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XRCC1 rs1799782 (C194T) polymorphism correlated with tumor metastasis and molecular subtypes in breast cancer

Authors Li Q, Ma R, Zhang M

Received 21 October 2017

Accepted for publication 26 August 2018

Published 28 November 2018 Volume 2018:11 Pages 8435—8444

DOI https://doi.org/10.2147/OTT.S154746

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Qing Li,1 Rong Ma,2 Mei Zhang1

1Department of Breast and Thyroid Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, PR China; 2Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China

Background: Breast cancer, a malignant tumor with its highest incidence in women, affects physical and mental health, and can even be life-threatening. In recent years, its incidence has continued to grow, accompanied by a trend of younger onset. XRCC1 is well known as a DNA-repair gene, and its abnormal expression is related to the occurrence of various malignant tumors.
Methods: In this study, we detected XRCC1 expression and investigated its association with the XRCC1 rs1799782 polymorphism. XRCC1 was overexpressed to investigate its effect on in breast cancer cells. CCK8 and clone formation efficiency assay were used to detect cell proliferation. Transwell assay was performed to confirm cell migration and invasion. Flow cytometry was used to detect cell apoptosis.
Results: In 118 breast cancer samples, CC genotype frequency was 49.15% (58 of 118), CT genotype frequency was 42.37% (50 of 118), and TT genotype frequency was 8.48% (ten of 118). Lymphatic metastasis was associated with a higher frequency of XRCC1 rs1799782 polymorphism (P<0.05), and breast cancer patients with positive PR, HER2, and negative ER had high XRCC1 rs1799782 frequency (P<0.05). Meanwhile, XRCC1 had low expression in breast cancer (74.6%, 88 of 118) and high expression in ER-negative, PR-negative, HER2-positive and Ki67-low-expression patients. XRCC1 rs1799782 may play an important role in the development and metastasis of breast cancer. These results differ from previous studies that did not suggest that rs1799782 is effective in breast cancer. We also investigated the role of XRCC1 in breast cancer progression.
Conclusion: We have proved that XRCC1 can inhibit proliferation and invasion and promote apoptosis of breast cancer cells. XRCC1 expression was regulated by the JNK pathway. We found that the JNK inhibitor SP600125 significantly inhibited the growth of breast cancer cells, and consider it a potential drug for breast cancer.

Keywords:
MCF7, gene expression, proliferation, apoptosis, JNK pathway

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