Contribution of excision repair cross-complementing group 1 genotypes to triple negative breast cancer risk

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.

Involvement of ERCC1 (rs3212986) and ERCC2 (rs1799793, rs13181) polymorphisms of DNA repair genes in breast cancer occurrence in Burkina Faso

“…In the present study, the results of the association analysis indicated that the ERCC1rs3212986 (C8092A) polymorphism was not associated with breast cancer risk in the study population ( p > .05). The same result was reported in the Taiwanese population in 2018 (Tsai et al, 2018 ), Chinese in 2013 (Yang et al, 2013 ), and American in 2006 (Shen et al, 2006 ). In contrast, a case–control study (872 cases and 671 controls) conducted by Lee et al in the Korean population indicated that the AA mutant genotype of the polymorphism is associated with a risk of breast cancer (Lee et al, 2005 ).…”

A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

“…Moreover, it is well known that cancer stem cells gain the enhanced DNA repair capacity, rendering them resistant to radiation [ 47 ]. Notably, our findings showed that pre-treatment with MPSE mediated down-regulation of DNA repair proteins such as DNA excision repair protein (ERCC5) [ 48 ], neuroepithelial cell-transforming gene 1 protein (NET1) [ 49 ], BRCA2-interacting transcriptional repressor (EMSY) [ 50 ], and junctional adhesion molecule A (F11R), which enhanced the radiosensitivity of breast cancer cells by reducing the formation of cancer stem cells. These findings are consistent with our earlier results (γH2AX), which revealed that the combination treatment of MPSE with IR enhances the efficacy of IR by increasing IR-induced DNA damage and IR-induced cell death.…”

Association of Interleukin-4 Polymorphisms With Breast Cancer in Taiwan

“…The current study was reviewed and approved by the Institutional Review Board of China Medical University Hospital (DMR99-IRB-108). Briefly, a total of 2464 subjects were recruited, including 1,232 female patients diagnosed with breast cancer and exactly the same number of age-matched healthy individuals visiting the China Medical University Hospital, one of the national medical centers in central Taiwan (22)(23)(24). The exclusion criteria for recruiting the healthy controls included any metastatic cancer of any origin, any previous malignancy, and any hereditary or genetic disease.…”