Cancer
Associations of lipid peroxidation biomarkers with renal cell carcinoma and interactions with metals and micronutrients Wei-Jen Chen* Wei-Jen Chen Chen Chen Chen Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan
Oxidative stress is a key biological mechanism linking environmental exposures to renal cell carcinoma (RCC). Experimental evidence suggests that increased lipid peroxidation in renal proximal tubules contributes to renal carcinogenesis. Given that 8-isoprostaglandin-F2α (8-iso-PGF2α), a reliable biomarker of lipid peroxidation, has been associated with kidney failure, we aimed to investigate the associations of lipid peroxidation biomarkers with RCC and their interactions with metal exposure and micronutrients.
We conducted a clinic-based case-control study of 204 incident RCC cases and 628 matched non-cancer controls in Taipei City, Taiwan. At enrollment, blood cadmium and lead and plasma selenium, folate, and vitamin B12 were quantified. Urinary lipid peroxidation biomarkers [8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and prostaglandin-F2α (PGF2α)] were measured, and 8-iso-PGF2α fractions from chemical (aCLP) and enzymatic (aPGHS) pathways were characterized. Multivariable logistic regression examined associations of each metal, micronutrient, and lipid peroxidation biomarker with RCC. Combined effects of exposures (metals or micronutrients) and lipid peroxidation biomarkers on RCC were evaluated on additive and multiplicative scales.
All lipid peroxidation biomarkers were positively associated with RCC. Compared with participants with low cadmium/low 8-iso-PGF2α (or aCLP), the OR for RCC was elevated among those with high cadmium/high 8-iso-PGF2α (or aCLP), with positive interaction on both additive and multiplicative scales. For micronutrients, the OR for RCC was also elevated among participants with low plasma folate and high aCLP, with evidence of a positive interaction. No interactions were identified for lead, selenium, and vitamin B12 with lipid peroxidation biomarkers.
Our study provides evidence of the combined effects of selected metals/micronutrients and lipid peroxidation on RCC, providing insights into potential mechanisms underlying environmentally related RCC.
