Circulating Phylloquinone and the Risk of Four Female-Specific Cancers: A Mendelian Randomization Study

Area of Science:

• Nutritional Epidemiology
• Genetic Epidemiology
• Oncology

Background:

• Observational studies suggest a link between vitamin K and cancer.
• Causality of this association requires further investigation.
• This study focuses on phylloquinone (vitamin K1) and female-specific cancers.

Purpose of the Study:

• To investigate the causal association between circulating phylloquinone levels and four female-specific cancers using Mendelian randomization.
• To determine if genetically predicted vitamin K1 levels influence the risk of breast, ovarian, endometrial, and cervical cancer.

Main Methods:

• Utilized four single-nucleotide polymorphisms (SNPs) as genetic instruments for phylloquinone.
• Employed large-scale datasets from consortia meta-analyses, UK Biobank, and FinnGen.
• Applied five complementary Mendelian randomization methods, including pleiotropy-robust approaches, with sensitivity analyses.

Main Results:

• Instrument relevance was confirmed via positive control analysis for coagulation factor IX.
• Main and sensitivity analyses consistently showed a null association between phylloquinone and the four cancers.
• No evidence of pleiotropy or outlying variants was detected, strengthening the null findings.

Conclusions:

• Genetically predicted circulating phylloquinone levels are not associated with the risk of breast, ovarian, endometrial, or cervical cancer.
• The study provides robust evidence against a causal role of vitamin K1 in these female cancers.
• Findings contribute to understanding the relationship between vitamin K status and cancer risk.