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Gene‐diet‐interactions in folate‐mediated one‐carbon metabolism modify colon cancer risk
Author(s) -
Liu Amy Y.,
Scherer Dominique,
Poole Elizabeth,
Potter John D.,
Curtin Karen,
Makar Karen,
Slattery Martha L.,
Caan Bette J.,
Ulrich Cornelia M.
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200180
Subject(s) - mtrr , methylenetetrahydrofolate reductase , vitamin b12 , colorectal cancer , biology , medicine , methionine , endocrinology , genetics , allele , physiology , carcinogenesis , gene , cancer , amino acid
Scope The importance of folate‐mediated one‐carbon metabolism ( FOCM ) in colorectal carcinogenesis is emphasized by observations that high dietary folate intake is associated with decreased risk of colon cancer ( CC ) and its precursors. Additionally, polymorphisms in FOCM ‐related genes have been repeatedly associated with risk, supporting a causal relationship between folate and colorectal carcinogenesis. Methods and results We investigated ten candidate polymorphisms with defined or probable functional impact in eight FOCM ‐related genes ( SHMT 1, DHFR , DNMT 1, MTHFD 1, MTHFR , MTRR , TCN 2, and TDG ) in 1609 CC cases and 1974 controls for association with CC risk and for interaction with dietary factors. No polymorphism was statistically significantly associated with overall risk of CC . However, statistically significant interactions modifying CC risk were observed for DNMT 1 I311V with dietary folate, methionine, vitamin B 2 , and vitamin B 12 intake and for MTRR I22 M with dietary folate, a predefined one‐carbon dietary pattern, and vitamin B 6 intake. We observed statistically significant gene‐diet interactions with five additional polymorphisms. Conclusion Our results provide evidence that FOCM ‐related dietary intakes modify the association between CC risk and FOCM allelic variants. These findings add to observations showing that folate‐related gene‐nutrient interactions play an important role in modifying the risk of CC .