AUTHOR=Zhu Jiahao , Lian Jie , Wang Xin , Wang Ren , Pang Xiangyi , Xu Benjie , Wang Xing , Li Chenyang , Ji Shengjun , Lu Haibo 

TITLE=Role of endogenous and exogenous antioxidants in risk of six cancers: evidence from the Mendelian randomization study

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1185850

DOI=10.3389/fphar.2023.1185850

ISSN=1663-9812

ABSTRACT=Although oxidative stress is known to contribute to cancer, and endogenous and exogenous antioxidants are thought to prevent tumorigenesis by suppressing oxidative stress-induced DNA damage, antioxidants have also been reported to show negative effects on tumor formation, necessitating characterization of the causal associations between antioxidants and cancer risk.In this study, Mendelian randomization (MR) analysis, primarily inverse-variance weighted MR, was used to assess the causal effect of six endogenous and five exogenous diet-derived antioxidants on the risk of six cancers. MR-Egger intercept test and Cochran's Q statistic were utilized to assess pleiotropy and heterogeneity, respectively. For endogenous antioxidants, a bidirectional two-sample MR analysis was conducted. Our findings suggested that serum albumin has a negative causal association with the risk of prostate cancer (odds ratio [OR]=0.78, 95% confidence interval [CI]: 0.68-0.91, P=0.001). The risks of the six cancers showed no significant associations with endogenous antioxidants in the converse MR analysis. For exogenous antioxidants, the unidirectional two-sample MR analysis exhibited a nominal relationship between the serum retinol level and non-small-cell lung cancer risk (OR=0.29, 95% CI: 0.11-0.76, P=0.011). Thus, our study revealed the protective effects of genetic susceptibility to high circulating albumin levels on prostate cancer, providing potential targeted interventions for prostate cancer prevention.