Gestational mutations and carcinogenesis
Gestational mutations and carcinogenesis
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DOI：
10.1016/j.mbs.2005.06.003
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发表时间：
2005-10-01
影响因子：
4.3
通讯作者：
Moolgavkar, SH
中科院分区：
文献类型：
--
作者：
Meza, R;Luebeck, EG;Moolgavkar, SH
我们提出了一个数学公式来评估妊娠突变对癌症风险的影响。癌症的危险或发病函数用出生时正常细胞和突变细胞的数量的概率母函数(PGF)来表示。利用过滤泊松过程理论，我们得到了几种妊娠突变累积模型的PGF。特别是，当怀孕期间可能发生一个或两个连续突变时，我们推导出风险函数的表达式。我们还计算了当背景妊娠突变率因暴露于诱变剂(如产前辐射)而增加时的风险。为了说明我们的模型的使用，我们将它们应用于SEER数据库中的结直肠癌。我们发现，可归因于发育突变的癌症风险比例取决于年龄，当妊娠突变率很高时，这一比例可能会非常显著。对SEER数据的分析还表明，妊娠突变可能导致结直肠癌风险的个体间差异。(C)2005 Elsevier Inc.保留所有权利。
We present a mathematical formulation to evaluate the effects of gestational mutations on cancer risk. The hazard or incidence function of cancer is expressed in terms of the Probability Generating Function (PGF) of the number of normal and mutated cells at birth. Using Filtered Poisson Process Theory, we obtain the PGF for several models for the accumulation of gestational mutations. In particular, we develop expressions for the hazard function when one or two successive mutations could occur during gestation. We also calculate the hazard when the background gestational mutation rates are increased due to exposure to mutagens, such as prenatal radiation. To illustrate the use of our models, we apply them to colorectal cancer in the SEER database. We find that the proportion of cancer risk attributable to developmental mutations depends on age and that it could be quite significant when gestational mutation rates are high. The analysis of the SEER data also shows that gestational mutations could contribute to inter-individual variations in colorectal cancer risk. (c) 2005 Elsevier Inc. All rights reserved.