Department of Biotechnology, Visva-Bharati, Santiniketan, Birbhum, West Bengal, India.
Department of Radiation Oncology, Eden Medical Centre, Dimapur, Nagaland, India.
Asian Pac J Cancer Prev. 2021 Apr 1;22(4):1171-1181. doi: 10.31557/APJCP.2021.22.4.1171.
The association of BAX -248 G>A and BCL2 -938 C>A with different cancers created conflicts. We studied the correlation and the effect of these polymorphisms in patients with Nasopharyngeal Carcinoma (NPC). Methods: PCR-RFLP and Sanger sequencing were used to detect polymorphisms. Statistical analysis including forest plot and Kaplan-Meier Log-rank test was conducted to investigate the association and effect of these SNPs on the NPC patients' survival. The computational study was performed to investigate the possible regulatory role between these polymorphisms and the poor survival of NPC patients. Meta-analysis was executed to check the tissue-specific association of these polymorphisms in the context of global cancer prognosis.
We observed an increased and significant association of BAX -248 G>A [GA:OR=5.29, 95%CI=1.67,16.67, P=0.004; GA+AA:OR=5.71, 95%CI=1.82,17.90, P =0.002; A:OR=5.33, 95%CI=1.76,16.13, P=0.003], and BCL2 -938 C>A [CA:OR=2.26, 95%CI=1.03,4.96, P=0.04; AA:OR=3.56, 95%CI=0.97,13.05, P=0.05; CA+AA:OR=3.10, 95%CI=1.51,6.35, P=0.002; A:OR=2.90, 95% CI=1.59,5.29, P=0.0005] with the risk of NPC. Also, these SNPs were strongly correlated with poor survival in NPC patients (lower estimated survival mean, lower estimated proportion surviving at 5 years with p <0.05). The computational study showed that these SNPs altered the binding affinity of transcription factors HIF1, SP1, PAX3, PAX9 and CREB towards promoter (Lower p indicates strong affinity). The meta-analysis revealed the tissue-specific association of these polymorphisms. BAX -248 G>A showed a significant correlation with carcinomas [A vs G:OR=1.60, 95%CI=1.09,2.34, P=0.01; AA vs GG:OR=2.61, 95%CI=1.68,4.06, p <0.001; AA+GA vs GG:OR=1.53,95%CI=1.04,2.25, P=0.02); AA vs GG+GA:OR=2.53, 95%CI=1.65,3.87, p <0.001], and BCL2 -938 C>A with other malignancies [A vs C:OR=1.45, 95%CI=1.26,1.66, p <0.001; AA vs CC:OR=2.07, 95%CI: 1.15,3.72, P=0.01; AA+CA vs CC:OR=1.42, 95%CI=1.18,1.72, p <0.001; AA vs CC+CA:OR=1.89, 95%CI=1.02,3.50, P=0.04].
BAX -248 G>A and BCL2 -938 C>A was associated with poor survival in NPC patients. It may increase cancer susceptibility through transcriptional regulation. Moreover, these SNPs' effects could be tissue-specific.
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BAX-248 G>A 和 BCL2-938 C>A 与不同癌症的关联存在冲突。我们研究了这些多态性在鼻咽癌（NPC）患者中的相关性及其对 NPC 患者生存的影响。
采用 PCR-RFLP 和 Sanger 测序法检测多态性。通过森林图和 Kaplan-Meier Log-rank 检验进行统计分析，以研究这些 SNP 与 NPC 患者生存的相关性和影响。采用计算研究来研究这些多态性与 NPC 患者不良预后之间的可能的调控作用。执行荟萃分析以检查这些多态性在全球癌症预后中的组织特异性关联。
我们观察到 BAX-248 G>A [GA：OR=5.29，95%CI=1.67，16.67，P=0.004；GA+AA：OR=5.71，95%CI=1.82，17.90，P=0.002；A：OR=5.33，95%CI=1.76，16.13，P=0.003]和 BCL2-938 C>A [CA：OR=2.26，95%CI=1.03，4.96，P=0.04；AA：OR=3.56，95%CI=0.97，13.05，P=0.05；CA+AA：OR=3.10，95%CI=1.51，6.35，P=0.002；A：OR=2.90，95%CI=1.59，5.29，P=0.0005]与 NPC 的风险增加相关。此外，这些 SNP 与 NPC 患者的不良预后密切相关（较低的估计生存率，较低的 5 年估计生存率，p<0.05）。计算研究表明，这些 SNP 改变了转录因子 HIF1、SP1、PAX3、PAX9 和 CREB 对启动子的结合亲和力（较低的 p 表示较强的亲和力）。荟萃分析显示这些多态性具有组织特异性。BAX-248 G>A 与癌有显著相关性[A 与 G：OR=1.60，95%CI=1.09，2.34，P=0.01；AA 与 GG：OR=2.61，95%CI=1.68，4.06，p<0.001；AA+GA 与 GG：OR=1.53，95%CI=1.04，2.25，P=0.02]；AA 与 GG+GA：OR=2.53，95%CI=1.65，3.87，p<0.001），BCL2-938 C>A 与其他恶性肿瘤有相关性[A 与 C：OR=1.45，95%CI=1.26，1.66，p<0.001；AA 与 CC：OR=2.07，95%CI：1.15，3.72，P=0.01；AA+CA 与 CC：OR=1.42，95%CI=1.18，1.72，p<0.001；AA 与 CC+CA：OR=1.89，95%CI=1.02，3.50，P=0.04]。
BAX-248 G>A 和 BCL2-938 C>A 与 NPC 患者的不良预后相关。它可能通过转录调控增加癌症易感性。此外，这些 SNP 的影响可能具有组织特异性。
