The CYP19 RS4646 polymorphism IS related to the prognosis of stage I-II and operable stage III breast cancer

Xiying Shao; Yong Guo; Xiaohong Xu; Yabing Zheng; Jiwen Wang; Zhanhong Chen; Jian Huang; Ping Huang; Jufen Cai; Xiaojia Wang

doi:10.1371/journal.pone.0121535

The CYP19 RS4646 polymorphism IS related to the prognosis of stage I-II and operable stage III breast cancer

PLoS One. 2015 Mar 20;10(3):e0121535. doi: 10.1371/journal.pone.0121535. eCollection 2015.

Authors

Xiying Shao¹, Yong Guo², Xiaohong Xu³, Yabing Zheng¹, Jiwen Wang⁴, Zhanhong Chen¹, Jian Huang¹, Ping Huang¹, Jufen Cai¹, Xiaojia Wang¹

Affiliations

¹ Department of Medical Oncology, The Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.
² Department of Oncology, The First Affiliated Hospital of Zhejiang Traditional Chinese Medical University, Hangzhou, Zhejiang Province, China.
³ Clinical laboratory, The Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.
⁴ Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China.

Abstract

Purpose: Aromatase, encoded by the CYP19 gene, catalyzes the final step of the conversion of androgens to estrogens. Given the critical role of CYP19 in estrogen synthesis, the potential influence of CYP19 rs4646 polymorphism on breast cancer survival, deserves further study.

Methods: Genotyping for CYP19 rs4646 variants was performed on 406 Chinese women with stage I-II and operable stage III breast cancer. Associations were evaluated between CYP19 rs4646 genotypes and disease-free survival (DFS).

Results: In premenopausal patients, women who are homozygous for the minor allele (AA) have a longer DFS compared with those carrying the major allele (CC or AC) (87 months versus 48.7 months; Hazard ratio (HR) = 0.56, 95 % CI = 0.318-0.985, P = 0.041). These differences were further demonstrated by a multivariate analysis (HR = 0.456, 95 % CI = 0.249-0.836, P = 0.011). Conversely, the same variant (AA) was estimated to be associated with a poorer DFS in postmenopausal women (AA versus AC or CC: 13.7 months versus 56.3 months; HR = 2.758, 95 % CI = 1.432-5.313, P = 0.002). Furthermore, the differences were confirmed by the COX proportional hazards model (HR = 2.983, 95% CI =1.494-5.955, P = 0.002).

Conclusions: The present study indicates that CYP19 rs4646 polymorphism is related to DFS in early breast cancer and that the prognosis index of the homozygous for the minor allele (AA) may depend on menopause status. The findings are novel, if confirmed, rs4646 genotypes may provide useful information for routine management in breast cancer.

Publication types

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

MeSH terms

Adult
Aged
Aromatase / genetics*
Breast Neoplasms / enzymology
Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Breast Neoplasms / surgery*
Disease-Free Survival
Female
Humans
Middle Aged
Multivariate Analysis
Polymorphism, Single Nucleotide / genetics*
Premenopause / genetics
Prognosis
Young Adult

Substances

Aromatase
CYP19A1 protein, human

Grants and funding

This work was supported by grants from Zhejiang provincial natural science foundation (Y206856,Y2101312, China), Zhejiang provincial medical science and technology program (2010QNA006, 2011RCA011, China), Zhejiang traditional Chinese medicine science and technology program (2013ZB022, 2014ZB019, China), Special fund of Wu Jieping Medical Foundation clinical research (320.670010007, China). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.