Translational cancer research · 2026
Association of serum vitamins and carotenoids with breast cancer status among adult women in NHANES 2017-2018: a cross-sectional study.
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Hu Bohan, Liang Ji
Аннотация
BACKGROUND: Breast cancer remains a major public health burden among women worldwide. Circulating vitamins and carotenoids may be related to oxidative stress, inflammation, and other biological processes relevant to breast cancer, but serum-based evidence remains inconsistent. The aim of this study is to examine the associations between serum vitamins and carotenoids and breast cancer status among women in National Health and Nutrition Examination Survey (NHANES) 2017-2018.
METHODS: This cross-sectional study included women aged ≥20 years from NHANES 2017-2018. Breast cancer status was defined by self- or proxy-reported physician diagnosis in the Medical Conditions Questionnaire. Men, women aged <20 years, participants with other cancers or unknown cancer status, and those with excessive missing data on key covariates were excluded. A total of 2,521 women were included, comprising 91 with breast cancer and 2,430 without breast cancer. Serum vitamin C was measured by ultra-performance liquid chromatography-electrochemical detection (UPLC-ECD), whereas retinol, tocopherols, and carotenoids were measured by high-performance liquid chromatography-photodiode array detection (HPLC-PDA). The analytes included vitamin C, retinol, α-tocopherol, γ-tocopherol, total lycopene, α-carotene, α-cryptoxanthin, β-cryptoxanthin, and lutein and zeaxanthin. Baseline characteristics were described using standardized mean differences (SMDs), and associations were evaluated using Firth penalized logistic regression with adjustment for demographic, socioeconomic, metabolic, lifestyle, reproductive, and gynecologic covariates. Restricted cubic spline and sensitivity analyses were performed. Machine learning models were further used to explore the joint discriminative patterns of these biomarkers and related covariates.
RESULTS: Compared with women without breast cancer, those with breast cancer were older [66.00 (11.73) vs. 49.42 (17.27) years; SMD =1.123], more likely to be widowed/divorced/separated (57.1% vs. 26.0%), non-Hispanic White (52.7% vs. 30.9%), hypertensive (60.4% vs. 38.8%), and hyperglycemic (56.0% vs. 42.2%). In the fully adjusted model, α-carotene, α-cryptoxanthin, β-cryptoxanthin, and lutein and zeaxanthin were inversely associated with breast cancer status. The most consistent association was observed for α-cryptoxanthin [Q2 vs. Q1: odds ratio (OR) =0.52, 95% confidence interval (CI): 0.30-0.89; Q3 vs. Q1: OR =0.38, 95% CI: 0.20-0.71; Q4 vs. Q1: OR =0.27, 95% CI: 0.12-0.56; P-trend <0.001]. Lutein and zeaxanthin were also inversely associated (Q3 vs. Q1: OR =0.39, 95% CI: 0.20-0.72; Q4 vs. Q1: OR =0.31, 95% CI: 0.15-0.60; P-trend <0.001). Restricted cubic spline analyses showed significant overall and nonlinear associations for α-cryptoxanthin (P-overall <0.001; P-nonlinear =0.005) and lutein and zeaxanthin (P-overall =0.002; P-nonlinear =0.03). Supplementary machine learning analyses also showed modest discriminative ability, with the best receiver operating characteristic-under the curve (ROC-AUC) of 0.824 (95% CI: 0.765-0.884).
CONCLUSIONS: Higher serum concentrations of α-cryptoxanthin, α-carotene, β-cryptoxanthin, and lutein and zeaxanthin were inversely associated with self-reported breast cancer status, with α-cryptoxanthin showing the most consistent association. Given the cross-sectional design and self-reported outcome, the findings should be interpreted cautiously.
METHODS: This cross-sectional study included women aged ≥20 years from NHANES 2017-2018. Breast cancer status was defined by self- or proxy-reported physician diagnosis in the Medical Conditions Questionnaire. Men, women aged <20 years, participants with other cancers or unknown cancer status, and those with excessive missing data on key covariates were excluded. A total of 2,521 women were included, comprising 91 with breast cancer and 2,430 without breast cancer. Serum vitamin C was measured by ultra-performance liquid chromatography-electrochemical detection (UPLC-ECD), whereas retinol, tocopherols, and carotenoids were measured by high-performance liquid chromatography-photodiode array detection (HPLC-PDA). The analytes included vitamin C, retinol, α-tocopherol, γ-tocopherol, total lycopene, α-carotene, α-cryptoxanthin, β-cryptoxanthin, and lutein and zeaxanthin. Baseline characteristics were described using standardized mean differences (SMDs), and associations were evaluated using Firth penalized logistic regression with adjustment for demographic, socioeconomic, metabolic, lifestyle, reproductive, and gynecologic covariates. Restricted cubic spline and sensitivity analyses were performed. Machine learning models were further used to explore the joint discriminative patterns of these biomarkers and related covariates.
RESULTS: Compared with women without breast cancer, those with breast cancer were older [66.00 (11.73) vs. 49.42 (17.27) years; SMD =1.123], more likely to be widowed/divorced/separated (57.1% vs. 26.0%), non-Hispanic White (52.7% vs. 30.9%), hypertensive (60.4% vs. 38.8%), and hyperglycemic (56.0% vs. 42.2%). In the fully adjusted model, α-carotene, α-cryptoxanthin, β-cryptoxanthin, and lutein and zeaxanthin were inversely associated with breast cancer status. The most consistent association was observed for α-cryptoxanthin [Q2 vs. Q1: odds ratio (OR) =0.52, 95% confidence interval (CI): 0.30-0.89; Q3 vs. Q1: OR =0.38, 95% CI: 0.20-0.71; Q4 vs. Q1: OR =0.27, 95% CI: 0.12-0.56; P-trend <0.001]. Lutein and zeaxanthin were also inversely associated (Q3 vs. Q1: OR =0.39, 95% CI: 0.20-0.72; Q4 vs. Q1: OR =0.31, 95% CI: 0.15-0.60; P-trend <0.001). Restricted cubic spline analyses showed significant overall and nonlinear associations for α-cryptoxanthin (P-overall <0.001; P-nonlinear =0.005) and lutein and zeaxanthin (P-overall =0.002; P-nonlinear =0.03). Supplementary machine learning analyses also showed modest discriminative ability, with the best receiver operating characteristic-under the curve (ROC-AUC) of 0.824 (95% CI: 0.765-0.884).
CONCLUSIONS: Higher serum concentrations of α-cryptoxanthin, α-carotene, β-cryptoxanthin, and lutein and zeaxanthin were inversely associated with self-reported breast cancer status, with α-cryptoxanthin showing the most consistent association. Given the cross-sectional design and self-reported outcome, the findings should be interpreted cautiously.