This study comprehensively investigated associations between genetic variants in FOCM and CRC risk and whether the FOCM nutrient status modified these associations.
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From Wiley Online Library
Genetic variants in folate-mediated one-carbon metabolism (FOCM) genes and their interactions with nutritional factors were related to an increased risk of colorectal cancer (CRC) among postmenopausal women, according to a study published online in the journal Cancer.
In this study by the Women’s Health Initiative, 288 candidate and tagging single-nucleotide polymorphisms (SNPs) in 30 FOCM genes were genotyped for 821 CRC case-control patched pairs.
At baseline, FOCM biomarkers, such as red blood cell (RBC) folate, plasma folate, pyridoxal-5’-phospate (PLP), vitamin B12, and homocysteine were measured, along with self-reported alcohol consumption.
Results showed statistically significant associations between three functionally defined candidate SNPs (methylenetetrahydrofolate dehydrogenase 1 (MTHFD1; K134R), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR; P450R), and PR domain containing 2 with ZNF domain (PRDM2; S450N)) and one literature candidate SNP (thymidylate synthase (TYMS; g.676789A>T; nominal P <0 .05).
Tagging SNPs in cystathionine-β-synthase (CBS), dihydrofolate reductase (DHFR), DNA (cytosine-5-)-methyltransferase 3β (DNMT3B), methionine adenosyltransferase I α (MAT1A),MTHFD1, and MTRR (nominal P < .05; adjusted P, not significant) also showed suggestive associations.
Nutrient biomarkers and candidate polymorphisms were noted as effect modifiers of genetic influences, including plasma/RBC folate and folate hydrolase 1 (FOLH1), paraoxonase 1 (PON1), transcobalamin II (TCN2), DNMT1, and DNMT3B; plasma PLP and TYMS TS3; plasma B12 and betaine-homocysteine S-methyltransferase 2 (BHMT2); and 4) homocysteine and methylenetetrahydrofolate reductase (MTHFR) and alanyl–transfer RNA synthetase (AARS).
This study comprehensively investigated associations between genetic variants in FOCM and CRC risk and whether the FOCM nutrient status modified these associations.
READ FULL ARTICLE
From Wiley Online Library
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