TY - JOUR
T1 - Circulating Phylloquinone and the Risk of Four Female-Specific Cancers
T2 - A Mendelian Randomization Study
AU - Yalew, Melaku
AU - Mulugeta, Anwar
AU - Lumsden, Amanda L.
AU - Madakkatel, Iqbal
AU - Lee, S. Hong
AU - Oehler, Martin K.
AU - Mäenpää, Johanna
AU - Hyppönen, Elina
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/11
Y1 - 2024/11
N2 - Background: Observational studies have linked vitamin K and cancer, but the causality of this association remains unknown. This Mendelian randomization (MR) study aims to investigate the association between circulating phylloquinone (vitamin K1) levels and four female-specific cancers. Methods: We used four single-nucleotide polymorphisms (SNPs) to instrument phylloquinone, with the reported F-statistic 16.00–28.44 for all variants. SNP–outcome associations were obtained from consortia meta-analyses, UK Biobank, and the FinnGen database (up to 145,257/419,675, 27,446/362,324, 15,181/591,477, and 2211/320,454 cases/controls for breast, ovarian, endometrial, and cervical cancer, respectively). Analyses were conducted using five complementary MR methods including pleiotropy robust approaches. The MR Egger intercept test, MR PRESSO global test and leave-one-out analyses were used to test for and identify pleiotropic variants. Results: The relevance of the instrument was validated by positive control analyses on coagulation factor IX (p = 0.01). However, the main MR analysis and all sensitivity analyses were consistently supportive of a null association between phylloquinone and all four cancers (p > 0.05 for all analyses, across all methods). MR-PRESSO did not detect outlying variants, and there was no evidence of horizontal pleiotropy relating to any cancer outcome (pintercept > 0.26 for all). Conclusions: We found no evidence for an association between genetically predicted circulating phylloquinone levels and the risk of four female-specific cancers.
AB - Background: Observational studies have linked vitamin K and cancer, but the causality of this association remains unknown. This Mendelian randomization (MR) study aims to investigate the association between circulating phylloquinone (vitamin K1) levels and four female-specific cancers. Methods: We used four single-nucleotide polymorphisms (SNPs) to instrument phylloquinone, with the reported F-statistic 16.00–28.44 for all variants. SNP–outcome associations were obtained from consortia meta-analyses, UK Biobank, and the FinnGen database (up to 145,257/419,675, 27,446/362,324, 15,181/591,477, and 2211/320,454 cases/controls for breast, ovarian, endometrial, and cervical cancer, respectively). Analyses were conducted using five complementary MR methods including pleiotropy robust approaches. The MR Egger intercept test, MR PRESSO global test and leave-one-out analyses were used to test for and identify pleiotropic variants. Results: The relevance of the instrument was validated by positive control analyses on coagulation factor IX (p = 0.01). However, the main MR analysis and all sensitivity analyses were consistently supportive of a null association between phylloquinone and all four cancers (p > 0.05 for all analyses, across all methods). MR-PRESSO did not detect outlying variants, and there was no evidence of horizontal pleiotropy relating to any cancer outcome (pintercept > 0.26 for all). Conclusions: We found no evidence for an association between genetically predicted circulating phylloquinone levels and the risk of four female-specific cancers.
KW - circulating phylloquinone
KW - female-specific cancers
KW - Mendelian randomization
KW - vitamin K
UR - http://www.scopus.com/inward/record.url?scp=85208445635&partnerID=8YFLogxK
U2 - 10.3390/nu16213680
DO - 10.3390/nu16213680
M3 - Article
AN - SCOPUS:85208445635
SN - 2072-6643
VL - 16
JO - Nutrients
JF - Nutrients
IS - 21
M1 - 3680
ER -