Effect of zinc and selenium on breast cancer risk: a NHANES cross-sectional study and mediation analysis

Abstract

Abstract Background: This research aimed to examine the correlation between blood zinc and selenium levels and the occurrence of breast cancer, and the extent to which bilirubin, uric acid and γ-glutamyl transferase (GGT)mediate the effect on breast cancer. Methods: In all, 25,244 adults were enrolled from the 1990-2020 Nutrition Examination Survey (NHANES). The outcome was considered as the occurrence of breast cancer in this study. Zinc and selenium levels were categorized into quartiles (Q1-Q4), and the correlation between zinc or selenium intake and breast cancer incidence was 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. Results: The incidence of breast cancer was associated with race, marital status and age. Besides, participants with breast cancer showed lower zinc (10.2 vs 12.0 mg/ml, p=0.001) and selenium levels (95 vs 114 μg/ml, p<0.001) and higher incidence of diabetes (15% vs 8.5%, p<0.001) and cardiovascular disease (CVD) (16% vs 7.4%, 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. Moreover, this association changed slightly after adjusting demographic characteristics, socioeconomic characteristics, health factors, and comorbidities and remained statistically significant. In addition, no interaction was found between diabetes and CVD and the effect of zinc/selenium intake on breast cancer risk (p for interaction > 0.05). Finally, bilirubin potentially mediated the protective association between zinc and breast cancer risk, while bilirubin, uric acid, and GGT levels mediated approximately 10% of the relationship between selenium and breast cancer. Conclusion: Our study highlighted a negative linear association between blood zinc and selenium concentrations and the risk of breast cancer in women. The mediation analysis has shown that bilirubin, uric acid and GGT play an indirect role.