Single nucleotide polymorphisms in uracil-processing genes, intake of one-carbon nutrients and breast cancer risk.

OBJECTIVE

The misincorporation of uracil into DNA leads to genomic instability. In a previous study, some of us identified four common single nucleotide polymorphisms (SNPs) in uracil-processing genes (rs2029166 and rs7296239 in SMUG1, rs34259 in UNG and rs4775748 in DUT) that were associated with significantly altered levels of uracil in human DNA. We investigated whether any of these SNPs are associated with an altered risk of developing breast cancer and if one-carbon nutrients intake can modify their effects.

METHODS

We genotyped the four SNPs in 1077 cases of incident breast cancer and 1910 age and race-matched controls in the Western New York Exposures and Breast Cancer (WEB) Study and examined associations with breast cancer risk and interactions with intake of folate, vitamins B6 and B12.

RESULTS

After adjustment for known risk factors for breast cancer, there was increased risk of breast cancer among postmenopausal women who were heterozygous for either of the two SMUG1 SNPs (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.07-1.56) and OR 1.29, 95% CI 1.07-1.55, respectively). Among premenopausal women, increased risk associated with the SMUG1 rs2029166 genotype was limited to those with low folate intake. There were no other interactions with vitamins B(6) or B(12) intake.

CONCLUSIONS

Our study suggests that the four selected SNPs are not robust determinants of breast cancer risk, but that the two SNPs in SMUG1 might modestly alter the risk of breast cancer. However, the increase in risk among heterozygotes in the two SNPs in SMUG1, which is thought to be the most active glycosylase in vivo, raises the possibility that subtle 'heterosis' effects on cancer risk might be produced by these SNPs.