A candidate gene study of one-carbon metabolism pathway genes and colorectal cancer risk.
The risk of colorectal cancer (CRC) may be influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by impaired dietary folate intake as well as by polymorphic variants in one-carbon metabolism genes. A case-control study using seventy-one CRC patients and eighty unrelated healthy controls was carried out to assess the genetic association of fifteen SNP and one insertion in nine genes belonging to the folate pathway. Polymorphism selection was based on literature data, and included those which have a known or suspected functional impact on cancer and missense polymorphisms that are most likely to alter protein function. Genotyping was performed by real-time PCR and PCR followed by restriction analysis. The likelihood ratio statistic indicated that most of the polymorphisms were not associated with the risk of CRC. However, an increased risk of CRC was observed for two variant alleles of SNP mapping on the transcobalamin 2 gene (TCN2): C776G (rs1801198) and c.1026-394T>G (rs7286680). Considering the crucial biological function played by one-carbon metabolism genes, further investigations with larger cohorts of CRC patients are needed in order to confirm our preliminary results. These preliminary results indicate that TCN2 polymorphisms can be a susceptibility factor for CRC.
Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Bologna, Italy.
Marcella
M
Martinelli
Luca
L
Scapoli
Gabriella
G
Mattei
Giampaolo
G
Ugolini
Isacco
I
Montroni
Davide
D
Zattoni
Giancarlo
G
Rosati
Rossella
R
Solmi
D000368:Aged; D002244:Carbon / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000378:metabolism; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000378:metabolism; D016254:Mutagenesis, Insertional; D009711:Nucleotides / Q000096:biosynthesis; D019875:One-Carbon Group Transferases; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014155:Transcobalamins / Q000235:genetics*; D014805:Vitamin B 12 / Q000378:metabolism
D009711:Nucleotides; D014155:Transcobalamins; D002244:Carbon; D005492:Folic Acid; D008715:Methionine; D019875:One-Carbon Group Transferases; D014805:Vitamin B 12