Soucek P, Borovanova T, Pohlreich P, Kleibl Z, Novotny J
Group for Biotransformations, Center of Occupational Medicine, National Institute of Public Health, Srobárova 48, Prague 10, Czech Republic.
Breast Cancer Res Treat. 2007 Jun;103(2):219-24. doi: 10.1007/s10549-006-9367-9. Epub 2006 Oct 13.
We aimed at determining whether any association exists between six single nucleotide polymorphisms in breast cancer associated gene (BRCA1) and the risk of breast cancer. We constructed haplotypes and analyzed their importance as well. Clinico-pathological characteristics of breast cancer patients were included in the study to evaluate the prognostic impact of BRCA1 polymorphisms and haplotypes. Polymerase chain reaction-restriction fragment length polymorphism-based genotyping assays were used to determine the frequency of polymorphisms in codons 356, 871, 1038, 1183, 1436, and 1613 of BRCA1 in a group of 306 incident breast cancer patients and 313 unaffected controls of Czech origin. Statistical analyses revealed that the BRCA1 Arg356 allele may play a protective role in breast cancer (age-adjusted OR = 0.61, CI = 0.39-0.94, p = 0.026). We also observed a significant correlation between polymorphism Gln356Arg and stage (p = 0.026) in premenopausal cases suggesting that carriers of the wild Gln356Gln allele are at significantly higher risk of advanced disease. The most common haplotypes of BRCA1 did not play a significant role in breast cancer either as risk factors or as prognostic factors. The study on rare BRCA1 haplotypes however should be repeated using larger groups. In conclusion, the BRCA1-Gln356 allele presents risk factor in the onset and progression of breast cancer in Czech population and its use as a possible screening tool should be considered.
我们旨在确定乳腺癌相关基因（BRCA1）中的六个单核苷酸多态性与乳腺癌风险之间是否存在关联。我们构建了单倍型并分析了它们的重要性。研究纳入了乳腺癌患者的临床病理特征，以评估BRCA1多态性和单倍型的预后影响。采用基于聚合酶链反应-限制性片段长度多态性的基因分型检测方法，确定了306例初发乳腺癌患者和313例捷克裔未受影响对照中BRCA1第356、871、1038、1183、1436和1613密码子多态性的频率。统计分析显示，BRCA1 Arg356等位基因可能对乳腺癌起保护作用（年龄调整后的比值比=0.61，置信区间=0.39-0.94，p=0.026）。我们还观察到绝经前病例中多态性Gln356Arg与分期之间存在显著相关性（p=0.026），这表明野生型Gln356Gln等位基因携带者患晚期疾病的风险显著更高。BRCA1最常见的单倍型作为危险因素或预后因素在乳腺癌中均未发挥显著作用。然而，关于罕见BRCA1单倍型的研究应使用更大的样本量重复进行。总之，BRCA1-Gln356等位基因是捷克人群乳腺癌发病和进展的危险因素，应考虑将其用作可能的筛查工具。
