No Association between Estrogen Receptor-Β Rs4986938 and Cancer Risk: A Systematic Review and Meta-Analysis
Abstract
Background: The association between estrogen receptor-β (ESR2) rs4986938 polymorphism and the risk of various types of cancer have been investigated in previous studies. However, the results remained disputable. Here, we conducted a meta-analysis to investigate the association between ESR2 rs4986938 polymorphism and the risk of cancer.
Methods: We searched for relevant articles collected by the PubMed, EMBASE, and Cochrane library up to March 30, 2018. The association was assessed using Odds ratios (ORs) and 95% confidence intervals (CIs).
Results: The meta-analysis involved a total of 23 studies in 20 papers, including 24,334 cases and 31,707 controls. No significant association was detected between the rs4986938 polymorphism and cancer risk in the additive model (A compared with G: OR=0.97, 95% CI=0.92-1.02, P=0.20), dominant model (AA+AG compared with GG: OR=0.96, 95% CI=0.93-1.03, P=1.00), recessive model (AA compared with AG + GG: OR=0.94, 95% CI=0.86-1.03, P=0.18), heterozygous model (AG compared with GG: OR=0.97, 95% CI=0.94-1.01, P=0.14), and homozygous model (AA compared with GG: OR=0.96, 95% CI=0.87-1.06, P=0.39). Results of subgroup analysis stratified by ethnicity and cancer types further validated the results.
Conclusion: We found no evidence of an association between rs4986938 and the risk of overall cancer.
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2. Ingles S A, Ross R K, Yu M C, et al (1997). Association of prostate cancer risk with genetic polymorphisms in vitamin D re-ceptor and androgen receptor. J Natl Cancer Inst, 89(2): 166-170.
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8. Chae Y K, Huang H, Strickland P, et al (2009). Genetic polymorphisms of estro-gen receptors alpha and beta and the risk of developing prostate cancer. PloS One, 4(8): e6523.
9. Lu X, Yamano Y, Takahashi H, et al (2015). Associations between estrogen receptor genetic polymorphisms, smoking status, and prostate cancer risk: a case-control study in Japanese men. Environ Health Prev Med, 20(5): 332-337.
10. Ghali R M, Al-Mutawa M A, Al-Ansari A K, et al (2018). Differential association of ESR1 and ESR2 gene variants with the risk of breast cancer and associated fea-tures: A case-control study. Gene, 651: 194-199.
11. Rezende L M, Marson F A L, Lima C S P, et al (2017). Variants of estrogen receptor alpha and beta genes modify the severity of sporadic breast cancer. Gene, 608: 73-78.
12. Levine A J, Ihenacho U, Lee W, et al (2012). Genetic variation in insulin pathway genes and distal colorectal adenoma risk. Int J Colorectal Dis, 27(12): 1587-1595.
13. Paulus J K, Zhou W, Kraft P, et al. (2011). Haplotypes of estrogen receptor-beta and risk of non-small cell lung cancer in women. Lung Cancer, 71(3): 258-263.
14. Cox D G, Bretsky P, Kraft P, et al (2008). Haplotypes of the estrogen receptor beta gene and breast cancer risk. Int J Cancer, 122(2): 387-392.
15. Gallicchio L, Berndt S, Mcsorley M, et al (2006). Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk of developing breast cancer among a cohort of women with benign breast disease. BMC Cancer, 6: 1-11.
16. Chen Y C, Kraft P, Bretsky P, et al (2007). Sequence Variants of Estrogen Receptor and Risk of Prostate Cancer in the Na-tional Cancer Institute Breast and Pros-tate Cancer Cohort Consortium. Cancer Epidemiol Biomarkers Prev, 16(10): 1973-1981.
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18. Forsti A, Zhao C, Israelsson E, et al (2003). Polymorphisms in the estrogen receptor beta gene and risk of breast cancer: no association. Breast Cancer Res Treat, 79(3): 409-413.
19. Sainz J, Rudolph A, Hein R, et al (2011). As-sociation of genetic polymorphisms in ESR2, HSD17B1, ABCB1, and SHBG genes with colorectal cancer risk. Endocr Relat Cancer, 18(2): 265-276.
20. MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk (2010). Polymorphisms in genes of the steroid receptor superfamily modify postmenopausal breast cancer risk asso-ciated with menopausal hormone thera-py. Int J Cancer, 126: 2935-2946.
21. Lim WY, Chen Y, Chuah KL, et al (2012). Female reproductive factors, gene poly-morphisms in the estrogen metabolism pathway, and risk of lung cancer in Chi-nese women. Am J Epidemiol, 175(6): 492-503.
22. Safarinejad MR, Safarinejad S, Shafiei N, et al (2012). Estrogen receptors alpha (rs2234693 and rs9340799), and beta (rs4986938 and rs1256049) genes poly-morphism in prostate cancer: evidence for association with risk and histopatho-logical tumor characteristics in Iranian men. Mol Carcinog, 51 Suppl 1: E104-E117.
23. Park SK, Andreotti G, Rashid A, et al (2010). Polymorphisms of estrogen receptors and risk of biliary tract cancers and gall-stones: a population-based study in Shanghai, China. Carcinogenesis, 31(5): 842-846.
24. Nicolaiew N, Cancel-Tassin G, Azzouzi A R, et al (2008). Association between estrogen and androgen receptor genes and pros-tate cancer risk. Eur J Endocrinol, 160(1): 101-106.
25. Surekha D, Sailaja K, Rao DN, et al (2009). Oestrogen receptor beta (ERbeta) poly-morphism and its influence on breast cancer risk. J Genet, 88(2): 261-266.
26. Burns KA, Korach KS (2012). Estrogen re-ceptors and human disease: An update. Arch Toxicol, 86(10): 1491-1504.
27. Wenkai Xia, Tianyi Wang, Dong Sun, et al (2016). Association of estrogen receptor-beta (ESR2) polymorphism and cancer risk: a meta-analysis. Eur J Gynaecol Oncol, 37(4): 530-538.
28. Torre LA, Siegel RL, Ward EM, Jemal A (2016). Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev, 25(1): 16-27.
29. Hsiao WC, Young KC, Lin SL, et al (2004). Estrogen receptor-alpha polymorphism in a Taiwanese clinical breast cancer pop-ulation: a case-control study. Breast Cancer Res, 6(3): R180-R186.
30. Anghel A, Narita D, Seclaman E, et al (2010). Estrogen receptor alpha poly-morphisms and the risk of malignancies. Pathol Oncol Res, 16(4): 485-496.
31. Akisik E, Dalay N (2004). Estrogen receptor codon 594 and HER2 codon 655 poly-morphisms and breast cancer risk. Exp Mol Pathol, 76(3): 260-263.
32. Milne RL, Antoniou AC (2011). Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers. Ann Oncol, 22(Suppl. 1): i11-i17.
2. Ingles S A, Ross R K, Yu M C, et al (1997). Association of prostate cancer risk with genetic polymorphisms in vitamin D re-ceptor and androgen receptor. J Natl Cancer Inst, 89(2): 166-170.
3. Menasce L P, White G R, Harrison C J, et al (1993). Localization of the estrogen re-ceptor locus (ESR) to chromosome 6q25.1 by FISH and a simple post-FISH banding technique. Genomics, 17(1): 263-265.
4. Enmark E, Pelto-Huikko M, Grandien K, et al (1997). Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab, 82(12): 4258-4265.
5. Ashton K A, Proietto A, Otton G, et al (2009). Estrogen receptor polymor-phisms and the risk of endometrial can-cer. BJOG, 116(8): 1053-1061.
6. Maguire P, Margolin S, Skoglund J, et al (2005). Estrogen receptor beta (ESR2) polymorphisms in familial and sporadic breast cancer. Breast Cancer Res Treat, 94(2): 145-152.
7. Yu K, Rao N, Chen A, et al. (2011) A sys-tematic review of the relationship be-tween polymorphic sites in the estrogen receptor-beta (ESR2) gene and breast cancer risk. Breast Cancer Res Treat, 126(1): 37-45.
8. Chae Y K, Huang H, Strickland P, et al (2009). Genetic polymorphisms of estro-gen receptors alpha and beta and the risk of developing prostate cancer. PloS One, 4(8): e6523.
9. Lu X, Yamano Y, Takahashi H, et al (2015). Associations between estrogen receptor genetic polymorphisms, smoking status, and prostate cancer risk: a case-control study in Japanese men. Environ Health Prev Med, 20(5): 332-337.
10. Ghali R M, Al-Mutawa M A, Al-Ansari A K, et al (2018). Differential association of ESR1 and ESR2 gene variants with the risk of breast cancer and associated fea-tures: A case-control study. Gene, 651: 194-199.
11. Rezende L M, Marson F A L, Lima C S P, et al (2017). Variants of estrogen receptor alpha and beta genes modify the severity of sporadic breast cancer. Gene, 608: 73-78.
12. Levine A J, Ihenacho U, Lee W, et al (2012). Genetic variation in insulin pathway genes and distal colorectal adenoma risk. Int J Colorectal Dis, 27(12): 1587-1595.
13. Paulus J K, Zhou W, Kraft P, et al. (2011). Haplotypes of estrogen receptor-beta and risk of non-small cell lung cancer in women. Lung Cancer, 71(3): 258-263.
14. Cox D G, Bretsky P, Kraft P, et al (2008). Haplotypes of the estrogen receptor beta gene and breast cancer risk. Int J Cancer, 122(2): 387-392.
15. Gallicchio L, Berndt S, Mcsorley M, et al (2006). Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk of developing breast cancer among a cohort of women with benign breast disease. BMC Cancer, 6: 1-11.
16. Chen Y C, Kraft P, Bretsky P, et al (2007). Sequence Variants of Estrogen Receptor and Risk of Prostate Cancer in the Na-tional Cancer Institute Breast and Pros-tate Cancer Cohort Consortium. Cancer Epidemiol Biomarkers Prev, 16(10): 1973-1981.
17. Iwasaki M, Hamada G S, Nishimoto I N, et al (2009). Isoflavone, polymorphisms in estrogen receptor genes and breast can-cer risk in case-control studies in Japa-nese, Japanese Brazilians and non-Japanese Brazilians. Cancer Sci, 100(5): 927-933.
18. Forsti A, Zhao C, Israelsson E, et al (2003). Polymorphisms in the estrogen receptor beta gene and risk of breast cancer: no association. Breast Cancer Res Treat, 79(3): 409-413.
19. Sainz J, Rudolph A, Hein R, et al (2011). As-sociation of genetic polymorphisms in ESR2, HSD17B1, ABCB1, and SHBG genes with colorectal cancer risk. Endocr Relat Cancer, 18(2): 265-276.
20. MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk (2010). Polymorphisms in genes of the steroid receptor superfamily modify postmenopausal breast cancer risk asso-ciated with menopausal hormone thera-py. Int J Cancer, 126: 2935-2946.
21. Lim WY, Chen Y, Chuah KL, et al (2012). Female reproductive factors, gene poly-morphisms in the estrogen metabolism pathway, and risk of lung cancer in Chi-nese women. Am J Epidemiol, 175(6): 492-503.
22. Safarinejad MR, Safarinejad S, Shafiei N, et al (2012). Estrogen receptors alpha (rs2234693 and rs9340799), and beta (rs4986938 and rs1256049) genes poly-morphism in prostate cancer: evidence for association with risk and histopatho-logical tumor characteristics in Iranian men. Mol Carcinog, 51 Suppl 1: E104-E117.
23. Park SK, Andreotti G, Rashid A, et al (2010). Polymorphisms of estrogen receptors and risk of biliary tract cancers and gall-stones: a population-based study in Shanghai, China. Carcinogenesis, 31(5): 842-846.
24. Nicolaiew N, Cancel-Tassin G, Azzouzi A R, et al (2008). Association between estrogen and androgen receptor genes and pros-tate cancer risk. Eur J Endocrinol, 160(1): 101-106.
25. Surekha D, Sailaja K, Rao DN, et al (2009). Oestrogen receptor beta (ERbeta) poly-morphism and its influence on breast cancer risk. J Genet, 88(2): 261-266.
26. Burns KA, Korach KS (2012). Estrogen re-ceptors and human disease: An update. Arch Toxicol, 86(10): 1491-1504.
27. Wenkai Xia, Tianyi Wang, Dong Sun, et al (2016). Association of estrogen receptor-beta (ESR2) polymorphism and cancer risk: a meta-analysis. Eur J Gynaecol Oncol, 37(4): 530-538.
28. Torre LA, Siegel RL, Ward EM, Jemal A (2016). Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev, 25(1): 16-27.
29. Hsiao WC, Young KC, Lin SL, et al (2004). Estrogen receptor-alpha polymorphism in a Taiwanese clinical breast cancer pop-ulation: a case-control study. Breast Cancer Res, 6(3): R180-R186.
30. Anghel A, Narita D, Seclaman E, et al (2010). Estrogen receptor alpha poly-morphisms and the risk of malignancies. Pathol Oncol Res, 16(4): 485-496.
31. Akisik E, Dalay N (2004). Estrogen receptor codon 594 and HER2 codon 655 poly-morphisms and breast cancer risk. Exp Mol Pathol, 76(3): 260-263.
32. Milne RL, Antoniou AC (2011). Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers. Ann Oncol, 22(Suppl. 1): i11-i17.
| Files | ||
| Issue | Vol 48 No 5 (2019) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v48i5.1791 | |
| Keywords | ||
| ESR2 Single nucleotide polymorphism Cancer risk | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
LI Z, YANG X, ZHANG R, LI B, ZHANG D, LI Q, XIONG Y. No Association between Estrogen Receptor-Β Rs4986938 and Cancer Risk: A Systematic Review and Meta-Analysis. Iran J Public Health. 2019;48(5):784-795.
