Folate Intake and Risk of Urothelial Carcinoma: A Systematic Review and Meta-Analysis of Epidemiological Studies

Abstract

We aimed to investigate the association between folate intake and the risk of urothelial carcinoma (UC). A systematic literature search using Pubmed and EMBASE databases was performed to find prospective cohort studies, population-based case-control study or hospital-based case-control study investigating the association of folate intake and the risk of UC. A total of 19 studies involving 11,175 cases and 656,161 individuals were included. High intake of folate was associated with a decreased risk of UC, with a pooled OR of 0.78 (95% CI: 0.66–0.93, P = 0.006) for the highest category of intake vs. the lowest. The data suggested that folate may contribute to the prevention of urothelial cancer. However, the association was observed only in case-control studies (OR = 0.56, 95% CI: 0.39–0.79, P = 0.001), but not in cohort studies (RR = 0.97, 95% CI: 0.87–1.09, P = 0.638). Dose-response meta-analysis showed that an increment of folate intake (100 μg/day) corresponded to an 8% deceased risk of invasive UC (RR = 0.92, 95% CI: 0.87–0.98, P = 0.004). High folate intake might be inversely associated with risk of UC particularly invasive UC, which needs to be confirmed.

Acknowledgments

We thank Editage of Cactus Communications for the English language editing of the article.

Disclosure Statement

The authors declare that they have no conflict of interest.

Data Availability Statement

Not applicable.

Consent to Participate

Not required.

Ethics Approval

Not required.

Code Availability

STATA version 14.0 (Stata Corp, College Station, TX, USA).

Author’s Contributions

Yi Gu and Jie Zeng equally contributed to the conception and design of the research; Yixin Zou and Chang Liu contributed to the acquisition and analysis of the data; Yi Gu, Jie Zeng, Yixin Zou and Hongjuan Fu contributed to the interpretation of the data; and Yi Gu and Jie Zeng drafted the manuscript. All authors critically revised the manuscript, agree to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the final manuscript.

Additional information

Funding

This study was supported by Postgraduate mentor team-building program of Southwest University (XYDS201905).