The Association Between Vitamin C and Cancer: A Two-Sample Mendelian Randomization Study

Area of Science:

• Nutritional Epidemiology
• Genetic Epidemiology
• Oncology

Background:

• Observational studies suggest a potential inverse association between vitamin C intake and cancer risk, but evidence remains inconclusive.
• The causal relationship between vitamin C and cancer risk requires robust investigation due to conflicting findings.

Purpose of the Study:

• To investigate the causal effect of genetically predicted vitamin C levels on the risk of overall and specific cancer types.
• To leverage Mendelian randomization to overcome confounding factors present in observational studies.

Main Methods:

• A two-sample Mendelian randomization study was conducted using genome-wide association study data.
• Single-nucleotide polymorphisms (SNPs) strongly associated with vitamin C levels were identified from a large meta-analysis (n=52,018).
• Inverse-variance weighted (IVW), weighted median, and MR-Egger methods were employed for causal inference, with sensitivity analyses for heterogeneity and pleiotropy.

Main Results:

• The primary analysis using the IVW method did not support a causal association between genetically predicted vitamin C and the risk of overall cancer.
• No significant causal links were found for 14 specific cancer types.
• Sensitivity analyses using weighted median and MR-Egger methods corroborated the main findings, with no evidence of significant heterogeneity or pleiotropy.

Conclusions:

• Genetically predicted vitamin C levels are not causally associated with the risk of developing cancer.
• The findings challenge the hypothesis that higher vitamin C levels inherently reduce cancer risk.
• Further research is essential to elucidate the complex role of vitamin C in cancer, including potential therapeutic applications and underlying biological mechanisms.