The correlation between genetic variation and expression of DLL1 gene and bone marrow suppression after neoadjuvant chemotherapy for breast cancer / 中华内分泌外科杂志

ABSTRACT

Objective:To investigate the effects of two SNP sites of delta-like ligand protein-1 (DLL1) gene rs2738822 (C>T) and rs9459988 (T>G) and gene expression on bone marrow suppression after neoadjuvant chemotherapy for breast cancer.Methods:Breast cancer patients who received neoadjuvant chemotherapy were selected as study subjects, including 90 patients with severe bone marrow suppression and 72 patients with mild bone marrow suppression. Patient’s demographic characteristics and laboratory test indicators were collected. Two SNP sites of DLL1, rs2738822 and rs9459988, were genotyped by capillary electrophoresis and section analysis (SNaPshot) . The relative mRNA expression of DLL1 gene was detected by quantitative reverse polymerase chain reaction (QRT-PCR) method.Results:For The rs2738822 of DLL1 gene, the genotype distribution difference between severe and mild bone marrow suppression groups was statistically significant ( χ2=8.622, P=0.013) . Compared with CC genotype, CT and TT genotype carriers had a higher risk of severe bone marrow suppression, with an OR value of 2.746 (1.335-6.882) and 3.054 (1.282-8.143) , respectively. The dominant model results showed that TT OR CT carriers had a significantly higher risk of severe bone marrow suppression than THOSE with CC genotype [ OR=2.976 (1.231-4.963) ]. For rs9459988, there was no significant difference in genotype distribution between severe bone marrow suppression group and mild bone marrow suppression group ( χ2=2.149, P=0.342) . Results of the dominant model showed that TG or GG carriers had a significantly higher risk of severe bone marrow suppression than TT carriers, with an OR value of 2.046 (1.053-5.611) . The relative mRNA expression level of DLL1 gene was 1.15±0.23 in patients with severe bone marrow suppression, which was significantly lower than that in patients with mild bone marrow suppression (2.64±0.51) ( t=6.381, P<0.001) . For rs2738822, with the increase of T allele, the relative mRNA expression level of DLL1 gene decreased gradually ( P<0.05) . For rs9459988, the relative mRNA expression level of DLL1 gene in patients with mutant allele G was also significantly lower than that in wild-type CC carriers ( P<0.05) . Conclusion:Mutations of DLL1 genes rs2738822 and rs9459988 are related to the occurrence of severe bone marrow suppression after neoadjuvant chemotherapy for breast cancer, and can be used as a genetic marker to predict the degree of bone marrow suppression after neoadjuvant chemotherapy for breast cancer patients.