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 (SHMT1, DHFR, DNMT1, MTHFD1, MTHFR, MTRR, TCN2, 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 DNMT1 I311V with dietary folate, methionine, vitamin B2 , and vitamin B12 intake and for MTRR I22M with dietary folate, a predefined one-carbon dietary pattern, and vitamin B6 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.
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 (SHMT1, DHFR, DNMT1, MTHFD1, MTHFR, MTRR, TCN2, 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 DNMT1 I311V with dietary folate, methionine, vitamin B2 , and vitamin B12 intake and for MTRRI22M with dietary folate, a predefined one-carbon dietary pattern, and vitamin B6 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.
Authors: E Kampman; M L Slattery; J Bigler; M Leppert; W Samowitz; B J Caan; J D Potter Journal: Cancer Epidemiol Biomarkers Prev Date: 1999-01 Impact factor: 4.254
Authors: C M Ulrich; E Kampman; J Bigler; S M Schwartz; C Chen; R Bostick; L Fosdick; S A Beresford; Y Yasui; J D Potter Journal: Cancer Epidemiol Biomarkers Prev Date: 1999-08 Impact factor: 4.254
Authors: N M van der Put; F Gabreëls; E M Stevens; J A Smeitink; F J Trijbels; T K Eskes; L P van den Heuvel; H J Blom Journal: Am J Hum Genet Date: 1998-05 Impact factor: 11.025
Authors: K Liu; M Slattery; D Jacobs; G Cutter; A McDonald; L Van Horn; J E Hilner; B Caan; C Bragg; A Dyer Journal: Ethn Dis Date: 1994 Impact factor: 1.847
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Authors: Aneliya Velkova; Jennifer E L Diaz; Faith Pangilinan; Anne M Molloy; James L Mills; Barry Shane; Erica Sanchez; Conal Cunningham; Helene McNulty; Cheryl D Cropp; Joan E Bailey-Wilson; Alexander F Wilson; Lawrence C Brody Journal: Hum Mol Genet Date: 2017-12-15 Impact factor: 6.150
Authors: Jun Wang; Isaac Asante; John A Baron; Jane C Figueiredo; Robert Haile; A Joan Levine; Polly A Newcomb; Allyson S Templeton; Fredrick R Schumacher; Stan G Louie; Graham Casey; David V Conti Journal: Genet Epidemiol Date: 2019-09-10 Impact factor: 2.135