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

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.

The 2025 Kennedy v. Braidwood Supreme Court decision upheld the Affordable Care Act mandate requiring insurance coverage of preventive services with an A/B rating from the U.S. Preventive Services Task Force (USPSTF) without cost-sharing. This ruling preserved access to essential preventive care, including colorectal cancer screening, a leading cause of cancer-related mortality despite the availability of effective, evidence-based screening methods. The recent elimination of out-of-pocket costs for follow-up colonoscopy after positive stool testing resulted in an absolute increase of 1.48% in follow-up procedures, highlighting the impact of financial barriers on the completion of the screening continuum. Yet nonfinancial barriers such as limited transportation, language barriers, and scheduling challenges persist. Patient navigation services addressing these barriers have demonstrated substantial improvements in screening adherence and diagnostic completion but remain inconsistently covered. Recent federal policies about breast and cervical cancer screening have expanded the definition of screening to include follow-up care and navigation services, now requiring coverage of these services by private insurers and Medicaid without cost-sharing. Colorectal cancer screening coverage should similarly expand to include these critical support services. Aligning policy with the realities of patient access will enhance screening uptake, reduce disparities, and strengthen the cost-effectiveness of colorectal cancer prevention efforts.

Statins may reduce hepatocellular carcinoma (HCC) risk regardless of metabolic dysfunction-associated steatotic liver disease (MASLD) status. However, it remains unclear whether long-term statin use in MASLD patients lowers HCC risk to levels seen in individuals without steatotic liver disease (SLD). This study examined the impact of long-term statin use on HCC risk in MASLD, compared to those without SLD. We used the Korean National Health Insurance database including 251,061 adults aged ≥40 years. Hepatic steatosis was defined using a fatty liver index cutoff of 30. Statin use was defined as cumulative prescribed days for four years, and participants were grouped by statin duration and MASLD status. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for HCC incidence from 2011 to 2019, during which 812 events occurred. Long-term statin use was associated with a reduced risk of HCC. Overall, the MASLD group exhibited a higher HCC risk compared to the non-SLD group. However, we found that the HCC risk in the MASLD group who used statins for more than 180 days was lower than that of the statin non-users without SLD (aHR, 0.64; 95% CI, 0.42-0.97). Statins showed a protective effect against HCC regardless of MASLD status, suggesting long-term statin use may mitigate the impact of hepatic steatosis on HCC development. Further clinical trials are needed to validate the effect of statin therapy in reducing HCC risk in patients with MASLD.

Endometrial cancer (EC) incidence continues to rise globally, driven mainly by obesity. Current diagnostic pathways rely on symptom presentation; no validated approach exists to identify asymptomatic individuals who may benefit from targeted prevention. The Progesterone Challenge Test (PCT) is a physiologic assessment of endometrial hormonal responsiveness that could pragmatically guide EC prevention interventions. The RESToRE study (NCT05651282) prospectively assessed the feasibility of the PCT as a community-based risk-stratification tool for EC prevention in British Columbia, Canada, between 2023 and 2024. Asymptomatic postmenopausal participants, defined by the absence of vaginal bleeding, with body mass index ≥34.9 kg/m² and an intact uterus, completed a 10-day course of oral medroxyprogesterone acetate (MPA) 10 mg daily. Feasibility, tolerability, and acceptability were evaluated. Of 96 eligible individuals, 68 enrolled, 53 initiated, and 51 completed the PCT. Sixteen participants experienced withdrawal bleeding (+PCT) (30.2% of those with evaluable results). All +PCT individuals were referred to a gynecologist for standard-of-care evaluation, including an endometrial biopsy. Among the 15 who underwent biopsy, 2 had a proliferative endometrium, and 1 had simple hyperplasia. Participants and providers found the test acceptable, citing its simplicity and low administrative burden. Side effects were mild (median severity ≤ 3/10), resulting in 3.8% (2/53) of participants discontinuing the MPA. The PCT was feasible, well-tolerated, and acceptable among higher-risk postmenopausal individuals, supporting its use as a physiologic, functional biomarker of endometrial responsiveness. These findings provide early evidence for a scalable, low-cost strategy to identify individuals likely to benefit from targeted EC prevention.