Single nucleotide polymorphisms in uracil-processing genes, intake of one-carbon nutrients and breast cancer risk.
Single nucleotide polymorphisms in uracil-processing genes, intake of one-carbon nutrients and breast cancer risk.
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DOI：
10.1038/ejcn.2011.29
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发表时间：
2011-06
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
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尿嘧啶与DNA的错误结合导致基因组不稳定。在之前的一项研究中，我们中的一些人在尿嘧啶加工基因中发现了四个常见的snp (SMUG1中的rs2029166和rs7296239， UNG中的rs34259和DUT中的rs4775748)，它们与人类DNA中尿嘧啶水平的显著改变有关。我们调查了这些snp是否与乳腺癌风险的改变有关，以及单碳营养素的摄入是否可以改变它们的影响。在纽约西部暴露和乳腺癌研究中，我们对1077例乳腺癌病例和1910例年龄和种族匹配的对照组的四个snp进行了基因分型，并检查了乳腺癌风险与叶酸、维生素B6和B12摄入量的关系。对已知的乳腺癌危险因素进行校正后，SMUG1 snp杂合的绝经后妇女患乳腺癌的风险增加（OR 1.29, 95% CI 1.07-1.56）和（1.29,1.07-1.55）。在绝经前妇女中，与SMUG1 rs2029166基因型相关的风险增加仅限于叶酸摄入量低的妇女。没有其他与维生素B6或B12摄入的相互作用。我们的研究表明，这四个选定的snp并不是乳腺癌风险的强大决定因素，但SMUG1中的两个snp可能会适度改变乳腺癌的风险。然而，SMUG1（被认为是体内最活跃的糖基酶）中两个snp的杂合子的风险增加，提出了这些snp可能对癌症风险产生微妙的“杂种优势”效应的可能性。
The misincorporation of uracil into DNA leads to genomic instability. In a prior study, some of us identified four common 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. We genotyped the four SNPs in 1,077 cases of incident breast cancer and 1,910 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. 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 SMUG1 SNPs (OR 1.29, 95% CI 1.07–1.56) and (1.29, 1.07–1.55). 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 B6 or B12 intake. 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.
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影响因子：
4.2
作者：
Giovannucci, E
通讯作者：
Giovannucci, E
影响因子：
5.9
作者：
Xu, Xinran;Chen, Jia
通讯作者：
Chen, Jia
DOI：
10.1073/pnas.94.7.3290
发表时间：
1997-04-01
影响因子：
11.1
作者：
Blount, BC;Mack, MM;Ames, BN
通讯作者：
Ames, BN
影响因子：
4.2
作者：
Jang, HR;Mason, JB;Choi, SW
通讯作者：
Choi, SW
影响因子：
5
作者：
BLOCK, G;HARTMAN, AM;GARDNER, L
通讯作者：
GARDNER, L