Polymorphisms of Satellite DNA CYP19 Gene and its Association with Increased Risk of Breast Cancer in Isfahan, Iran

Document Type : Original Article (s)

Authors

1 Student, Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran

2 Assistant Professor, Department of Radiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Assistant Professor, Department of Cellular and Molecular Biology, School of Sciences, University of Isfahan, Isfahan, Iran

Abstract

Background: Aromatase is a key enzyme in the synthesis of estrogen. This enzyme is encoded by the cytochrome P-450 (CYP19) gene. Overexposure of cells to estrogen causes breast carcinoma and breast cancer patients show a higher level of aromatase expression. The purpose of this study was to investigate polymorphism of the CYP19 intron 4 (TTTA)n among breast cancer patients and healthy individuals, and its correlation to risk of breast cancer.Methods: This study was a case-control study on 420 patients and 432 control women. DNA was extracted from the blood of the study subjects, and then the sequence was amplified by the polymerase chain reaction (PCR) technique. Thereafter, the number and sequence of TTTA was measured by electrophoresis in Polyacrylamide gel.Findings: The results of this study show that IGF-I gene allele distribution in the population of Isfahan varies between 7-13 repetitions. The most common allele in both controls and cases was (TTTA)7-TCT with frequencies of 34.3% and 34.8%, respectively.Conclusion: The results of the current study show that the frequency distribution of 10 TTTA repeats is higher in the controls (2.3%) than in patients (1.4%). In other words, not only does 10 TTA not increase the rate of breast cancer, but it may even cause people with this allele to be more resistant to cancer.

Keywords

References

  1. Aronson K. Alcohol: a recently identified risk factor for breast cancer. CMAJ 2003; 168(9): 1147-8.
  2. Yavari P, Mosavizadeh M, Sadrol-Hefazi B, Mehrabi Y. Reproductive characteristics and the risk of breast cancer--a case-control study in Iran. Asian Pac J Cancer Prev 2005; 6(3): 370-5.
  3. Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, et al. Breast cancer in Iran: an epidemiological review. Breast J 2007; 13(4): 383-91.
  4. Figer A, Karasik YP, Baruch RG, Chetrit A, Papa MZ, Sade RB, et al. Insulin-like growth factor I polymorphism and breast cancer risk in Jewish women. Isr Med Assoc J 2002; 4(10): 759-62.
  5. Toda K, Terashima M, Kawamoto T, Sumimoto H, Yokoyama Y, Kuribayashi I, et al. Structural and functional characterization of human aromatase P-450 gene. Eur J Biochem 1990; 193(2): 559-65.
  6. Bulun SE, Simpson ER. Regulation of aromatase expression in human tissues. Breast Cancer Res Treat 1994; 30(1): 19-29.
  7. Ma CX, Adjei AA, Salavaggione OE, Coronel J, Pelleymounter L, Wang L, et al. Human aromatase: gene resequencing and functional genomics. Cancer Res 2005; 65(23): 11071-82.
  8. Baxter SW, Choong DY, Eccles DM, Campbell IG. Polymorphic variation in CYP19 and the risk of breast cancer. Carcinogenesis 2001; 22(2): 347-9.
  9. Kristensen VN, Andersen TI, Lindblom A, Erikstein B, Magnus P, Borresen-Dale AL. A rare CYP19 (aromatase) variant may increase the risk of breast cancer. Pharmacogenetics 1998; 8(1): 43-8.
  10. Miyoshi Y, Iwao K, Ikeda N, Egawa C, Noguchi S. Breast cancer risk associated with polymorphism in CYP19 in Japanese women. Int J Cancer 2000; 89(4): 325-8.
  11. Ribeiro FS, de Amorim LM, de Almeida ST, Mendonca GA, de Moura Gallo CV, Pinto LF. CYP19 (TTTA)n polymorphism and breast cancer risk in Brazilian women. Toxicol Lett 2006; 164(1): 90-5.
  12. Tsuchiya N, Wang L, Suzuki H, Segawa T, Fukuda H, Narita S, et al. Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer. J Clin Oncol 2006; 24(13): 1982-9.
  13. Probst-Hensch NM, Ingles SA, Diep AT, Haile RW, Stanczyk FZ, Kolonel LN, et al. Aromatase and breast cancer susceptibility. Endocr Relat Cancer 1999; 6(2): 165-73.
  14. Okobia MN, Bunker CH, Zmuda JM, Ezeome ER, Anyanwu SN, Uche EE, et al. Simple tandem repeat (TTTA)n polymorphism in CYP19 (aromatase) gene and breast cancer risk in Nigerian women. J Carcinog 2006; 5: 12.
  15. Healey CS, Dunning AM, Durocher F, Teare D, Pharoah PD, Luben RN, et al. Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk. Carcinogenesis 2000; 21(2): 189-93.
  16. Haiman CA, Hankinson SE, Spiegelman D, De V, I, Colditz GA, Willett WC, et al. A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk. Int J Cancer 2000; 87(2): 204-10.
  17. Ahsan H, Whittemore AS, Chen Y, Senie RT, Hamilton SP, Wang Q, et al. Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study. Breast Cancer Res 2005; 7(1): R71-R81.
Journal of Isfahan Medical School
Volume 29, Issue 162 - Serial Number 162
September and October 2012
Pages 1937-1944

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History

  • Receive Date: 11 June 2011
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

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