Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G2 chromosomal radiosensitivity
Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G2 chromosomal radiosensitivity
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DOI：
10.1002/em.20274
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发表时间：
2007-01-01
影响因子：
2.8
通讯作者：
Boice, John D., Jr.
中科院分区：
文献类型：
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作者：
Wilding, Craig S.;Curwen, Gillian B.;Boice, John D., Jr.
在83名受试者中检测了来自4种DNA修复途径的9个基因的16个候选多态性（13个SNP和3个微卫星），包括23名儿童癌症幸存者，他们的23名伴侣和37名后代，所有这些人都曾进行过G（2）染色体放射敏感性研究。碱基切除修复（BER）途径的APEX基因中Asp 148 Glu SNP位点的基因型与幸存者中的儿童癌症相关（P = 0.001，即使在多重检验调整后也具有显著性），这是由于与其伴侣相比，幸存者中APEX Asp 148等位基因的频率增加。合并样本中G（2）放射敏感性的方差分析（ANOVA）以及家系数据的基于家系的关联检验（FBAT）显示，在两个位点G（2）放射敏感性和多态性之间存在零星的关联（通过ANOVA分析同源重组途径的XRCC 3基因中的Thr 241-Met SNP位点，和BER途径的hOGG 1基因中的Ser 326 Cys位点（通过FBAT分析），但在多重检验调整后，这两个位点均不显著。这项初步研究提供了一个有趣的迹象，DNA修复基因多态性可能是癌症易感性和放射敏感性变化的基础。
Sixteen candidate polymorphisms (13 SNPs and 3 microsatellites) in nine genes from four DNA repair pathways were examined in 83 subjects, comprising 23 survivors of childhood cancer, their 23 partners, and 37 offspring, all of whom had previously been studied for G(2) chromosomal radiosensitivity. Genotype at the Asp148Glu SNP site in the APEX gene of the base excision repair (BER) pathway was associated with childhood cancer in survivors (P = 0.001, significant even after multiple test adjustment), due to the enhanced frequency of the APEX Asp 148 allele among survivors in comparison to that of their partners. Analysis of variance (ANOVA) of G(2) radiosensitivity in the pooled sample, as well as family-based association test (FBAT) of the family-wise data, showed sporadic suggestions of associations between G(2) radiosensitivity and polymorphisms at two sites (the Thr241-Met SNP site in the XRCC3 gene of the homologous recombinational pathway by ANOVA, and the Ser326Cys site in the hOGG1 gene of the BER pathway by FBAT analysis), but neither of these remained significant after multiple-test adjustment. This pilot study provides an intriguing indication that DNA repair gene polymorphisms may underlie cancer susceptibility and variation in radiosensitivity.