XPF -673C>T variation is associated with the susceptibility to breast cancer
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- Title: XPF -673C>T variation is associated with the susceptibility to breast cancer
- Author: Hongjiao Wua,b,1, Qinqin Songc,1, Zhi Zhangc, Ang Lia, Xiaochao Zhud, Zhenbang Yange, Xuemei Zhanga,b,*
- Publication: Cancer Epidemiology
- Publisher: Elsevier Inc
- Year: 2021
- Language: English
- Pages: 7
- Format: PDF
- File size: 1,560 KB
- DOI: 110.1016/j.canep.2021.102007
- CBID: CBR369
Highlights
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The expression of XPF in breast cancer tissue is higher than that in normal tissue.
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Overexpression of XPF prolongs relapse free survival rate in breast cancer patients.
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XPF – 673TT and XPF 11985GG genotype can reduces the risk of early breast cancer.
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XPF 11985A > G variant can reduce the risk of ERBB2 expression in patients.
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XPF -673C > T variant can reduce XPF expression.
Abstract
Purpose
XPF variations might decrease the DNA repair capacity and further contribute to cancer development. This study aimed to investigate the association of XPF polymorphisms with risk of developing breast cancer.
Methods
TCGA, the Human Protein Atlas and Kaplan-Meier plotter were used to analyze the expression of XPF in breast cancer tissues and its effect on the survival of breast cancer patients. The expression of XPF in breast cancer tissues was detected by qRT-PCR. This case-control study included 467 breast cancer patients and 467 healthy controls. The genotype of genetic variation was detected by polymerase chain reaction restriction fragment length polymorphism. Odds ratios and 95 % confidence intervals were calculated. Correlations between XPF variation and clinicopathological parameters were assessed through Kendall’s Tau-b test. The relationship between XPF gene function variation and XPF gene expression was analyzed by GTEx.
Results
The expression of XPF in breast cancer tissues is higher than that in normal tissues. Breast cancer patients with high XPF expression have a higher relapse free survival rate ( HR = 0.88, 95 % CI = 0.80−0.97), but have no effect on the overall survival rate (logrank P = 0.28). XPF -673C > T variant can reduce the risk of breast cancer patients ( OR = 0.35, 95 % CI = 0.20−0.63 for codominant mode; OR = 0.66, 95 % CI = 0.51−0.85 for dominant model; OR = 0.40, 95 % CI = 0.23−0.70 for recessive model). The XPF 11985 GG genotype reduced the risk of early breast cancer ( OR = 0.49, 95 % CI = 0.24−0.97), but not the risk of advanced breast cancer ( OR = 1.20, 95 % CI = 0.58−2.48). XPF 11985A > G variant can also reduce the risk of ERBB2 expression in patients ( OR = 0.50, 95 % CI = 0.27−0.94). There is no correlation between XPF -673C > T/ XPF 11985A > G variants and ER and PR. XPF -673C > T variant can reduce XPF expression ( P < 0.05).
Conclusions
Genetic variations of XPF gene may affect its expression and the risk of breast cancer in the Chinese population.
1
Introduction
Breast cancer is the most common malignancy and the first leading cause of cancer death in women all over the world [ ]. In China, there are about 268, 600 newly diagnosed breast cancer cases in 2015, which accounting for approximately 15 % of all new cancer cases among women [ ]. To date, many environmental factors, such as pregnancies, breastfeeding, hormone replacement therapy and lifestyle, have been verified to contribute to the risk of breast cancer [ ]. Family history is the most important genetic risk factor, which tripled the risk of breast cancer, especially in the first-degree relatives [ ]. Researchers also demonstrated that inherited genetic variations contributed to breast cancer susceptibility [ ].
Nucleotide excision repair (NER), which removes DNA lesion caused by ultraviolet, chemical carcinogen, and ionizing radiation, is one of the most essential DNA repair systems. NER complex consisting of more than 30 proteins, is responsible for recognizing and repairing damaged DNA [ , ]. NER deficiency may lead to DNA mutation and genomic instability, which further contribute to the development of breast cancer [ , ]. In the process of NER, XPF interacts with ERCC1 to form a structure-specific endonuclease to incise damaged DNA strand [ ]. Researchers also found that XPF genetic variations were associated with the increased risk of various cancers, such as esophageal cancer and gastric cancer [ ]. Study also showed that −673 T allele had a significantly higher promoter activity as compared with -673C allele in lung cancer cells [ ]. In this study, we conducted a case-control study to explore the relationship between XPF polymorphisms (-673C > T and 11985A > G) and the risk of breast cancer in Chinese population.
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