Polymorphisms in uracil-processing genes, but not one-carbon nutrients, are associated with altered DNA uracil concentrations in an urban Puerto Rican population.
BACKGROUND
Five genes--UNG, SMUG1, MBD4, TDG, and DUT--are involved in the repair or prevention of uracil misincorporation into DNA, an anomaly that can cause mutagenic events that lead to cancer. Little is known about the determinants of uracil misincorporation, including the effects of single nucleotide polymorphisms (SNPs) in the abovementioned genes. Because of their metabolic function, folate and other one-carbon micronutrients may be important factors in the control of uracil misincorporation.


OBJECTIVE
We sought to identify polymorphisms in uracil-processing genes that are determinants of DNA uracil concentration and to establish whether one-carbon nutrient status can further modify their effects.


METHODS
We examined the relations between 23 selected variants in the 5 uracil-processing genes, uracil concentrations in whole-blood DNA, and one-carbon nutrient (folate, vitamins B-6 and B-12, and riboflavin) status in 431 participants of the Boston Puerto Rican Health Study.


RESULTS
Four SNPs in DUT, UNG, and SMUG1 showed a significant association with DNA uracil concentration. The SNPs in SMUG1 (rs2029166 and rs7296239) and UNG (rs34259) were associated with increased uracil concentrations in the variant genotypes (P = 0.011, 0.022, and 0.045, respectively), whereas the DUT SNP (rs4775748) was associated with a decrease (P = 0.023). In this population, one-carbon nutrient status was not associated with DNA uracil concentration, and it did not modify the effect of these 4 identified SNPs.


CONCLUSIONS
Because elevated uracil misincorporation may induce mutagenic lesions, possibly leading to cancer, we propose that the 4 characterized SNPs in DUT, UNG, and SMUG1 may influence cancer risk and therefore deserve further investigation.
Chanson
Aurelie
A
Jean Mayer US Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Parnell
Laurence D
LD
Ciappio
Eric D
ED
Liu
Zhenhua
Z
Crott
Jimmy W
JW
Tucker
Katherine L
KL
Mason
Joel B
JB
D000368:Aged; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005787:Gene Frequency; D005796:Genes; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D014498:Uracil / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D014803:Vitamin B Complex / Q000097:blood*
D014803:Vitamin B Complex; D014498:Uracil; D004247:DNA