Ullah Shah Abid, Mahjabeen Ishrat, Kayani Mahmood Akhtar
Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
J BUON. 2015 Jul-Aug;20(4):985-93.
This study was performed to screen cyclin D1 (CCND1) and cyclin dependent kinases (CDK4) genes in order to evaluate their association with breast carcinogenesis.
The germline screening of these genes was carried out by combining polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP), followed by DNA sequence analysis. A total of 400 individuals (200 breast cancer patients and 200 healthy controls) were recruited prospectively for this study.
Sequence analyses of the coding region of CCND1 revealed 12 mutations. When analyzed, a significant association was found between CCND1 mutations and breast cancer. It was observed that a 6-fold increased breast cancer risk (odds ratio/OR=5.75, 95% confidence interval/CI=1.26-26.33) was associated with Cys7Tyr in breast cancer patients when compared with healthy controls. In addition, a 5-fold increased breast cancer risk was associated with Trp63Stop mutation (OR=5.44, 95% CI=1.82-16.23), 10861C>A (OR=4.84; 95% CI=1.60-14.58) and 7720insTT (OR=5.32, 95% CI=1.98-14.23) in breast cancer patients compared to healthy controls. Concerning CDK4 gene, 5 mutations were identified and a significant association was observed between CDK4 gene mutations and breast cancer. It was observed that a 6-fold increased risk of breast cancer (OR=5.71, 95% CI=0.29-4.65) was associated with 5693 T>A. In addition, a 5-fold increased risk of breast cancer (OR=5.05, 95% CI=2.17-11.78) was associated with 5732 G>A in breast cancer patients compared to controls.
In this study, our results showed that CCND1 and CDK4 mutations are associated with an increased risk of breast cancer, and may serve as biomarkers for early diagnosis and detection of breast cancer.
本研究旨在筛查细胞周期蛋白D1（CCND1）和细胞周期蛋白依赖性激酶（CDK4）基因，以评估它们与乳腺癌发生的关联。
通过聚合酶链反应（PCR）和单链构象多态性（SSCP）相结合的方法对这些基因进行种系筛查，随后进行DNA序列分析。本研究前瞻性招募了400名个体（200例乳腺癌患者和200例健康对照）。
CCND1编码区的序列分析发现了12个突变。分析发现，CCND1突变与乳腺癌之间存在显著关联。观察到与健康对照相比，乳腺癌患者中Cys7Tyr与乳腺癌风险增加6倍相关（优势比/OR = 5.75，95%置信区间/CI = 1.26 - 26.33）。此外，与健康对照相比，乳腺癌患者中Trp63Stop突变（OR = 5.44，95% CI = 1.82 - 16.23）、10861C>A（OR = 4.84；95% CI = 1.60 - 14.58）和7720insTT（OR = 5.32，95% CI = 1.98 - 14.23）与乳腺癌风险增加5倍相关。关于CDK4基因，鉴定出5个突变，并且观察到CDK4基因突变与乳腺癌之间存在显著关联。观察到与对照相比，5693 T>A与乳腺癌风险增加6倍相关（OR = 5.71，95% CI = 0.29 - 4.65）。此外，与对照相比，乳腺癌患者中5732 G>A与乳腺癌风险增加5倍相关（OR = 5.05，95% CI = 2.17 - 11.78）。
在本研究中，我们的结果表明CCND1和CDK4突变与乳腺癌风险增加相关，并且可能作为乳腺癌早期诊断和检测的生物标志物。
