Certain Genes Associated with Colorectal Cancer Risk in Postmenopausal Women

the Cancer Therapy Advisor take:

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).