Study of relationship between polymorphisms of DPYD, ABCB1, GSTP1, ERCC1 genes and clinical features, adverse reactions and prognosis of advanced colonic cancer

Objective Detecting the polymorphism of drug genes in patients with advanced colorectal cancer, and analyze its relationship with clinical features, adverse reactions and prognosis of oxaliplatin and fluorouracil based chemotherapy. Methods Peripheral blood of 108 patients with advanced colorectal cancer who were hospitalized in our department from March 2016 to May 2018 was collected. Single-nucleotide polymorphisms (SNP) were performed on the DPYD, ABCB1, GSTP1, and ERCC1 genes by Life platform assay to compare the differences between different genotypes and patients′ KRAS status, tumor location (left and right), adverse reactions, and median disease progression time (PFS). Results 108 patients with advanced colorectal cancer were included, four sites of DPYD (rs3918290, rs55886062, rs67376798, rs2297595) were wild type, fifty-two cases (48.1%) were ERCC1 (rs11615) GG gene, 50 (46.3%) were AG gene, 6 (5.6%) were AA wild type gene, 36 cases (33.3%) of GSTP1 (rs1695) were AG heterozygous mutation, sixty-six cases (66.1%) of AA wild type, six cases of GG pure and mutant type (5.6%). Fifty-eight cases (53.7%) of ABCB1 (rs1045642) were AG heterozygous gene, fourty-two cases (38.9%) were GG type gene, eight cases (7.4%) of AA wild type. Tumors located in the left and right colon and ERCC1 gene distribution was related (χ2=4.802, P=0.028) and was not related to the frequency of GSTP1 and ABCB1 gene distribution. The ABCB1 AG type rate was 42.9% in KRAS mutation patients and 72.7% in wild type patients, which were statistically different (χ2=3.939, P=0.047). GSTP1 AG type and GG type are more likely to produce 2~3 grade systemic adverse reactions than AA type (77.8% vs. 45.5%, χ2=5.193; P=0.023). The grade 3~4 adverse reaction rate of patients of ABCB1 GG type and AA type was 32.9%, compared with the adverse reaction rate of 62.1% for patients with type AG (χ2=4.8.62, P=0.027). The median disease progression time (PFS) was not associated with ABCB1 and GSTP1 gene polymorphisms, and was associated with different ERCC1 genotypes. The ERRC1 heterozygous mutation (AG type) patients has a shorter PFS than GG and AA type (5.6 m vs. 8.0 m, P=0.029). Conclusions The detection of gene polymorphism has clinical value, suggesting adverse reactions and prognosis for advanced colorectal cancer chemotherapy, and providing effective guidance for patients to adjust chemotherapy. Key words: Colorectal neoplasms; SNP; DPYD; ABCB1; GSTP1; ERCC1; Adverse reactions; Prognosis