Platelet-to-high-density lipoprotein ratio (PHR) as a predictive biomarker for gastrointestinal cancers: evidence from NHANES.

Background: Gastrointestinal (GI) cancers, including gastric, colorectal, and esophageal cancers, pose a significant global health burden. Despite advancements in diagnostic tools, early detection remains challenging, particularly in low-resource settings. Emerging evidence highlights the platelet-to-high-density lipoprotein ratio (PHR) as a novel biomarker integrating systemic inflammation and lipid metabolism. However, its association with GI cancer risk remains underexplored.

Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2010 to 2018, comprising 19,388 participants, including 230 with GI cancers. PHR was calculated as the ratio of platelet count to high-density lipoprotein cholesterol levels and categorized into quartiles. Weighted logistic regression models, restricted cubic spline analysis, and subgroup analyses were employed to evaluate the association between PHR and GI cancer risk, adjusting for demographic, socioeconomic, lifestyle, and clinical factors.

Results: Elevated PHR was independently associated with an increased risk of GI cancers. Participants in the highest PHR quartile exhibited a significantly higher risk (adjusted OR = 3.09; 95% CI: 2.16-4.43) compared to the lowest quartile. A dose-response relationship was observed, with two critical inflection points at PHR values of 3.2 and 4.5. Subgroup analyses revealed stronger associations among older adults, males, and obese individuals. The findings suggest that PHR may reflect the dynamic balance of systemic inflammation and lipid metabolism, contributing to tumorigenesis.

Conclusion: This study identifies PHR as a promising, cost-effective biomarker for early detection and risk stratification of GI cancers. Its integration into screening programs could improve precision medicine strategies by identifying high-risk individuals for early intervention. Further longitudinal and mechanistic studies are warranted to confirm these findings and explore the underlying biological mechanisms.