|Other Abstract||Objective: The distributions of ABCB1 rs1045642, rs1128503, rs2032582 and RPA1 rs5030740 were determined in some patients with gastric cancer in Gansu Province. To investigate whether there were associations between Single nucleotide polymorphisms (SNPs) and efficacy or adverse reactions of oxaliplatin-based chemotherapy for gastric cancer, and to predict the value of SNPs in clinical application.
Methods: In this study, 189 patients with gastric cancer receiving oxaliplatin-based chemotherapy were included. We collected the clinical and pathological characteristics of patients, such as gender, age, ethnicity, tumor location, etc. ABCB1 rs1045642 was genotyped by allele specific PCR (AS-PCR). ABCB1 rs1128503, rs2032582 and RPA1 rs5030740 were genotyped by direct sequencing. Finally, we used logistic regression to evaluate the association between SNPs and objective response rate (ORR) or disease control rate (DCR) or adverse reactions of receiving oxaliplatin-based chemotherapy in patients with gastric cancer. Logistic regression was used to analyze the association between SNPs and progression-free survival (PFS) of receiving oxaliplatin-based chemotherapy in patients with gastric cancer.
Results: (1) In ABCB1 rs1045642, the genotype frequencies of CC, CT and TT were 40.2%, 42.9% and 16.9%, respectively. The genotype frequencies of CC, CT and TT in ABCB1 rs1128503 were 10.5%, 50.3% and 39.25%, respectively. The genotype frequencies of GG, GT, GA, AA, TT and AT in ABCB1 rs2032582 were 22.7%, 32.3%, 12.7%, 2.1%, 20.1% and 10.1%, respectively. The genotype frequencies of TT, TC and CC in RPA1 rs5030740 were 62.4%, 32.3% and 5.3%, respectively. (2) In the codominant model of ABCB1 rs2032582, the DCR of GA carriers was worse than that of GG carriers (GA vs GG: OR=0.216, 95%CI=0.052-0.904, P= 0.036). (3) In ABCB1 rs2032582, the risk of grade III gastrointestinal toxicity in patients with TT was 5.543 times than that of CT+CC carriers (OR=5.543, 95%CI=1.159-26.501, P=0.032);The risk of grade III hematological toxicity in patients with TCG haplotype was 5.134 times than that of grade I-II hematological toxicity (HR=22.528, 95%CI=3.799-133.579, P=0.001;HR=19.447, 95CI%=3.393-111.464, P=0.001). (4) In RPA1 rs5030740, patients with CC had shorter PFS than TT or TT+TC carriers (HR=12.295, 95%CI=2.538-59.567, P=0.002;HR=9.449, 95%CI=2.038-43.816, P=0.004). In addition, in RPA1 rs5030740, patients with TT had longer PFS than that of TC+CC carriers (HR=2.948, 95%CI=1.169-7.434, P=0.022).
Conclusions: (1) In ABCB1 rs2032582, GA genotype was more prone to disease progression than GG genotype;(2) In the recessive model, ABCB1 rs1045642 is associated with gastrointestinal toxicity in gastric cancer treated with oxaliplatin. In TCG haplotype, the risk of grade III hematological toxicity was higher than that of grade I-II hematological toxicity;(3) The RPA1 rs5030740 is an independent prognostic factor for PFS.|