Abstract
Compared with other subgroups of breast cancer, triple negative breast cancer (TNBC) is considered to be the one with the greatest invasiveness and metastatic mobility, and the highest recurrence rate. Considering the lack of predictive markers for TNBC, we aimed to examine the contribution of excision repair cross complementing-group 1 (ERCC1) genotypes to TNBC. The rs11615 and rs3212986 of ERCC1 were investigated and evaluated for their associations with susceptibility to breast cancer, especially TNBC, in Taiwan. In this study, 1,232 breast cancer patients (104 were TNBC) and 1,232 healthy controls were recruited and their genotypes at ERCC1 rs11615 and rs3212986 were revealed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Our results indicated that genotypes of ERCC1 rs11615 (Ptrend = 2.2*10E-9), but not rs3212986 (Ptrend = 0.6181), were associated with breast cancer risk. In the allelic frequency distribution analysis, breast cancer patients carried the T allele of ERCC1 rs11615 a higher rate than the control subjects, further supporting the idea that ERCC1 rs11615 TT genotype is positively associated with breast cancer susceptibility. More importantly, the frequency of the ERCC1 rs11615 TT genotype was even higher among TNBC patients than among other subtypes of breast cancer patients (P = 0.0001, odds ratio = 1.73, 95% confidence interval = 1.15–2.63). The genotypes of ERCC1 rs11615 were not associated with Ki67 status. Our findings firstly show that the T allele of ERCC1 rs11615 can serve as a predictive biomarker for breast cancer and TNBC. We believe that ERCC1 could serve as a target for personalized treatment of breast cancer, especially for TNBC.
Highlights
Published statistics reveal that breast cancer is the most common cancer diagnosed among females worldwide [1]
The results demonstrated that these lifestyle-related factors may put the breast cancer patients at risk (p
In 2014, the Cyclin D1 (CCND1) A870G GG genotype was found to be infrequent in Taiwanese triple negative breast cancer (TNBC) patients, which may contribute to distinguishing the TNBC patients from other breast cancer patients [36]
Summary
Published statistics reveal that breast cancer is the most common cancer diagnosed among females worldwide [1]. Contribution of ERCC1 genotypes to TNBC risk (TNBC) accounts for 10–20% of all newly diagnosed female breast cancers [2]. Since cells of this cancer lack the three common receptors, estrogen receptor (ER), progesterone receptor (PR), and hormone epidermal growth factor receptor 2 (HER-2), there are as yet no specific clinical drugs or targeting therapies for this kind of breast cancer. TNBC is characterized by high invasiveness, poor prognosis, and high chances of recurrence [3]. The abnormality of gene expression in TNBC patients is another concern of scientists. Given the shortage of targeted treatments for TNBC and its typical properties, the discovery of the biomarkers and medication for TNBC are considered to be in a high priority
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