Impact of genetic variants of ABCB1, APOB, CAV1, and NAMPT on susceptibility to pancreatic ductal adenocarcinoma in Chinese patients

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: These results suggested that genetic polymorphisms of ABCB1 rs4148737 may influence an individual's risk of developing PDAC.