Clinical Epidemiology Unit, National Cancer Research Institute, Largo R Benzi 10, 16132 Genoa, Italy.
Br J Cancer. 2012 Feb 14;106(4):780-90. doi: 10.1038/bjc.2011.567. Epub 2011 Dec 20.
The cytokinesis-block micronucleus test (MNT), as a marker of chromosomal mutagen sensitivity, was applied in a number of studies enrolling breast cancer (BC) patients and subjects with known or putative genetic predisposition to BC. The large majority of them involve the evaluation of induced micronuclei (MN) frequency in peripheral lymphocytes, after the in vitro challenge with ionising radiations.
The aim of the present systematic review and meta-analysis is to investigate the role of MN assay in the identification of individuals at increased risk of BC and its potential use as prescreening test in women with a family history (FH) of BC.
Twelve studies were included in the meta-analysis, covering a time interval 1998-2007, and including 752 cases and 593 controls. Among the cases, 629 are cancer patients and 123 are cancer-free subjects, including 32 first-degree relatives of the susceptible subjects and 91 BRCA1/2 mutation carriers. Our meta-analysis reveals a significant increase of baseline MN frequency related to cancer status, but the association with FH of BC and specifically with BRCA mutations is not clear. A larger difference in MN frequency between cases and controls was observed after in vitro challenge, but response to radiation exposure doesn't appear to better discriminate cancer-susceptible subjects.
Our study suggests the presence of some bias affecting many of these studies, reinforcing the suggestion that a more rigorous study design is needed in this area.
细胞分裂阻断微核试验(MNT)作为染色体诱变敏感性的标志物,已应用于许多研究中,这些研究涉及乳腺癌(BC)患者和已知或假定具有 BC 遗传易感性的受试者。其中绝大多数研究涉及体外用电离辐射对其外周血淋巴细胞进行微核诱导频率的评估。
本系统综述和荟萃分析旨在探讨 MN 检测在识别 BC 高危人群中的作用及其在有 BC 家族史的女性中作为初筛试验的潜在用途。
荟萃分析共纳入 12 项研究,时间跨度为 1998-2007 年,共纳入 752 例病例和 593 例对照。其中 629 例为癌症患者,123 例为非癌症患者,包括 32 例易感性患者的一级亲属和 91 例 BRCA1/2 突变携带者。我们的荟萃分析显示,基线 MN 频率与癌症状态相关的显著增加,但与 BC 的家族史和特别是 BRCA 突变的关联尚不清楚。体外挑战后观察到病例与对照组之间的 MN 频率差异更大,但对辐射暴露的反应似乎不能更好地区分易感性患者。
我们的研究表明,这些研究中存在一些影响因素的偏倚,这进一步提示在该领域需要更严格的研究设计。