Role of CYP1A2 polymorphisms in breast cancer risk in women
Role of CYP1A2 polymorphisms in breast cancer risk in women
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DOI：
10.3892/mmr.2012.1164
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发表时间：
2013-01-01
影响因子：
3.4
通讯作者：
Pavanello, Sofia
中科院分区：
文献类型：
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作者：
Ayari, Imene;Fedeli, Ugo;Pavanello, Sofia
细胞色素P4501 A2（CYP 1A 2）是乳腺癌（BC）发病的关键酶。它参与乳腺癌原活化[芳香族（AAs）和杂环胺（HAs），多环芳烃（PAH）]，产生有益的雌激素[2-羟基雌酮（2-OHE 1）]，并将花生四烯酸（AAc）转化为具有抗炎特性的环氧二十碳三烯酸（EHF）。在一项基于医院的病例对照研究中，研究了功能性CYP 1A 2变体[-3860 G/A（rs 2069514），-2467 T/delT（rs3569413），-163 C/A（rs762551）]及其与BC风险环境因素的相互作用。研究人群包括125例BC病例和43例非癌症对照。使用Taqman测定在RT-PCR中进行基因分型。基因与环境的相互作用采用病例研究设计进行评价。我们发现，-3860A变异，独立于环境因素，以及通过与油炸食品（p=0.025）和室内暴露于污染物（p=0.050）的相互作用，降低了BC的风险（p=0.025），而其与咖啡（p=0.045）的相互作用增加了BC的风险。这是第一项研究表明，-3860A变体通过降低CYP 1A 2活性，通过与环境因素相互作用来改变BC风险，从而支持CYP 1A 2活性降低以不同方式促进BC风险的假设，例如，它可能通过减少促致癌物如AA，HA和PAH的活化而具有保护作用，但会通过减少2-OHE 1和Ehrs的有益形成而增加风险。
Cytochrome P4501A2 (CYP1A2) is a key enzyme in the etiology of breast cancer (BC). It is involved in breast carcinogen activation [aromatic (AAs) and heterocyclic amines (HAs), polycyclic aromatic hydrocarbons (PAHs)], in the production of beneficial oestrogen [2-hydroxyestrone (2-OHE1)] and in converting arachidonic acid (AAc) to epoxyeicosatrienoic acids (EETs), which have anti-inflammatory properties. Within a hospital-based case-control study, the effect of functional CYP1A2 variants [-3860G/A (rs2069514), -2467T/delT (rs3569413), -163C/A (rs762551)] and their interactions with environmental factors in BC risk was investigated. The study population included 125 BC cases and 43 non-cancer controls. Genotyping was performed in RT-PCR using Taqman assays. The gene-environment interaction was appraised using a case-only study design. We found that the -3860A variant, independently from environmental factors, as well as by interacting with fried foods (p=0.025) and indoor exposure to pollutants (p=0.050), reduced the risk of BC (p=0.025), whereas its interaction with coffee (p=0.045) increased the BC risk. This is the first study indicating that the -3860A variant, by decreasing CYP1A2 activity, modifies BC risk by interacting with environmental factors, thereby supporting the hypothesis that reduced CYP1A2 activity contributes to BC risk in different ways, for example, it may be protective by reducing the activation of pro-carcinogens such as AAs, HAs and PAHs, but would increase risk by reducing the beneficial formation of 2-OHE1 and EETs.