Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Jinan, China.
Mol Genet Genomic Med. 2020 Jun;8(6):e1226. doi: 10.1002/mgg3.1226. Epub 2020 Apr 3.
Among the different types of cancer, pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is the most lethal malignancy, with poor early detection rates and prognosis. The aim of the present study was to investigate the potential genetic effects of the single-nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs3789243, rs4148737), APOB (rs693, rs1042031), CAV1 (rs12672038, rs1997623, rs3807987, rs7804372), and NAMPT (rs9034, rs2505568, rs61330082) on PDAC.
A total of 273 patients with PDAC and 263 healthy controls were genotyped using PCR and direct Sanger sequencing. Unconditional logistic regression models were used to evaluate the potential effects of the genotypes, alleles, and haplotypes on the risk of developing PDAC.
Patients with PDAC possessed a considerably lower frequency of genotypes AG, GG, and allele G at ABCB1 rs4148737 compared with controls. Based on age, sex, smoking status, drinking status, diabetes, and family history of cancer, stratified analyses showed a significant correlation between SNPs at rs4148737 and PDAC. According to specific SNPs, eight haplotypes were constructed along with ABCB1 rs4148737, rs1045642, and rs3789243. Carriers with haplotypes ACC and ATC were more susceptible to developing PDAC, whereas haplotypes GCC and GTC were associated with a reduced likelihood of developing PDAC. The distributions of the other SNPs in each group were not significantly associated with PDAC risk.
These results suggested that genetic polymorphisms of ABCB1 rs4148737 may influence an individual's risk of developing PDAC.
在各种类型的癌症中,胰腺癌,特别是胰腺导管腺癌(PDAC),是最致命的恶性肿瘤,早期检测率和预后都很差。本研究旨在探讨 ABCB1(rs1045642、rs3789243、rs4148737)、APOB(rs693、rs1042031)、CAV1(rs12672038、rs1997623、rs3807987、rs7804372)和 NAMPT(rs9034、rs2505568、rs61330082)的单核苷酸多态性(SNPs)对 PDAC 的潜在遗传影响。
使用 PCR 和直接 Sanger 测序对 273 例 PDAC 患者和 263 例健康对照进行基因分型。采用非条件逻辑回归模型评估基因型、等位基因和单倍型对 PDAC 发病风险的潜在影响。
PDAC 患者 ABCB1 rs4148737 的 AG、GG 基因型和 G 等位基因频率明显低于对照组。根据年龄、性别、吸烟状况、饮酒状况、糖尿病和癌症家族史进行分层分析显示,rs4148737 与 PDAC 之间存在显著相关性。根据特定的 SNPs,构建了包含 ABCB1 rs4148737、rs1045642 和 rs3789243 的 8 种单倍型。携带 ACC 和 ATC 单倍型的个体更容易患上 PDAC,而携带 GCC 和 GTC 单倍型的个体则不太可能患上 PDAC。每组中其他 SNPs 的分布与 PDAC 风险无显著相关性。
这些结果表明,ABCB1 rs4148737 的遗传多态性可能影响个体患 PDAC 的风险。