62X10-11). Compared with non-ED participants, ED participants experienced a lower incidence of cancer but higher overall cancer-specific mortality, suggesting that subsets of ED patients may benefit from post-visit preventive interventions.

The role of dietary fiber in colon cancer prevention remains controversial. We investigated its impact on antitumor immunity and the gut microbiota in APCmin/+ mice infected with enterotoxigenic Bacteroides fragilis. Mice were fed high-fiber, low-fiber, or chow diets, and the tumor burden, survival, cytokines, microbiota, and metabolites were analyzed. Contrary to the belief that high fiber inhibits tumor progression, it had no significant impact compared with chow diet. However, the low-fiber diet significantly reduced the tumor burden and improved survival. Mechanistically, high fiber increased proinflammatory cytokines and CD4+Foxp3+RORγt+IL-17A+ regulatory T cells, whereas low fiber enhanced anti-inflammatory cytokines and cytotoxic T cells. High fiber enriched microbial taxa associated with IL-17A+RORγt+ regulatory T cells and altered metabolites, including reduced tryptophan and increased short-chain fatty acids and bile acids. Low fiber produced opposite effects. These findings suggest that dietary fiber's effects on colon cancer depends on microbial infection and immune status, emphasizing the need for personalized dietary interventions in colon cancer management. Prevention Relevance: Dietary fiber's impact on colon cancer progression highlights the need for personalized dietary approaches, considering microbial infection and immune status.

Given the female predominance of thyroid cancer, particularly in the reproductive age range, female sex hormones have been proposed as an etiology; however, previous epidemiological studies have shown conflicting results. We conducted a pooled analysis using individual data from nine prospective cohorts in the Asia Cohort Consortium to explore the association between 10 female reproductive and hormonal factors and thyroid cancer risk. Using Cox proportional hazards models, cohort-specific hazard ratios (HR) and 95% confidence intervals (CI) were estimated and then pooled using a random-effects model. Analyses were stratified by country, birth years, smoking status, and body mass index, and thyroid cancer risk based on age of diagnosis was also examined. Among 259,649 women followed up for a mean of 17.2 years, 1,353 incident thyroid cancer cases were identified, with 88% (n = 1,140) being papillary thyroid cancer. Older age at first delivery (≥26 vs. 21-25 years) was associated with increased thyroid cancer risk (P-trend = 0.003; HR = 1.16; 95% CI, 1.03-1.31), particularly when diagnosed later in life (≥55 vs. < 55 years; P-trend = 0.003; HR = 1.19; 95% CI, 1.02-1.39). Among younger birth cohorts, women with more number of deliveries showed an increased thyroid cancer risk [P-trend = 0.0001, HR = 2.40; 95% CI, 1.12-5.18 (≥5 vs. 1-2 children)], and there was no substantial trend in older cohorts. Distinct patterns were observed for the number of deliveries and thyroid cancer risk across countries, with a significant positive association for Korea [P-trend = 0.0008, HR = 1.89; 95% CI, 1.21-2.94 (≥5 vs. 1-2 children)] and nonsignificant inverse associations for China and Japan. Contextual and macrosocial changes in reproductive factors in Asian countries may influence thyroid cancer risk. Prevention Relevance: This analysis of prospective cohort studies across three Asian countries highlights that older age at first birth is linked to increased thyroid cancer risk. As women delay motherhood, understanding these trends is vital for public health strategies addressing reproductive factors influencing thyroid cancer risk in these populations.

Oral cancer is a major global health problem. It is commonly diagnosed at an advanced stage, although often preceded by clinically visible oral mucosal lesions, termed oral potentially malignant disorders, which are associated with an increased risk of oral cancer development. There is an unmet clinical need for effective screening tools to assist front-line healthcare providers to determine which patients should be referred to an oral cancer specialist for evaluation. This study reports the development and evaluation of the mobile detection of oral cancer (mDOC) imaging system and an automated algorithm that generates a referral recommendation from mDOC images. mDOC is a smartphone-based autofluorescence and white light imaging tool that captures images of the oral cavity. Data were collected using mDOC from a total of 332 oral sites in a study of 29 healthy volunteers and 120 patients seeking care for an oral mucosal lesion. A multimodal image classification algorithm was developed to generate a recommendation of "refer" or "do not refer" from mDOC images using expert clinical referral decision as the ground truth label. A referral algorithm was developed using cross-validation methods on 80% of the dataset and then retrained and evaluated on a separate holdout test set. Referral decisions generated in the holdout test set had a sensitivity of 93.9% and a specificity of 79.3% with respect to expert clinical referral decisions. The mDOC system has the potential to be utilized in community physicians' and dentists' offices to help identify patients who need further evaluation by an oral cancer specialist. Prevention Relevance: Our research focuses on improving the early detection of oral precancers/cancers in primary dental care settings with a novel mobile platform that can be used by front-line providers to aid in assessing whether a patient has an oral mucosal condition that requires further follow-up with an oral cancer specialist.

Despite increasing incidence of hepatocellular carcinoma (HCC) in vulnerable populations, accurate early detection tools are lacking. We aimed to investigate the associations between prediagnostic plasma metabolites and incident HCC in a diverse population. In a prospective, nested case-control study within the Southern Community Cohort Study, we conducted prediagnostic LC/MS metabolomic profiling in 150 incident HCC cases (median time to diagnosis, 7.9 years) and 100 controls with cirrhosis. Logistic regression assessed metabolite associations with HCC risk. Metabolite set enrichment analysis identified enriched pathways, and a random forest classifier was used for risk classification models. Candidate metabolites were validated in the UK Biobank (N = 12 incident HCC cases and 24 cirrhosis controls). In logistic regression analysis, seven metabolites were associated with incident HCC (MeffP < 0.0004), including N-acetylmethionine (OR = 0.46; 95% confidence interval, 0.31-0.66). Multiple pathways were enriched in HCC, including histidine and CoA metabolism (FDR P < 0.001). The random forest classifier identified 10 metabolites for inclusion in HCC risk classification models, which improved HCC risk classification compared with clinical covariates alone (AUC = 0.66 for covariates vs. 0.88 for 10 metabolites plus covariates; P < 0.0001). Findings were consistent in the UK Biobank (AUC = 0.72 for covariates vs. 0.88 for four analogous metabolites plus covariates; P = 0.04), assessed via nuclear magnetic resonance spectroscopy. Prediagnostic metabolites, primarily amino acid and sphingolipid derivatives, are associated with HCC risk and improve HCC risk classification beyond clinical covariates. These metabolite profiles, detectable years before diagnosis, could serve as early biomarkers for HCC detection and risk stratification if validated in larger studies. Prevention Relevance: Our findings support the need for larger prospective studies examining the role of prediagnostic plasma metabolomics for the preventive management of HCC in diverse patients across multiple etiologies of liver disease. This approach could improve HCC care by identifying metabolic changes years before diagnosis, potentially enhancing screening and early detection practices.

Individuals living with human immunodeficiency virus (HIV) are at a higher risk for developing human papillomavirus-driven oropharyngeal squamous cell carcinoma (HPV + OPSCC). There are no methods for early detection; however, HPV16 E6 antibodies have been identified as a promising early marker. The objective of this study was to evaluate the prevalence of HPV16 E6 antibodies among men living with HIV, with secondary objectives of analyzing clinical and serologic predictors of HPV16 E6 seropositivity. Banked blood specimens from 2,320 men ages ≥40 years living with HIV in Tennessee were evaluated for the following HPV16 antibodies: L1, E1, E2, E4, E6, and E7. HPV16 E6 antibody levels were further categorized as moderate or high. Demographic, clinical, and serologic determinants of HPV16 E6 seropositivity were evaluated using logistic regression. HPV16 L1 antibodies were most common (22.8%), followed by E4 (10.5%), E6 (5.6%), E2 (4.8%), and E7 (4.0%). Of the 130 HPV16 E6 seropositives, 55 (2.4%) had moderate and 75 (3.2%) had high seropositivity. HPV16 E6 seropositive men had nearly twofold greater odds of seropositivity against one additional HPV16 E antigen [OR: 1.67 (95% CI, 1.10-2.52); P = 0.015] and more than threefold greater odds of seroreactivity against two additional HPV16 E antigens [OR: 3.21 (95% CI, 1.40-7.33); P = 0.006]. HPV16 E6 seropositivity was not associated with the clinical or demographic factors evaluated. In the largest study to date, HPV16 E6 seroprevalence was elevated compared with prior studies in HIV populations (range: 1.1%-3.2%) and likely reflects the high incidence of HPV + OPSCC in the Southeast region of the United States. Prevention Relevance: Our findings fill an important gap, given that our study is the largest to date to evaluate HPV antibodies among men living with HIV and is the first study to do so in the Southeastern United States, the region with the highest prevalence of both HIV and HPV + OPSCC in the nation.

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.

Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Only a minority of MGUS patients will develop MM, but precise prediction of progression is impossible using routine clinical biomarkers. Changes in the levels of blood immune markers can help predict disease progression. Data remain inconsistent for some markers of interest such as monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1α), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), fractalkine, and transforming growth factor-alpha (TGF-α). We aimed to investigate the associations between the pre-diagnostic serum levels of these candidate biomarkers and future MM risk, as well as to assess marker changes over time. We performed a nested case-control study using prospective samples from the Janus Serum Bank in Norway to investigate associations between MM risk and pre-diagnostic serum levels of MCP-3, MIP-1α, FGF-2, VEGF, fractalkine, and TGF-α. The study included 293 future MM cases with serum samples collected 20 years (median) before MM diagnosis and 293 matched cancer-free controls. MM patients had an additional pre-diagnostic sample collected up to 42 years before diagnosis to identify marker changes over time. Markers with >60% detection rate (MIP-1α, VEGF, and TGF-α) were included in the statistical analysis. We observed no statistically significant associations between MM risk and serum levels of MIP-1α, VEGF, or TGF-α in samples collected 20 years before diagnosis. However, TGF-α levels decreased significantly closer to the diagnosis in MM patients (p<0.001). The decrease in TGF-α levels may reflect subtle microenvironmental changes related to MM progression.

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.