Department of Biochemistry, College of Science, University of Jeddah, Jeddah 80203, Saudi Arabia.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
Gene. 2020 May 5;737:144435. doi: 10.1016/j.gene.2020.144435. Epub 2020 Feb 7.
The cancer-brake gene CTLA4 has a vital function in suppressing the immune responses of activated T lymphocytes. Numerous reports explored the impact of various CTLA4 variants with the predisposition for malignancies but with unconvincing findings. Hence, this study is designed to assess the association of CTLA4 (c.49A>G, rs231775) variant with the outcome of breast carcinoma. A total of 272 participants (93 BC patients and 179 cancer-free healthy volunteers) were enrolled. Genomic DNA for all participants was genotyped for CTLA4 (c.49A>G) variant via TaqMan genotyping assay. Patients with A/G genotype conferred protection against developing BC under heterozygote comparison (OR = 0.56, 95%CI = 0.31-0.98) as well dominant model (OR = 0.55, 95%CI = 0.32-0.97). AG/GG genotypes were anchored with an increased risk of nodal infiltration (OR = 2.90, 95%CI = 1.03-8.17, P = 0.037), metastasis (OR = 4.46, 95%CI = 1.18-16.8, P = 0.019), advanced clinical stage (OR = 6.54, 95%CI = 2.06-20.75, P < 0.001), recurrence (OR = 5.2, 95%CI = 1.73-15.7, P = 0.001), and shorter survival (OR = 2.54, 95%CI = 1.08-5.99, P = 0.032). In addition, functional enrichment analysis revealed the key role of CTLA4 in cancer immunosurveillance. Our findings indicated that the CTLA4 c.49A>G variant might have prognostic as well diagnostic impact in breast cancer.
CTLA4 抑癌基因在抑制活化 T 淋巴细胞的免疫反应中具有重要作用。大量报道探讨了各种 CTLA4 变体与恶性肿瘤易感性的关系，但结果并不令人信服。因此，本研究旨在评估 CTLA4(c.49A>G，rs231775)变体与乳腺癌结局的相关性。共纳入 272 名参与者(93 名乳腺癌患者和 179 名无癌健康志愿者)。所有参与者的基因组 DNA 均通过 TaqMan 基因分型检测用于 CTLA4(c.49A>G)变体的基因分型。与杂合子比较(OR=0.56,95%CI=0.31-0.98)和显性模型(OR=0.55,95%CI=0.32-0.97)相比，A/G 基因型可预防乳腺癌的发生。AG/GG 基因型与淋巴结浸润(OR=2.90,95%CI=1.03-8.17，P=0.037)、转移(OR=4.46,95%CI=1.18-16.8，P=0.019)、晚期临床分期(OR=6.54,95%CI=2.06-20.75，P<0.001)、复发(OR=5.2,95%CI=1.73-15.7，P=0.001)和较短的生存时间(OR=2.54,95%CI=1.08-5.99，P=0.032)相关。此外，功能富集分析显示 CTLA4 在癌症免疫监测中的关键作用。我们的研究结果表明，CTLA4 c.49A>G 变体可能对乳腺癌具有预后和诊断意义。
