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Correlations between CYP3A4 polymorphism and susceptibility to breast cancer in Chinese Han population

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Abstract

Background

CYP3A4 is a major enzyme catalyzing the metabolism of endogenous steroids that play an important role in the etiology of carcinogenesis. This study was designed to investigate the contribution of CYP3A4 polymorphism to breast cancer in Chinese Han female population.

Methods

To examine whether variants of CYP3A4 contribute to breast cancer, 5 single-nucleotide polymorphisms (SNPs) of CYP3A4 were genotyped by Sequenom MassARRAY in 267 breast cancer patients and 302 healthy controls. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age.

Results

We found that the TT genotype of CYP3A4*1G (rs2242480) polymorphism was associated with increased risk of breast cancer using the fixed effects model (recessive model: OR = 2.34, p = 0.018). Stratified according to age, CYP3A4*1G increased the risk of breast cancer especially in less than 50-year-old group (codominant model OR = 3.68, p = 0.041; recessive model: OR = 3.55, p = 0.012). Furthermore, TT genotype of rs2242480 was associated with Cerb-B2 positive (recessive model: OR = 2.47, p = 0.025) and stage I/II (recessive model: OR = 2.32, p = 0.041). However, no statistically significant associations in other polymorphisms and haploview analysis were observed.

Conclusions

This study provides an evidence for polymorphism of CYP3A4 gene associated with the development of breast cancer, also a new insight into etiology of breast cancer. However, the underlying mechanism of the CYP3A4 gene in breast cancer is necessary for further study.

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Acknowledgements

This study was funded by Sanming Project of Medicine in Shenzhen (No. SZSM201612021) and Science-Technology Developing Project of Guangdong Province (No. 2017B090904010). We are grateful to the individuals for their participation in this study. We also thank the clinicians and hospital staff who contributed to the sample and data collection for this study. We would also like to thank all participants for this manuscript. Special thanks go to Zhijun Dai (Department of Oncology, The Second Affiliated Hospital, Xi’an Jiaotong University) for the sample and data collection and Bo Xu (Department of Bioinformatics, College of Life Sciences, Northwest Agriculture and Forestry University) for helpful checking our statistical methods.

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Author notes

  1. Xu Liu and Xi Huang cofirst authors.

Authors and Affiliations

  1. Department of Hepato-Pancreato-Biliary Surgery, Peking University Shenzhen Hospital, #1120, Lianhua Road, Futian District, Shenzhen, 518036, Guangdong, China

    Xu Liu & Jikui Liu

  2. Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China

    Xi Huang

  3. Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi′an, 710069, Shaanxi, China

    Shanshan Zhang, Fanglin Niu & Yongri Ouyang

  4. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, #1277, Jiefang Avenue, Jianghan District, Wuhan, 430022, Hubei, China

    Zhexing Shou

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  1. Xu Liu
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Correspondence to Zhexing Shou or Jikui Liu.

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Liu, X., Huang, X., Zhang, S. et al. Correlations between CYP3A4 polymorphism and susceptibility to breast cancer in Chinese Han population. Int J Clin Oncol 24, 179–188 (2019). https://doi.org/10.1007/s10147-018-1346-8

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  • DOI: https://doi.org/10.1007/s10147-018-1346-8

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