ATM polymorphisms as risk factors for prostate cancer development.
ATM polymorphisms as risk factors for prostate cancer development.
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DOI：
10.1038/sj.bjc.6602007
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发表时间：
2004-08-16
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
已知 BRCA2 种系突变携带者患前列腺癌的风险较高，BRCA1 和 CHEK2 突变携带者也可能增加。这些基因是 ATM 依赖性 DNA 损伤信号通路的组成部分。为了评估 ATM 本身变异可能与前列腺癌风险相关的假设，我们对 637 名前列腺癌患者和 445 名无癌症家族史的对照者的 DNA 中的 5 个 ATM 变异进行了基因分型。在病例和对照之间，5557G>A (D1853N)、5558A>T (D1853V)、ivs38-8t>c 和 ivs38-15g>c 等位基因变异频率没有显着差异。然而，3161G (P1054R) 变异等位基因与患前列腺癌的风险增加显着相关（任何 G 与 CC OR 2.13，95% CI 1.17–3.87，P=0.016）。携带纯合子状态的 3161G 和 2572C (858L) 变体的类淋巴母细胞系在暴露于电离辐射后显示出与携带野生型 ATM 基因的细胞系显着不同的细胞周期进展概况。这些结果提供证据表明，ATM 基因中常见变异的存在可能会导致细胞表型改变，并且 ATM 3161C>G 变异可能与前列腺癌风险相关。
The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be associated with prostate cancer risk, we genotyped five ATM variants in DNA from 637 prostate cancer patients and 445 controls with no family history of cancer. No significant differences in the frequency of the variant alleles at 5557G>A (D1853N), 5558A>T (D1853V), ivs38-8t>c and ivs38-15g>c were found between the cases and controls. The 3161G (P1054R) variant allele was, however, significantly associated with an increased risk of developing prostate cancer (any G vs CC OR 2.13, 95% CI 1.17–3.87, P=0.016). A lymphoblastoid cell line carrying both the 3161G and the 2572C (858L) variant in the homozygote state shows a cell cycle progression profile after exposure to ionising radiation that is significantly different to that seen in cell lines carrying a wild-type ATM gene. These results provide evidence that the presence of common variants in the ATM gene, may confer an altered cellular phenotype, and that the ATM 3161C>G variant might be associated with prostate cancer risk.
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影响因子：
168.9
作者：
Grönberg, H
通讯作者：
Grönberg, H
DOI：
10.1073/pnas.190030497
发表时间：
2000-09-12
影响因子：
11.1
作者：
Matsuoka, S;Rotman, G;Elledge, SJ
通讯作者：
Elledge, SJ
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Sandoval, N;Platzer, M;Schindler, D
通讯作者：
Schindler, D
影响因子：
3.9
作者：
Simard, J;Dumont, M;Tavtigian, SV
通讯作者：
Tavtigian, SV