Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia.
Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia.
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DOI：
10.1007/s10552-011-9795-7
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发表时间：
2011-09
影响因子：
2.3
通讯作者：
Buffler, Patricia A.
中科院分区：
文献类型：
--
作者：
Metayer, Catherine;Scelo, Ghislaine;Chokkalingam, Anand P.;Barcellos, Lisa F.;Aldrich, Melinda C.;Chang, Jeffrey S.;Guha, Neela;Urayama, Kevin Y.;Hansen, Helen M.;Block, Gladys;Kiley, Vincent;Wiencke, John K.;Wiemels, Joseph L.;Buffler, Patricia A.
叶酸参与一碳代谢，在DNA的合成，修复和甲基化中起着重要作用。我们研究了叶酸途径中儿童的生殖系遗传变异是否与儿童急性淋巴细胞白血病（ALL）相关，以及围产期母亲叶酸和酒精摄入是否会改变风险。对377例ALL患者和448例对照者进行了76个单核苷酸多态性（SNPs）基因分型，其中66个单倍型标记SNPs分布于10个基因（CBS、DHFR、FOLH 1、MTHFD 1、MTHFR、MTR、MTRR、SHMT 1、SLC 19 A1和TYMS）。基因型和ALL风险之间的对数加性关联根据年龄、性别、西班牙裔种族（适当时）和母亲种族进行调整。单倍型和单倍型SNPs分析显示，位于CBS、MTRR、TYMS/ENOFS（或邻近）的SNPs与儿童ALL之间存在统计学显著相关性。CBS的许多区域与西班牙裔和非西班牙裔儿童ALL相关（P <0.01）。母体叶酸摄入水平改变了CBS、MTRR和TYMS中SNP的相关性。我们的数据表明叶酸途径的遗传变异性和儿童ALL风险的重要性。
Folate is involved in the one-carbon metabolism that plays an essential role in the synthesis, repair and methylation of DNA. We examined whether child’s germline genetic variation in the folate pathway is associated with childhood acute lymphoblastic leukemia (ALL), and whether periconception maternal folate and alcohol intake modify the risk. Seventy-six single nucleotide polymorphisms (SNPs), including 66 haplotype-tagging SNPs in 10 genes (CBS, DHFR, FOLH1, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS) were genotyped in 377 ALL cases and 448 controls. Log-additive associations between genotypes and ALL risk were adjusted for age, sex, Hispanic ethnicity (when appropriate), and maternal race. Single and haplotype SNPs analyses showed statistically significant associations between SNPs located in (or adjacent to) CBS, MTRR, TYMS/ENOFS and childhood ALL. Many regions of CBS were associated with childhood ALL in Hispanics and non-Hispanics (P <0.01). Levels of maternal folate intake modified associations with SNPs in CBS, MTRR, and TYMS. Our data suggest the importance of genetic variability in the folate pathway and childhood ALL risk.
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