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

Timely diagnosis and intervention in colorectal cancer are critical to improving patient outcomes and limiting disease progression. Screening of average-risk individuals is essential for detecting tumors at an earlier, more treatable stage. However, adherence to current screening programs remains suboptimal. Liquid biopsies represent a promising alternative to stool-based tests and may play a key role in optimizing colorectal cancer detection and diagnostic pathways. In this study, 957 patients were recruited across various clinical sites in the United States: 48 with colorectal cancer, 157 with advanced precancerous lesions (APL), 331 with nonadvanced lesions, and 421 with a negative colonoscopy diagnosis. Blood was obtained from patients either prior to scheduled colonoscopy or before surgical resection and any anticancer therapies. Streck plasma samples were analyzed by the Dxcover Liquid Biopsy Platform and classified using machine learning algorithms. When colorectal cancer was classified against all other groups, the ROC curve generated an AUC value of 0.95, and test sensitivity and specificity were 90% and 89%, respectively. The diagnostic model accurately predicted 75% of stage I (3/4), 100% of stage II (15/15), 93% of stage III (14/15), and 100% of stage IV (6/6) colorectal cancers. For the advanced colorectal neoplasia model, 29% of APL were detected. A simple blood test with high sensitivity for early-stage colorectal cancer could significantly enhance patient outcomes. With continued development, this liquid biopsy has the potential to make a substantial impact on the early detection of colorectal cancer.

Prevention relevance: Timely diagnosis and intervention in colorectal cancer are critical to improving patient outcomes. A simple blood test with high sensitivity for early-stage colorectal cancer could significantly enhance patient outcomes. With continued development, this liquid biopsy has the potential to make a substantial impact on the early detection of colorectal cancer.

Fatty acid synthesis pathway is a valid target for prevention of prostate cancer. However, a clinical grade inhibitor of fatty acid synthesis is still lacking. This bench-to-bedside study was undertaken to determine the feasibility of fatty acid synthesis inhibition using broccoli constituent sulforaphane (SFN) and its clinical grade formulation BroccoMax® (BMAX). Oral administration of SFN to Hi-Myc mice resulted in inhibition of prostate adenocarcinoma burden by about 61% that was accompanied by a significant decrease in prostate tumor levels of c-Myc and PCNA proteins and increased apoptosis. Expression of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN) were lower by about 46% and 31%, respectively, in the prostate tumor of SFN-treated mice when compared to that of control mice (P < 0.001). Plasma levels of total free fatty acids (TFFA), cholesterol, and total phospholipids were decreased significantly following SFN treatment. In a double-blind clinical trial, patients with histologically confirmed prostate cancer were randomized to the BMAX group (n= 19) or placebo group (n= 22). Patients were treated with 4 capsules BMAX or 4 capsules of matching placebo orally two times daily after breakfast and dinner for 4 weeks. Prostate tumor expression of c-Myc, ACC1, FASN, and Ki-67 proteins were significantly lower in the BMAX arm when compared to PBO group. However, serum or prostate tumor level of acetyl-CoA or TFFA was not decreased by BMAX treatment. A longer duration treatment with BMAX in early-stage prostate cancer patients may be necessary to lower circulating or prostate tumor level of TFFA.

Colorectal cancer (CRC) remains a significant public health concern, particularly among underserved populations. This study evaluated CRC risk factors and compared risk assessment models in a predominantly Hispanic cohort residing along the U.S.-Mexico border. We analyzed data from 4,202 CRC screening participants, mostly women (78.3%), with a mean age of 57.3 years (SD = 5.54). Most were born in Mexico (86.2%) and had resided in the U.S. for an average of 25 years (SD = 16.5). Risk was assessed using four models: Freedman, Wells, Kaminski, and Yeoh. We examined model concordance, risk distributions, and gender-specific trends. Freedman's model showed that 41.1% of participants had a lifetime CRC risk above the national average. Men had a higher lifetime risk (51.3%) than women (38.3%), while more women had elevated 10-year risk (26.3% vs. 21.1%). Freedman and Wells models demonstrated a strong concordance correlation coefficient (CCC = 0.76), with an optimal Freedman cutoff of 0.97 (AUC = 87%). Kaminski and Yeoh identified more participants at above-average risk (27.8% and 35%) compared to Freedman (20.6%) and Wells (14.9%). Key contributors to elevated risk included smoking pack-years, obesity, and family history, with gender-specific variations. Freedman's model, offering both lifetime and 10-year risk estimates, emerged as the most practical tool in this cohort. Custom thresholds (0.89 for women, 1.41 for men) improved risk stratification, aligning with validated polyp-detection rates. These findings support the use of tailored CRC risk models for Hispanic populations to enhance targeted screening and prevention efforts.

Early detection efforts in gastric carcinoma focus on identifying those with gastric premalignant conditions (GPMC), as they may benefit from secondary prevention. Noninvasive identification of persons with GPMC is an ideal avenue, but currently, no such strategy exists. Although persons with cytotoxin-associated gene A (CagA; the most well-known virulence factor in Helicobacter pylori infection) may be more prone to GPMC, CagA has traditionally been limited to research settings. Recently, a novel point-of-care (POC) test for CagA was developed. In this study, we report on the clinical utility of this test. We evaluated samples from adults undergoing preplanned endoscopy between 2023 and 2025 for benign indications to evaluate the association between GPMC and CagA antibody positivity. Among 95 persons, we found that 40% had H. pylori infection, 14% had GPMC, and 41% had CagA antibody positivity. There was a nonsignificant association between CagA antibody positivity and GPMC [odds ratio (OR) = 1.68; 95% confidence interval (CI), 0.48-5.85; P = 0.42]. In those without active H. pylori, the OR for CagA antibody positivity was 0.78 (95% CI, 0.13 to 4.73; P = 0.79), whereas in those with H. pylori, the OR for CagA antibody positivity was 3.46 (95% CI, 0.29 to 41.52; P = 0.33). We found nonsignificant associations between CagA antibody positivity and GPMC and active H. pylori infection may represent an important effect modifier. Our data suggest that although larger-scale validation is needed, a risk-guided screening strategy could include first testing for active H. pylori infection (e.g., breath or stool test), and if positive, POC testing for CagA antibodies.

Prevention relevance: Early detection of gastric cancer is sorely needed, and a risk-stratified approach to detecting which persons are likely to have gastric premalignant lesions and may benefit from endoscopy is the optimal secondary surveillance strategy.

Ovarian cancer is the leading cause of death among gynecologic cancers because of its late diagnosis, but risk stratification for targeted prevention can improve outcomes. To identify women at risk of ovarian cancer, pathogenic variant testing is used, especially for those with a family history of the disease. However, high-risk genetic variants are rare, accounting for <20% of ovarian cancer cases overall. More recently, clinical models that help identify ovarian cancer cases incorporate polygenic risk for improved risk stratification. Herein, we cross-validate a polygenic risk-integrated clinical model called the refined risk model in a nested case-control population from the Nurses' Health Study. The refined risk model is compared with a clinical risk score and polygenic risk score model, respectively. The ORs per SD were 1.26 (1.01, 1.48), 1.13 (0.96, 1.33), and 1.22 (1.04, 1.43) with corresponding AUCs of 0.56 (0.51, 0.61), 0.54 (0.49, 0.59), and 0.55 (0.50, 0.60) for the refined risk, clinical risk, and polygenic risk models, respectively. Population screening has been assessed over the years, and although stage-shifting in the screened population has occurred, the mortality benefit was not evident. However, as treatments for ovarian cancer improve, the benefits of a risk-stratified approach to screening are expected to grow.

Prevention relevance: In this study, we have validated the predictive performance of a combined clinical and polygenic model for ovarian cancer. Accurate risk assessment enables more efficient allocation of preventive interventions, including intensified surveillance and consideration of risk-reducing salpingo-oophorectomy among women at elevated risk.

Head and neck squamous cell carcinoma (HNSCC) is among the 10 most common cancers worldwide and is associated with high morbidity and poor survival. Diminished HNSCC outcomes are often related to delayed diagnosis and treatment of occult progression of premalignant lesions, underscoring the need for effective and low-risk chemoprevention strategies. In this regard, metformin has shown promising clinical activity for HNSCC prevention. In this study, we performed a genome-wide CRISPR/Cas9 screen of metformin-treated HNSCC cells and identified the activation of PKA signaling as the top resistance pathway. We show that metformin mediates PKA activation in HNSCC cells and that PKA inhibition, when combined with metformin treatment, synergistically inhibits HNSCC growth. We found that metformin-induced PKA activation is mediated by a prostaglandin E2 autocrine loop, which can be blocked using cyclooxygenase-2 (COX2) inhibitors. Importantly, COX2 inhibition using nonsteroidal anti-inflammatory drugs (NSAID) combined with metformin treatment synergistically inhibits HNSCC cell growth and prevents the progression of oral premalignant lesions into invasive HNSCC in a model of tobacco-driven oral carcinogenesis. Together, these findings demonstrate that metformin and NSAID combination therapy may represent a promising therapeutic strategy for HNSCC chemoprevention.

Prevention relevance: Our findings reveal that using metformin for head and neck cancer chemoprevention leads to compensatory activation of a PKA-driven resistance mechanism that can be blocked by cotreatment with NSAIDs. These findings provide a rationale for combining metformin with NSAIDs as a precision head and neck cancer chemoprevention strategy.

The increasing prevalence and aggressive, potentially fatal, nature of early-onset colorectal cancer (EOCRC) makes it critical to identify risk factors that can facilitate earlier screening and detection. With electronic medical record data, we compared adults ages 20 to 49 years diagnosed with EOCRC (2017-2023) to control patients without EOCRC who were 1:2 exact-matched based on age and sex. We extracted data on patients' sociodemographics, comorbidities, hereditary syndromes, family history, symptoms, specialty visits, and medications within 12 to 24 months prior to or on their diagnostic visit. Using a model-building approach, we analyzed data with univariate then multivariate logistic regressions to predict the odds of EOCRC diagnosis. We constructed three models using high-risk background characteristics as predictors (baseline and high-risk) and exclusion criteria (sporadic), respectively. Our final analysis included 684 EOCRC cases and 1,368 controls. The mean age was 42 years, with 53% male, 72% White, and 72% non-Hispanic/Latino. Across all models, several predictors were significantly associated with higher EOCRC odds, including alcohol use history, higher number of comorbidities, abdominal pain, rectal bleeding, constipation, iron deficiency anemia, and prescriptions for metformin, non-steroidal anti-inflammatory drugs (NSAID), and multivitamins. Significant predictors of lower EOCRC odds were employment and Medicare/Medicaid insurance. By concurrently including symptoms, medical history, and sociodemographic characteristics, we constructed and validated well-fitting models with good discrimination that replicated and extended prior case-control research. To facilitate earlier screening and detection, these EOCRC risk factors can be used to identify patients who would benefit from screening earlier than 45 years of age.

Prevention relevance: There is a need for risk stratification models that simultaneously consider symptoms, medical history, and sociodemographic characteristics. This study identified a set of risk factors that can be used to recommend early screening to symptomatic and asymptomatic patients below the age of 45, even among those without high-risk familial background.