Estrogen Receptor Alpha Gene Single Nucleotide Polymorphisms, +2464 C/T and -4576A/C, and Breast Cancer Risk, a Hospital-Based Case-Control Study
-
Ali Akbar Amirzargar
,
Maryam Sadr
,
Samira Esmaeili Reykande
,
Elham Mohebbi
,
Mohammad Shirkhoda
,
Majid Mahmoodi
Abstract
Background: Estrogen is a risk factor for the development of breast cancer. The effect of estrogen is primarily mediated by estrogen receptor alpha 1 (ESR1). In this study, we investigated the association between breast cancer risk and the frequency of alleles and genotypes for two ESR1 single nucleotide polymorphisms (SNPs) in breast cancer patients and a healthy control group. Methods: A total of 98 female patients with pathologically confirmed breast cancer and 93 age-matched healthy female controls who were selected from among the visitors of the general hospital were recruited in the study. Two ESR1 candidate polymorphisms; +2464 C/T (rs3020314) and -4576A/C (rs1514348) were selected. The frequency of alleles and genotypes was determined using Quantitative Real-Time PCR assay. Linkage disequilibrium (LD) was assessed for each pair of markers. Using logistic regression, genotype frequencies were estimated as Odds Ratios with 95% confidence intervals. Results: There was no significant difference in the genotype and allele distributions of ESR1 for SNPs +2464 C/T and SNP -4576A/C between patients and controls. The frequency of the ESR1 +2464 T/T genotype in case and control groups was 31.6% vs 29.0%, (OR TT/TC: 1.13, 95%CI: 0.58, 2.20; P = 0.69). The frequency of the +2464C allele was 33.9% vs 35.2%, (OR C/T: 0.94, 95%CI: 0.60, 1.47; P =0.79). The frequency of the ESR1 -4576C/C genotype in case and control groups was 37.75% vs 33.36 %, OR CC/AC: 1.02, 95%CI: 0.51, 1.97; P =0.98). The frequency of the -4576A allele was 36.2% vs 43.6 %, (OR C/A: 0.73, 95%CI: 0.47, 1.13; P =0.14). Conclusion: The results indicated that ESR1 polymorphism does not show any significant association with breast cancer risk among female Iranian adults.
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11. Mosselman S, Polman J, Dijkema R (1996) ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 392(1):49–53.
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17. Wang Y, He Y, Qin Z, et al (2014). Evaluation of functional genetic variants at 6q25.1 and risk of breast cancer in a Chinese population. Breast Cancer Res, 16, 422.
18. Son BH, Kim MK, Yun YM, et al (2015). Genetic polymorphism of ESR1 rs2881766 increases breast cancer risk in Korean women. J Cancer Res Clin Oncol, 141, 633-45.
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20. Onay VU, Briollais L, Knight JA, Shi E, Wang Y, Wells S, et al., SNP-SNP interactions in breast cancer susceptibility. BMC Cancer 2006; 6: 114.
21. Modugno F, Zmuda JM, Potter D, Cai C, Ziv E, Cummings SR, et al., (2005). Association of estrogen receptor alpha polymorphisms with breast cancer risk in older Caucasian women. Int J Cancer. 116(6):984–991.
22. Andersen TI, Heimdal KR, Skrede M, Tveit K, Berg K, Borresen AL (1994). Oestrogen receptor (ESR) polymorphisms and breast cancer susceptibility. Hum Genet 94(6):665–670.
23. Shin A, Kang D, Nishio H, Lee MJ, Park SK, Kim SU, et al (2003) Estrogen receptor alpha gene polymorphisms and breast cancer risk. Breast Cancer Res Treat 80(1):127–131.
24. Wedren S, Lovmar L, Humphreys K, Magnusson C, Melhus H, Syvanen AC, Kindmark A, Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study. Breast Cancer Res 2004; 6: R437-449.
25. Lipphardt MF, Deryal M, Ong MF, Schmidt W, Mahlknecht U. ESR1 single nucleotide polymorphisms predict breast cancer susceptibility in the central European Caucasian population. Int J Clin Exp Med. 2013;6(4):282-8.
26. Mavaddat N, Dunning AM, Ponder BA, Easton DF, Pharoah PD. Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer. Cancer Epidemiol Biomarkers Prev 2009; 18: 255-259.
27. Roe B, Crabtree J, and Khan AS (1995) Methods for DNA isolation. Part III. Protocols for recombinant DNA isolation, cloning, and sequencing [Internet edition]. University of Oklahoma, Norman, OK. 2488-98.
28. Kang HJ, Kim SW, Kim HJ, et al. Polymorphisms in the estrogen receptor-alpha gene and breast cancer risk. Cancer Lett 2002;178:175–80.
29. Vandevord PJ, Wooley PH, Darga LL, Severson RK, Wu B, Nelson DA (2006) Genetic determinants of bone mass do not relate with breast cancer risk in US white and African American women. Breast Cancer Res Treat 100(1):103–107.
30. Cai Q, Shu XO, Jin F, Dai Q, Wen W, Cheng JR, Gao YT, Zheng W (2003) Genetic polymorphisms in the estrogen receptor alpha gene and risk of breast cancer: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev 12(9):853–859.
31. Cox A, Dunning AM, Garcia-Closas M, Balasubramanian A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 2007; 39: 352-358.
32. Dunning AM, Healey CS, Baynes C, Maia AT, Scollen S, Vega A, Rodriguez R, Barbosa-Morais Association of ESR1 gene tagging SNPs with breast cancer risk. Hum Mol Genet 2009; 18:1131-39.
2. Porter P (2008) "Westernizing" women's risks? Breast cancer in lower-income countries. N Engl J Med 358(3):213-6.
3. MOHEBBI, Elham et al. Iran Cancer Statistics in 2012 and Projection of Cancer Incidence by 2035. Basic & Clinical Cancer Research, [S.l.], v. 9, n. 3, p. 3-22, jan. 2018.
4. Ambrosone CB, Hong CC, Goodwin PJ. Host Factors and Risk of Breast Cancer Recurrence: Genetic, Epigenetic and Biologic Factors and Breast Cancer Outcomes. Adv Exp Med Biol. 2015;862:143-53.4.
5. Rudolph A, Chang-Claude J, Schmidt MK. Gene-environment interaction and risk of breast cancer. Br J Cancer. 2016 19;114(2):125-33.
6. Balmain A, Gray J, Ponder B (2003) The genetics and genomics of cancer. Nat Genet 33: 238-44
7. Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24(14): 2137-50.
8. Cheskis BJ, Greger JG, Nagpal S, Freedman LP. Signaling by estrogens. J Cell Physiol. 2007;213(3):610-7.
9. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS: Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ER beta) messenger ribonucleic acid in the wild-type and ER-alpha knockout mouse. Endocrinology 1997, 138:4613-4621.
10. Nilsson M, Dahlman-Wright K, Gustafsson JA. Nuclear receptors in disease: the oestrogen receptors. Essays Biochem 2004;40:157–67.
11. Mosselman S, Polman J, Dijkema R (1996) ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 392(1):49–53.
12. Lin CY, Ström A, Vega VB, Kong SL, Yeo AL, Thomsen JS, et al. (2004). "Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells". Genome Biol. 5 (9): R66.
13. Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, et al., Estrogen receptors: how do they signal and what are their targets. Physiol Rev 2007, 87:905-931.
14. Thomas C, Gustafsson JA: The different roles of ER subtypes in cancer biology and therapy. Nat Rev Cancer 2011, 11:597–608.
15. Sommer S, Fuqua SA (2001). Estrogen receptor and breast cancer. Semin Cancer Biol, 11, 339-52.
16. Fernandez LP, Milne RL, Barroso E, Cuadros M, Arias JI, Ruibal A, Benitez J and Ribas G. Estrogen and progesterone receptor gene polymorphisms and sporadic breast cancer risk: a Spanish case-control study. Int J Cancer 2006; 119: 467-471.
17. Wang Y, He Y, Qin Z, et al (2014). Evaluation of functional genetic variants at 6q25.1 and risk of breast cancer in a Chinese population. Breast Cancer Res, 16, 422.
18. Son BH, Kim MK, Yun YM, et al (2015). Genetic polymorphism of ESR1 rs2881766 increases breast cancer risk in Korean women. J Cancer Res Clin Oncol, 141, 633-45.
19. Einarsdottir, K., Darabi, H., Li, Y., Low, Y-L., Li, Y-Q., Bonnard, C., Sjolander, A., Czene, K., Wedren, S., Liu, E.T. et al. (2008) ESR1 and EGF genetic variation in relation to breast cancer risk and survival. Breast Cancer Res., 10 (1), R15.
20. Onay VU, Briollais L, Knight JA, Shi E, Wang Y, Wells S, et al., SNP-SNP interactions in breast cancer susceptibility. BMC Cancer 2006; 6: 114.
21. Modugno F, Zmuda JM, Potter D, Cai C, Ziv E, Cummings SR, et al., (2005). Association of estrogen receptor alpha polymorphisms with breast cancer risk in older Caucasian women. Int J Cancer. 116(6):984–991.
22. Andersen TI, Heimdal KR, Skrede M, Tveit K, Berg K, Borresen AL (1994). Oestrogen receptor (ESR) polymorphisms and breast cancer susceptibility. Hum Genet 94(6):665–670.
23. Shin A, Kang D, Nishio H, Lee MJ, Park SK, Kim SU, et al (2003) Estrogen receptor alpha gene polymorphisms and breast cancer risk. Breast Cancer Res Treat 80(1):127–131.
24. Wedren S, Lovmar L, Humphreys K, Magnusson C, Melhus H, Syvanen AC, Kindmark A, Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study. Breast Cancer Res 2004; 6: R437-449.
25. Lipphardt MF, Deryal M, Ong MF, Schmidt W, Mahlknecht U. ESR1 single nucleotide polymorphisms predict breast cancer susceptibility in the central European Caucasian population. Int J Clin Exp Med. 2013;6(4):282-8.
26. Mavaddat N, Dunning AM, Ponder BA, Easton DF, Pharoah PD. Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer. Cancer Epidemiol Biomarkers Prev 2009; 18: 255-259.
27. Roe B, Crabtree J, and Khan AS (1995) Methods for DNA isolation. Part III. Protocols for recombinant DNA isolation, cloning, and sequencing [Internet edition]. University of Oklahoma, Norman, OK. 2488-98.
28. Kang HJ, Kim SW, Kim HJ, et al. Polymorphisms in the estrogen receptor-alpha gene and breast cancer risk. Cancer Lett 2002;178:175–80.
29. Vandevord PJ, Wooley PH, Darga LL, Severson RK, Wu B, Nelson DA (2006) Genetic determinants of bone mass do not relate with breast cancer risk in US white and African American women. Breast Cancer Res Treat 100(1):103–107.
30. Cai Q, Shu XO, Jin F, Dai Q, Wen W, Cheng JR, Gao YT, Zheng W (2003) Genetic polymorphisms in the estrogen receptor alpha gene and risk of breast cancer: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev 12(9):853–859.
31. Cox A, Dunning AM, Garcia-Closas M, Balasubramanian A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 2007; 39: 352-358.
32. Dunning AM, Healey CS, Baynes C, Maia AT, Scollen S, Vega A, Rodriguez R, Barbosa-Morais Association of ESR1 gene tagging SNPs with breast cancer risk. Hum Mol Genet 2009; 18:1131-39.
| Files | ||
| Issue | Vol 11 No 2 (2019) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v11i2.1655 | |
| Keywords | ||
| Estradiol receptor Single nucleotide polymorphism Breast neoplasm Association study | ||
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How to Cite
1.
Amirzargar AA, Sadr M, Esmaeili Reykande S, Mohebbi E, Shirkhoda M, Mahmoodi M. Estrogen Receptor Alpha Gene Single Nucleotide Polymorphisms, +2464 C/T and -4576A/C, and Breast Cancer Risk, a Hospital-Based Case-Control Study. Basic Clin Cancer Res. 2019;11(2):84-89.
