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

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

Xiying Shao  1 , Yong Guo  2 , Xiaohong Xu  3 , Yabing Zheng  1 , Jiwen Wang  4 , Zhanhong Chen  1 , Jian Huang  1 , Ping Huang  1 , Jufen Cai  1 , Xiaojia Wang  1
Affiliations

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

Xiying Shao et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Survival curves for the total patients.
a. Disease-free survival of the patients grouped according to CYP19 rs4646 genotypes (CC vs AC vs AA). b. Disease-free survival of the patients grouped by CYP19 rs4646 genotypes (CC vs AC + AA). c. Disease-free survival of the patients subgrouped according to CYP19 rs4646 genotypes (AC+CC vs AA).
Fig 2
Fig 2. Survival curves for the premenopausal patients.
a. Disease-free survival of the premenopausal women stratified by CYP19 rs4646 genotypes (CC vs AC vs AA). b. Disease-free survival of the premenopausal women grouped according to CYP19 rs4646 genotypes (AA vs AC + CC).
Fig 3
Fig 3. Survival curves for the postmenopausal patients.
a. Disease-free survival of the postmenopausal women grouped by CYP19 rs4646 genotypes (CC vs AC vs AA). b. Disease-free survival of the postmenopausal women stratified by CYP19 rs4646 genotypes (AA vs AC + CC).
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