PMID- 17449906
OWN - NLM
STAT- MEDLINE
DCOM- 20071019
LR  - 20191210
IS  - 0143-3334 (Print)
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 28
IP  - 8
DP  - 2007 Aug
TI  - Genetic polymorphisms in one-carbon metabolism: associations with CpG island 
      methylator phenotype (CIMP) in colon cancer and the modifying effects of diet.
PG  - 1672-9
AB  - This study investigated associations between CpG island methylator phenotype 
      (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism 
      and thus, potentially the provision of methyl groups and risk of colon cancer. 
      Data from a large, population-based case-control study (916 incident colon cancer 
      cases and 1,972 matched controls) were used. Candidate polymorphisms in 
      methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), 
      transcobalamin II (TCNII), methionine synthase (MTR), reduced folate carrier 
      (RFC), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate 
      reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated. CIMP- or 
      CIMP+ phenotype was based on five CpG island markers: MINT1, MINT2, MINT31, p16 
      and MLH1. The influence of specific dietary factors (folate, methionine, vitamin 
      B(12) and alcohol) on these associations was also analyzed. We hypothesized that 
      polymorphisms involved in the provision of methyl groups would be associated with 
      CIMP+ tumors (two or more of five markers methylated), potentially modified by 
      diet. Few associations specific to CIMP+ tumors were observed overall, which does 
      not support the hypothesis that the provision of methyl groups is important in 
      defining a methylator phenotype. However, our data suggest that genetic 
      polymorphisms in MTHFR 1,298A > C, interacting with diet, may be involved in the 
      development of highly CpG-methylated colon cancers. AC and CC genotypes in 
      conjunction with a high-risk dietary pattern (low folate and methionine intake 
      and high alcohol use) were associated with CIMP+ (OR = 2.1, 95% CI = 1.3-3.4 
      versus AA/high risk; P-interaction = 0.03). These results provide only limited 
      support for a role of polymorphisms in one-carbon metabolism in the etiology of 
      CIMP colon cancer.
FAU - Curtin, Karen
AU  - Curtin K
AD  - Department of Internal Medicine, University of Utah Health Sciences Center, 375 
      Chipeta Way, Suite A, Salt Lake City, UT 84108, USA. karen.curtin@hsc.utah.edu
FAU - Slattery, Martha L
AU  - Slattery ML
FAU - Ulrich, Cornelia M
AU  - Ulrich CM
FAU - Bigler, Jeannette
AU  - Bigler J
FAU - Levin, Theodore R
AU  - Levin TR
FAU - Wolff, Roger K
AU  - Wolff RK
FAU - Albertsen, Hans
AU  - Albertsen H
FAU - Potter, John D
AU  - Potter JD
FAU - Samowitz, Wade S
AU  - Samowitz WS
LA  - eng
GR  - R01 CA059045/CA/NCI NIH HHS/United States
GR  - R01 CA048998-12A2/CA/NCI NIH HHS/United States
GR  - R01 CA59045/CA/NCI NIH HHS/United States
GR  - R01 CA048998/CA/NCI NIH HHS/United States
GR  - R01 CA61757/CA/NCI NIH HHS/United States
GR  - R01 CA48998/CA/NCI NIH HHS/United States
GR  - N01-PC-67000/PC/NCI NIH HHS/United States
GR  - R01 CA061757-11/CA/NCI NIH HHS/United States
GR  - R01 CA061757/CA/NCI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070421
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 7LP2MPO46S (S-Adenosylmethionine)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - Adult
MH  - Aged
MH  - Case-Control Studies
MH  - Colonic Neoplasms/enzymology/*genetics/*metabolism
MH  - CpG Islands/*physiology
MH  - *DNA Methylation
MH  - *Diet
MH  - Female
MH  - Humans
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/genetics
MH  - Middle Aged
MH  - Phenotype
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Single Nucleotide
MH  - S-Adenosylmethionine/genetics
PMC - PMC2442467
MID - NIHMS50859
COIS- Conflict of Interest Statement: None declared.
EDAT- 2007/04/24 09:00
MHDA- 2007/10/20 09:00
PMCR- 2008/07/01
CRDT- 2007/04/24 09:00
PHST- 2007/04/24 09:00 [pubmed]
PHST- 2007/10/20 09:00 [medline]
PHST- 2007/04/24 09:00 [entrez]
PHST- 2008/07/01 00:00 [pmc-release]
AID - bgm089 [pii]
AID - 10.1093/carcin/bgm089 [doi]
PST - ppublish
SO  - Carcinogenesis. 2007 Aug;28(8):1672-9. doi: 10.1093/carcin/bgm089. Epub 2007 Apr 
      21.