Abstract 6231: Associations of serum concentrations of α- and γ-tocopherols with cancer mortality

Background: While tocopherols’ antioxidant and anti-inflammatory properties suggest their potential anti-cancer effects, little is known about the association between circulating tocopherols and mortality outcomes, particularly among cancer survivors. This study aimed to evaluate whether serum concentrations of α- and γ-tocopherols were associated with the risk of death from all causes, cancer, and cardiovascular disease (CVD). Methods: We incorporated 16,696 US adults aged ≥20 (1,466 cancer survivors and 15,230 cancer-free individuals) from the National Health and Nutrition Examination Survey, 1999-2006. Serum α- and γ-tocopherols were quantified by high-performance liquid chromatography and categorized into quartiles. Mortality and cause of death were ascertained by linkage to National Death Index records through December 31, 2019 (median follow-up of 16.1 years). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for all-cause, cancer, and CVD mortality after adjustment for comprehensive covariates, including serum cholesterol levels, sociodemographics, lifestyle (e.g., diet, physical activity), and comorbidities. Restricted cubic splines were used to evaluate the potential non-linearity of the associations. Results: Cancer survivors in the highest quartile of serum α-tocopherol demonstrated a 50% lower risk of cancer mortality compared to those in the lowest quartile (HR=0.50, 95% CI:0.32-0.80, p-trend=0.009). Similar protective associations were observed in cancer-free individuals, with those in the highest quartile of serum α-tocopherol showing a 31% reduction in cancer mortality risk (HR=0.69, 95% CI: 0.46-1.02, p-trend=0.05). The association between α-tocopherol and cancer mortality was non-linear (p<0.001), exhibiting the strongest protective effects at concentrations ranging from 35 μmol/L to 50 μmol/L. All-cause mortality risk was also lower among those with higher α-tocopherol in cancer survivors (HR=0.75, 95% CI: 0.54-1.03, p-trend=0.02) and cancer-free individuals (HR=0.86, 95% CI: 0.74-1.00, p-trend=0.03). No significant associations were found for γ-tocopherols. Conclusions: In this nationally representative sample of US adults, higher circulating concentrations of α-tocopherol were associated with a reduced risk of cancer mortality among both cancer survivors and cancer-free individuals. Our findings indicate the potential health benefits of circulating α-tocopherol in reducing preventable deaths and provide population-based evidence for the role of α-tocopherol in cancer survivorship care. Citation Format: Yoo-Min Koh, Jae Jeong Yang, Young-Rock Hong, Shama Karanth, Dejana Braithwaite, Hyung-Suk Yoon. Associations of serum concentrations of α- and γ-tocopherols with cancer mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6231.