A groundbreaking study published in BMC Cancer has uncovered a compelling link between increased skin autofluorescence (SAF) and the future development of cancer, offering promising new avenues for early detection and risk stratification. This research harnesses advanced AGE (advanced glycation end-product) reader technology to non-invasively measure tissue glycation, a biochemical process long implicated in aging and metabolic disorders. The findings not only reinforce the utility of SAF in predicting diabetes and cardiovascular disease but also position it as a potential biomarker for oncological risk, broadening the horizons of preventive medicine.
Skin autofluorescence is essentially a proxy for the accumulation of AGEs, compounds formed through a non-enzymatic reaction between sugars and proteins or lipids. These AGEs alter tissue structure and cellular function, promoting inflammation and oxidative stress. While the relationship between AGEs and chronic diseases like type 2 diabetes (T2D) and cardiovascular disease (CVD) has been extensively documented, their involvement in carcinogenesis remains an emergent field of inquiry. This study, led by Boersma et al., systematically explores whether elevated SAF correlates with an increased incidence of cancer over a long-term follow-up.
The Lifelines Cohort Study, a large population-based cohort from the Northern Netherlands, served as the fertile ground for this investigation. The study’s expansive design involved nearly 78,000 participants, who were initially screened between 2006 and 2013 and followed for a median duration of 11.5 years. Importantly, all participants were cancer-free at baseline, thereby allowing the researchers to assess new cancer development prospectively. Additionally, a subgroup of participants diagnosed with T2D was included to provide insight into whether pre-existing metabolic dysfunction alters the SAF-cancer association.
During the observational period, the incidence of cancer varied markedly among different groups. Among participants without diabetes, cumulative cancer rates reached 10.7% in males and 12.5% in females. In contrast, those living with T2D evidenced significantly higher cancer incidences—23.6% in males and 20.2% in females—consistent with earlier evidence that diabetes confers an elevated risk for several malignancies. However, what distinguishes this research is its focus on SAF as a predictive metric, independent of traditional risk factors.
Cox proportional hazards models revealed a robust association between SAF levels and subsequent cancer diagnosis. Unadjusted analyses showed that higher SAF predicted more than double the hazard of cancer development across the entire cohort, with a hazard ratio (HR) of approximately 2.36. Notably, this relationship was more pronounced in men, who exhibited a hazard ratio exceeding 3.0. Even after rigorous adjustments for confounders—such as age, sex, body mass index, waist circumference, smoking history quantified in pack-years, presence of diabetes, and metabolic syndrome—the link between increased SAF and cancer risk persisted, albeit with a more modest HR of 1.11.
Such resilience of the SAF association following multifaceted adjustments underscores its potential as an independent biomarker for cancer risk. Sensitivity analyses excluding skin cancers and cancers diagnosed within two years of baseline further strengthened the findings, indicating that heightened SAF precedes cancer onset rather than reflecting existing disease. These analytical layers cumulatively suggest that SAF measurement might provide clinicians with a non-invasive window into patients’ oncogenic milieu well before malignancy manifests clinically.
The study also disentangled cancer type-specific relationships with SAF. Particularly, cancers of the lung, oesophagus, and urinary tract demonstrated the strongest associations, all achieving high statistical significance. Other malignancies, including ovarian, female genital tract, and liver cancer, yielded suggestive but less potent correlations. This site-specific pattern potentially reflects differential AGE accumulation or diverse tissue susceptibilities, inviting further exploration into organ-specific pathophysiological pathways linking glycation to carcinogenesis.
When focusing on participants with type 2 diabetes, elevated SAF similarly correlated with increased cancer risk in unadjusted models. Nevertheless, this association lost statistical significance once age and sex were accounted for, and notably after full adjustment for confounders, indicating a more complex interplay in this subgroup. It is plausible that diabetes-linked metabolic derangements overshadow the predictive value of SAF in these patients, or that SAF simply reflects a convergence of risk factors rather than exerting an independent effect.
Mechanistically, the connection between AGEs, reflected via SAF, and cancer development may center on the chronic pro-inflammatory state induced by AGE accumulation. AGEs can crosslink extracellular matrix proteins, impair cellular repair mechanisms, and activate receptors such as RAGE (receptor for advanced glycation end-products), triggering intracellular signaling cascades that promote tumorigenesis. Moreover, oxidative stress fueled by AGEs may induce DNA damage, genomic instability, and dysregulated cell proliferation, all hallmarks of cancer biology.
From a clinical standpoint, the emergence of SAF as a potential biomarker heralds significant innovation in oncology screening protocols. Unlike invasive tissue biopsies or expensive imaging studies, SAF measurement uses non-ionizing technology and can be performed swiftly in outpatient settings. If future validations corroborate these findings, SAF could be integrated into risk prediction algorithms, particularly among populations at heightened risk due to metabolic disorders or age, enabling targeted surveillance and early interventions.
Nonetheless, several questions remain before SAF can be adopted in oncologic practice. The current study, though robust, is observational and cannot definitively establish causality. Additionally, the moderate hazard ratios post-adjustment signal that SAF alone might best be used as part of a multimodal risk assessment rather than a standalone predictor. Moreover, elucidating the biological mechanisms that underpin SAF’s association with specific cancer types will be critical to developing tailored preventive strategies.
Importantly, the study leveraged comprehensive pathology data from the Dutch Nationwide Pathology Databank (PALGA) to accurately classify incident cancers, enhancing the reliability of outcome ascertainment. This data linkage, combined with an extensive follow-up period, strengthens the evidence base for SAF’s predictive value. The study’s geographical and demographic context—predominantly Northern European populations—also warrants further research in more ethnically and environmentally diverse cohorts to evaluate generalizability.
In summary, this pioneering investigation by Boersma and colleagues positions skin autofluorescence as a promising, non-invasive biomarker related to future cancer risk across a broad population. While SAF is already established in monitoring diabetes and cardiovascular disease risk, its extension into oncology heralds a new frontier linking metabolic health to malignancy prediction. As science advances towards precision medicine, tools like SAF measurement may empower clinicians to identify at-risk individuals earlier and tailor prevention strategies more effectively.
Future research directions include prospective interventional studies to determine whether reducing AGE accumulation can mitigate cancer risk, and whether SAF-guided screening translates into improved clinical outcomes. Additionally, integrating SAF with genomic, proteomic, and metabolomic data could refine risk stratification models, uncover mechanistic insights, and reveal novel therapeutic targets. These efforts will be essential to fully harness the potential of SAF in the fight against cancer.
The revelation that a simple measure of skin fluorescence can forecast complex disease states long before clinical symptoms arise exemplifies the transformative power of biomarker science. As this field matures, widespread SAF screening could become routine, reshaping how medicine anticipates and intercepts cancer development at its earliest phases.
Subject of Research: The association between skin autofluorescence (SAF)—a marker of advanced glycation end-product accumulation—and future cancer risk in a large population-based cohort.
Article Title: Increased skin autofluorescence predicts future cancer development
Article References:
Boersma, H.E., Sidorenkov, G., Smit, A.J. et al. Increased skin autofluorescence predicts future cancer development. BMC Cancer 25, 1375 (2025). https://doi.org/10.1186/s12885-025-14801-w
Image Credits: Scienmag.com
