Correlation Of Gene Polymorphisms And The Prognosis, Response To Treatment Of Patients With Triple Negative Breast Cancer

Objective The aim of this study was to investigate the association between triple negative breast cancer (TNBC) prognosis and single nucleotide polymorphisms (SNPs) of DNA repair genes, apoptosis-related genes and other closely related genes, so as to looking for the clinical helpful molecular markers to guide individualized treatment.Methods Totally172triple negative breast cancer patients treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were taken into the study. Patients were divided into two groups according to whether they had recurrence or metastasis. The clinical and pathological data were collected. Sequenom's MassARRAY system was used to detect the SNPs of candidate genes. Finally, the association between genotypes and different diseases status among patients was analyzed.Results Three genotypes were detected in rs3025039, a SNP of VEGF gene. The frequencies of CC, TT and CT genotype in the disease-free group and recurrence/metastasis group were73.2%vs.58.6%,5.2%vs.2.7%and21.6%vs.38.7%. The difference of the distribution of genotypes between tow groups was statistically significant (P=0.045). So was the distribution of the TP53rs12951053genotypes (P=0.041). The frequencies of rs12951053-AA, CC, CA genotype were36.1%vs.50.7%,13.4%vs.4.0%and50.5%vs.45.3%in the disease-free group and recurrence/metastasis group. Neither rs3025039nor rs12951053genotypes had obvious correlation with clinicopathological features (P>0.05). Logistic regression analysis showed that CT heterozygous genotype of rs3025039would increase the risk of recurrence and metastasis in TNBC patients (OR=2.228,95%CI=1.134～4.380, P=0.045). While CC genotype of TP53rs12951053was a protective factor. TNBC patients carrying the rs12951053-CC genotype wolud less likely to have recurrence and metastasis (OR=0.213,95%CI=0.056～0.809, P=0.041). There was no significant association between the risk of recurrence and metastasis and the SNPs of the rest genes (P>0.05). Multivariate Logistic regression analysis showed that besides stage, the polymorphism of TP53rs12951053was an independent prognostic factor for TNBC (OR=0.039,95%CI=0.002～0.666, P=0.025). Conclusions The rate of recurrence and metastasis is comparatively lower in TNBC patients with CC genotype of TP53rs12951053, which may be a prognostic factor for TNBC. Objective Polymorphisms of DNA repair genes may affect the repair capacity of DNA damage and cause different responses towards chemotherapy among patients. Excision repair cross-complementing group2(ERCC2) plays an important role in the nucleotide excision repair. The aim of this study is to investigate the association between ERCC2single nucleotide polymorphism (SNP) and the response to platinum-based chemotherapy among patients with triple negative breast cancer (TNBC).Methods Totally60triple negative breast cancer patients treated with platinum-based chemotherapy were studied. The clinical, pathological and treatment data of them were collected. Sequenom's MassARRAY system was used in the detection of the SNPs of ERCC2. Finally, the association between genotypes and different clinical responses among patients was analyzed.Results All of the patients received a platinum-based chemotherapy for four cycles in median and achieved an overall response rate of66.7%, showing a comparative good response towards platinum-based chemotherapy among TNBC. Fifty-three of the sixty patients had got the results of rs1799793polymorphisms after MassARRAY detection. The proportion of GG genotype and GA genotype was81.1%and18.9%respectively. The response rate of the rs1799793GG genotype group was69.8%, while the GA genotype group only had a response rate of30.0%. It turned out that the GG genotype was associated with better response towards platinum-based chemotherapy (P=0.030).Conclusions Polymorphism of rs1799793may be associated with the clinical sensitivity of platinum-based chemotherapy and could be a potential predictive biomarker for TNBC patients treated with platinum compounds.