Top

Published in:

01-03-2009 | Epidemiology

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

Authors: Lina Zhang, Lin Gu, Biyun Qian, Xishan Hao, Wei Zhang, Qingyi Wei, Kexin Chen

Published in: Breast Cancer Research and Treatment | Issue 2/2009

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%) (P = 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.

Russo IH, Russo J (1998) Role of hormones in mammary cancer initiation and progression. J Mammary Gland Biol Neoplasia 3(1):49–61PubMedCrossRef

Gomez R, Magana JJ, Cisneros B, Perez-Salazar E, Faugeron S, Veliz D et al (2007) Association of the estrogen receptor alpha gene polymorphisms with osteoporosis in the Mexican population. Clin Genet 72(6):574–581PubMedCrossRef

Schiff R, Massarweh SA, Shou J, Bharwani L, Mohsin SK, Osborne CK (2004) Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance. Clin Cancer Res 10(1 Pt 2):331S–336SPubMedCrossRef

Hopper JL, Hayes VM, Spurdle AB, Chenevix-Trench G, Jenkins MA, Milne RL. et al (2005) A protein-truncating mutation in CYP17A1 in three sisters with early-onset breast cancer. Hum Mutat 26(4):298–302PubMedCrossRef

Setiawan VW, Schumacher FR, Haiman CA, Stram DO, Albanes D, Altshuler D et al (2007) CYP17 genetic variation and risk of breast and prostate cancer from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). Cancer Epidemiol Biomarkers Prev 16(11):2237–2246PubMedCrossRef

Feigelson HS, Shames LS, Pike MC, Coetzee GA, Stanczyk FZ, Henderson BE (1998) Cytochrome P450c17alpha gene (CYP17) polymorphism is associated with serum estrogen and progesterone concentrations. Cancer Res 58(4):585–587PubMed

Maggiolini M, Bonofiglio D, Pezzi V, Carpino A, Marsico S, Rago V et al (2002) Aromatase overexpression enhances the stimulatory effects of adrenal androgens on MCF7 breast cancer cells. Mol Cell Endocrinol 193(1–2):13–18PubMedCrossRef

Ingle JN (2005) Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings. Clin Cancer Res 11(2 Pt 2):900s–905sPubMed

Haiman CA, Hankinson SE, Spiegelman D, Colditz GA, Willett WC, Speizer FE et al (1999) The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer. Cancer Res 59(5):1015–1020PubMed

10.

Ribeiro FS, de Amorim LM, de Almeida Simao T, Mendonca GA, de Moura Gallo CV, Pinto LF (2006) CYP19 (TTTA) n polymorphism and breast cancer risk in Brazilian women. Toxicol Lett 164(1):90–95PubMedCrossRef

11.

Haiman CA, Hankinson SE, Spiegelman D, Brown M, Hunter DJ (2002) No association between a single nucleotide polymorphism in CYP19 and breast cancer risk. Cancer Epidemiol Biomarkers Prev 11(2):215–216PubMed

12.

Kristensen VN, Andersen TI, Lindblom A, Erikstein B, Magnus P, Borresen-Dale AL (1998) A rare CYP19 (aromatase) variant may increase the risk of breast cancer. Pharmacogenetics 8(1):43–48PubMedCrossRef

13.

Hall JM, Couse JF, Korach KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276(40):36869–36872PubMedCrossRef

14.

Boyapati SM, Shu XO, Ruan ZX, Cai Q, Smith JR, Wen W et al (2005) Polymorphisms in ER-alpha gene interact with estrogen receptor status in breast cancer survival. Clin Cancer Res 11(3):1093–1098PubMed

15.

Onland-Moret NC, van Gils CH, Roest M, Grobbee DE, Peeters PH (2005) The estrogen receptor alpha gene and breast cancer risk (The Netherlands). Cancer Causes Control 16(10):1195–1202PubMedCrossRef

16.

Kenealy MR, Flouriot G, Sonntag-Buck V, Dandekar T, Brand H, Gannon F (2000) The 3 ′-untranslated region of the human estrogen receptor alpha gene mediates rapid messenger ribonucleic acid turnover. Endocrinology 141(8):2805–2813PubMedCrossRef

17.

Sowers MR, Jannausch ML, McConnell DS, Kardia SR, Randolph JF Jr (2006) Endogenous estradiol and its association with estrogen receptor gene polymorphisms. Am J Med 119(9 Suppl 1):S16–S22PubMedCrossRef

18.

Lahiri DK, Schnabel B (1993) DNA isolation by a rapid method from human blood samples: effects of MgCl2, EDTA, storage time, and temperature on DNA yield and quality. Biochem Genet 31(7–8):321–328PubMedCrossRef

19.

Ma H, Bernstein L, Pike MC, Ursin G (2006) Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies. Breast Cancer Res 8(4):R43.

20.

Kelsey JL, Gammon MD, John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev 15(1):36–47PubMed

21.

Chakraborty A, Murthy NS, Chintamani C, Bhatnagar D, Mohil RS, Sharma PC et al (2007) CYP17 gene polymorphism and its association with high-risk north Indian breast cancer patients. J Hum Genet 52(2):159–165PubMedCrossRef

22.

Miyoshi Y, Ando A, Ooka M, Shiba E, Taguchi T, Tamaki Y. et al (2003) Association of CYP17 genetic polymorphism with intra-tumoral estradiol concentrations but not with CYP17 messenger RNA levels in breast cancer tissue. Cancer Lett 195(1):81–86PubMedCrossRef

23.

Onland-Moret NC, van Gils CH, Roest M, Grobbee DE, Peeters PH (2005) Cyp17, urinary sex steroid levels and breast cancer risk in postmenopausal women. Cancer Epidemiol Biomarkers Prev 14(4):815–820PubMedCrossRef

24.

Kristensen VN, Harada N, Yoshimura N, Haraldsen E, Lonning PE, Erikstein B et al (2000) Genetic variants of CYP19 (aromatase) and breast cancer risk. Oncogene 19(10):1329–1333PubMedCrossRef

25.

Ali S, Coombes RC (2000) Estrogen receptor alpha in human breast cancer: occurrence and significance. J Mammary Gland Biol Neoplasia 5(3):271–281PubMedCrossRef

26.

Balfe P, McCann A, McGoldrick A, McAllister K, Kennedy M, Dervan P et al (2004) Estrogen receptor alpha and beta profiling in human breast cancer. Eur J Surg Oncol 30(5):469–474PubMedCrossRef

27.

Gold B, Kalush F, Bergeron J, Scott K, Mitra N, Wilson K et al (2004) Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Cancer Res 64(24):8891–8900PubMedCrossRef

Title: Association of genetic polymorphisms of ER-α and the estradiol-synthesizing enzyme genes CYP17 and CYP19 with breast cancer risk in Chinese women
Authors: Lina Zhang
Lin Gu
Biyun Qian
Xishan Hao
Wei Zhang
Qingyi Wei
Kexin Chen
Publication date: 01-03-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-9998-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2009

Programmed Cell Death 4 inhibits breast cancer cell invasion by increasing Tissue Inhibitor of Metalloproteinases-2 expression

The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology

Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERα negative MDA-MB-435 breast cancer model

Utility of metformin in breast cancer treatment, is neoangiogenesis a risk factor?

Molecular profiles of progesterone receptor loss in human breast tumors

Impact, mechanisms, and novel chemotherapy strategies for overcoming resistance to anthracyclines and taxanes in metastatic breast cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer