XPF -673C>T variation is associated with the susceptibility to breast cancer

Hongjiao Wu; Qinqin Song; Zhi Zhang; Ang Li; Xiaochao Zhu; Zhenbang Yang; Xuemei Zhang

doi:10.1016/j.canep.2021.102007

XPF -673C>T variation is associated with the susceptibility to breast cancer

Cancer Epidemiol. 2021 Oct:74:102007. doi: 10.1016/j.canep.2021.102007. Epub 2021 Aug 17.

Authors

Hongjiao Wu¹, Qinqin Song², Zhi Zhang³, Ang Li⁴, Xiaochao Zhu⁵, Zhenbang Yang⁶, Xuemei Zhang⁷

Affiliations

¹ Department of Epidemiology, School of Public Health, North China University of Science and Technology, Tangshan, 063210, China; Department of Molecular Genetics, College of Life Science, North China University of Science and Technology, Tangshan, 063210, China. Electronic address: whj1838074359@163.com.
² Department of Chemotherapy and Radiotherapy, Affiliated Tangshan Gongren Hospital, North China University of Science and Technology, Tangshan, 063000, China. Electronic address: 1003890611@qq.com.
³ Department of Chemotherapy and Radiotherapy, Affiliated Tangshan Gongren Hospital, North China University of Science and Technology, Tangshan, 063000, China. Electronic address: zhi1969@163.com.
⁴ Department of Epidemiology, School of Public Health, North China University of Science and Technology, Tangshan, 063210, China. Electronic address: woainiang521@126.com.
⁵ Department of Thyroid and Breast Surgery, The First Hospital of Suqian, Suqian, 223812, China. Electronic address: Zhuxc05206@126.com.
⁶ Hebei Key Laboratory of Basic Medicine for Chronic Disease, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China. Electronic address: bzy108@126.com.
⁷ Department of Epidemiology, School of Public Health, North China University of Science and Technology, Tangshan, 063210, China; Department of Molecular Genetics, College of Life Science, North China University of Science and Technology, Tangshan, 063210, China. Electronic address: zhangxuemei@ncst.edu.cn.

PMID: 34416547
DOI: 10.1016/j.canep.2021.102007

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/XPF11985A > 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.

Keywords: Breast cancer; Genetic variation; Single nucleotide polymorphism; XPF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / genetics
Case-Control Studies
DNA-Binding Proteins* / genetics
Female
Genetic Predisposition to Disease
Genotype
Humans
Polymorphism, Single Nucleotide

Substances

DNA-Binding Proteins
xeroderma pigmentosum group F protein