Associations between dietary intake of zinc and selenium and breast cancer: findings from a NHANES cross-sectional study

zinc and selenium are essential trace elements that have been suggested to influence cancer development, but their relationship with breast cancer remains unclear. Additionally, biomarkers such as bilirubin, uric acid, and gamma glutamyl transferase (GGT) are associated with various metabolic processes that could affect cancer progression. This research aimed to examine the associations between zinc and selenium levels and breast cancer, and the extent to which bilirubin, uric acid and GGT mediate the effect on breast cancer. In all, 25,244 females were enrolled from the 1999-2020 National Health and Nutrition Examination Survey (NHANES). The associations between zinc and selenium intake and prevalent breast cancer were explored through meticulous adjustments for covariates utilizing both multivariate and stratified logistic regression analyses. Furthermore, the mediation and interaction effects were performed by mediation analyses and generalized linear model. Prevalent breast cancer was associated with race, marital status and age. Additionally, participants with breast cancer showed lower zinc (10.2 vs. 12.0 mg, P=0.001) and selenium levels (95.7 vs. 114.4 µg, P<0.001) and higher incidence of diabetes (2.60% vs. 97.40%, P<0.001) and cardiovascular disease (CVD) (3.07% vs. 96.93%, P<0.001) comorbidities than the control group. Logistic regression analysis showed a strong linear protective association between zinc and selenium levels and breast cancer. After further adjustment in Model 3, statistical significance remained for each unit increase in selenium [odds ratio (OR), 0.66; 95% confidence interval (CI): 0.47-0.93; P=0.02], as well as for Q4 versus Q1 for zinc (OR, 0.48; 95% CI: 0.27-0.86; P=0.01). In addition, a significant age-effect modification was observed for zinc (Pinteraction=0.07) associations were stronger in women aged over 40 years compared to younger women. Finally, bilirubin potentially mediated the protective association between zinc and breast cancer, while bilirubin, uric acid, and GGT levels mediated approximately 10% of the relationship between selenium and breast cancer. Our study highlighted negative correlations between zinc and selenium intake and breast cancer in women. The mediation analysis has shown that bilirubin, uric acid and GGT play an indirect role.