Epigenetic clocks can quantify DNA methylation by measuring the methylation levels at specific sites in the genome, which correlate with biological age (BA). Accelerated aging, where BA exceeds chronologic age, has been studied in relation to cancer development, but its utility in cancer prevention remains unclear. Accelerated aging holds promise as a tool to explain the increase in early-onset colorectal cancer (EOCRC). We investigate the association of accelerated aging and the presence of preneoplastic polyps (PNP) in the colon, defined as tubular adenomas and sessile serrated adenomas. In this study of persons under age 50 undergoing colonoscopy, we used peripheral blood samples to determine BA and age acceleration metrics. Age acceleration was determined by interrogating DNA methylation at specific CpG sites across the genome, which has been shown to correlate with age. We then conducted logistic regression analyses to evaluate the association between age acceleration and PNPs. In total, 51 patient samples were evaluated. We found that that the odds of harboring a PNP are 16% higher with 1 year of accelerated aging, as measured by GrimAge. However, the strongest risk factor for PNPs remained male sex. This represents one of the first studies to explore accelerated aging and PNP in patients under the age of 50. A risk-stratified approach to EOCRC screening would minimize unnecessary colonoscopies and minimize healthcare burden while addressing the increase in EOCRC. Our findings suggest that BA calculations with peripheral blood collections could be an important component of such a risk model. Prevention Relevance: Understanding the association of accelerated aging and colorectal PNPs presents an opportunity to develop a risk-stratified approach to colorectal cancer screening in young persons.

Background: The sensitivity of ultrasound plus alpha-fetoprotein (AFP) for early-stage hepatocellular carcinoma (HCC) detection remains suboptimal, prompting interest in blood-based biomarkers as an alternative strategy. The ASAP [age, sex, AFP, PIVKA-II] score has promising performance, although validation in contemporary Western populations is needed. Methods: We conducted a case–control study in which the cases were patients with HCC and the controls had cirrhosis without HCC. AFP, PIVKA-II, LG2m, and GP73 were measured using the Abbott Alinity platform, and ASAP scores were calculated. Sensitivity and specificity for early-stage HCC (BCLC stage 0/A) were compared between ASAP and ultrasound plus AFP using McNemar’s chi-square test. Results: Among 294 patients (median age of 61 years, 67.7% men), 50.7% had HCC (69.1% BCLC 0/A), and 49.3% had cirrhosis. The performance of individual biomarkers for early-stage HCC was moderate to poor (AUROC: AFP 0.71, PIVKA-II 0.73, LG2m 0.51, and GP73 0.53). ASAP, at a cutoff of ≥0.526, demonstrated a sensitivity of 88.3% for early-stage HCC, with specificity of 54.5%. Sensitivity was higher in men and viremic HCV, whereas specificity was higher in younger individuals, women, and Child–Pugh A cirrhosis. In subgroup analysis (n = 178), ASAP had comparable sensitivity to ultrasound plus AFP (85.5% vs. 90.3%; p = 0.51) but lower specificity (53.4% vs. 93.1%; p < 0.001). Using the Youden-optimized cutoff (≥0.804) improved specificity to 83.4% while maintaining a sensitivity of 68.0% for early-stage HCC. Conclusions: ASAP demonstrated high sensitivity for early-stage HCC detection but low specificity. These findings suggest a need for optimized cutoffs prior to implementation in clinical practice.

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.