Breast Cancer Research and Treatment

, Volume 114, Issue 2, pp 327–338

Association of genetic polymorphisms of ER-α and the estradiol-synthesizing enzyme genes CYP17 and CYP19 with breast cancer risk in Chinese women

Epidemiology

DOI: 10.1007/s10549-008-9998-0

Cite this article as:
Zhang, L., Gu, L., Qian, B. et al. Breast Cancer Res Treat (2009) 114: 327. doi:10.1007/s10549-008-9998-0

Abstract

Estrogen plays a role in breast cancer development, and genetic polymorphisms in estrogen receptor gene ER-α and genes regulating estrogen biosynthesis and metabolisms are associated with the risk of breast cancer in women in western countries. Therefore, we hypothesized that SNPs in ER-α and other estrogen-metabolizing genes contribute to breast cancer risk in Chinese women. In this study, we genotyped polymorphisms in the regulatory regions of ER-α (rs3798577) and other two estrogen-metabolizing enzyme genes CYP17 (rs743572) and CYP19 (rs10046) among 300 breast cancer cases and 390 controls in a Chinese population. Crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses to estimate breast cancer risk associated with these polymorphisms. We found that the T allele frequency of ER-α was significantly higher in cases (59.8%) than controls (54.5%) (= 0.047), but no significant difference was found in the genotype distribution. However, postmenopausal breast cancer risk was associated with the CYP17 TC genotype (aOR = 1.77, 95% CI = 1.11–2.83) compared with the TT genotype. The CYP19 variant TC + TT genotypes were associated with both overall cancer risk (TT + TC vs. TT aOR = 1.73, 95% CI = 1.13–2.65) and premenopausal cancer risk (TT + TC vs. TT aOR = 1.78, 95% CI = 1.03–3.09), particularly for ER +/PR + tumors. Furthermore, there were joint effects between CYP19 T and ER-α T varint genotypes (aOR = 1.67, 95% CI = 1.03–2.69 for CYP19 TC + TT vs. CC among ER-α T variant carriers) and between CYP19 T and CYP17 C variant genotypes (aOR = 1.77, 95% CI = 1.11–2.83 for CYP19 TC + TT vs. CC among CYP17 variant C carriers). This study provides evidence that polymorphisms CYP17 rs743572, CYP19 rs10046 and ER-α rs3798577 are associated with breast cancer risk among Chinese women.

Keywords

Case-control studyEstradiol-synthesizing enzymeSusceptible genotypeMolecular epidemiologyPolymorphism

Abbreviations

CYP17

The cytochrome P450c17α enzyme gene

CYP19

Aromatase gene

ER-α

Estrogen receptor α gene

CI

Confidence interval

OR

Odds ratio

SNP

Single nucleotide polymorphism

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  1. 1.Departments of Breast Oncology/SurgeryTianjin Medical University Cancer Institute and HospitalTianjinPeople’s Republic of China
  2. 2.Epidemiology and BiostatisticsTianjin Medical University Cancer Institute and HospitalTianjinPeople’s Republic of China
  3. 3.Departments of PathologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  4. 4.EpidemiologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA