- Volume 16 Issue 5
DOI QR Code
Association between GSTP1 Genotypes and Hormone Receptor Phenotype in Invasive Ductal Carcinomas of Breast
- Khabaz, Mohamad Nidal (Department of Pathology, Rabigh Faculty of Medicine, King Abdulaziz University) ;
- Gari, Mamdooh Abdullah (Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University) ;
- Al-Maghrabi, Jaudah Ahmed (Department of Pathology, Faculty of Medicine, King Abdulaziz University) ;
- Nedjadi, Taoufik (King Fahd Medical Research Centre, King Abdulaziz University) ;
- Bakarman, Marwan (Department of Family and Community Medicine, Rabigh Faculty of Medicine, King Abdulaziz University)
- Published : 2015.03.18
Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance.
Supported by : King Abdulaziz University (KAU)
- Aguiar ES, Giacomazzi J, Schmidt AV, et al (2012). GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening. Rev Bras Epidemiol, 15, 246-255. https://doi.org/10.1590/S1415-790X2012000200002
- Al-Eid HS, Garcia AD (2012). Cancer incidence report Saudi Arabia 2009. Saudi cancer registry, ministry of health, Kingdom of Saudi Arabia.
- Allan JM, Wild CP, Rollinson S, et al (2001). Polymorphism in Glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. PNAS, 98, 11592-7. https://doi.org/10.1073/pnas.191211198
- Arun BK, Granville LA, Yin G, et al (2010). Glutathione-stransferase- pi expression in early breast cancer: association with outcome and response to chemotherapy. Cancer Invest, 28, 554-9. https://doi.org/10.3109/07357900903286925
- Ban KA, Godellas CV (2014). Epidemiology of Breast Cancer. Surg Oncol Clin N Am, 3, 409-22.
- Buser K, Joncourt F, Altermatt HJ, et al (1997). Breast cancer: pretreatment drug resistance parameters (GSH-system, ATase, P-glycoprotein) in tumor tissue and their correlation with clinical and prognostic characteristics. Ann Oncol, 8, 335-41. https://doi.org/10.1023/A:1008202723066
- Cairns J, Wright C, Cattan AR, et al (1992). Immunohistochemical demonstration of glutathione S-transferases in primary human breast carcinomas. J Pathol, 166, 19-25. https://doi.org/10.1002/path.1711660105
- Curran JE, Weinstein SR, Griffiths LR (2000) Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility. Cancer Lett, 153, 113-120. https://doi.org/10.1016/S0304-3835(00)00361-X
- Das P, Singal R (2004). DNA methylation and cancer. J Clin Oncol, 22, 4632-4642. https://doi.org/10.1200/JCO.2004.07.151
- Di Cosimo S, Baselga J (2010). Management of breast cancer with targeted agents: importance of heterogeneity. Nat Rev Clin Oncol, 3, 139-47.
- Egan KM, Cai Q, Shu XO, et al (2004). Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai Breast Cancer Study and meta-analysis. Cancer Epidemiol Biomarkers Prev, 13, 197-204. https://doi.org/10.1158/1055-9965.EPI-03-0294
- Eunice C, Shui L, Kin F, Yok K (2005). Polymorphisms of the GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes in Chinese patients with non-small cell lung cancers: relationship with aberrant promoter methylation of the CDKN2A and RARB genes. Cancer Genet Cytogenet, 162, 10-20. https://doi.org/10.1016/j.cancergencyto.2005.03.008
- Ge J, Tian AX, Wang QS, et al (2013). The GSTP1 105Val allele increases breast cancer risk and aggressiveness but enhances response to cyclophosphamide chemotherapy in North China. PLoS One, 8, 67589. https://doi.org/10.1371/journal.pone.0067589
- Gilbert L, Elwood LJ, Merino M, et al (1993). A pilot study of piclass glutathione S-transferase expression in breast cancer: correlation with estrogen receptor expression and prognosis in node-negative breast cancer. J Clin Oncol, 11, 49-58.
- Gudmundsdottir K, Tryggvadottir L, Eyfjord JE (2001). GSTM1, GSTT1, and GST-PI genotypes in relation to breast cancer risk and frequency of mutations in the p53 gene. Cancer Epidemiol Biomarkers Prev, 10, 1169-1173.
- Haas S, Pierl C, Harth V, et al (2006). Expression of xenobiotic and steroid hormone metabolizing enzymes in human breast carcinomas. Int J Cancer, 119, 1785-91. https://doi.org/10.1002/ijc.21915
- Hamilton DS, Zhang X, Ding Z, et al (2003). Mechanism of the glutathione transferase-catalyzed conversion of antitumor 2-crotonyloxymethyl-2-cycloalkenones to GSH adducts. J Am Chem Soc, 49, 15049-58.
- Hammond ME, Hayes DF, Dowsett M, et al (2010). American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol, 28, 2784-95. https://doi.org/10.1200/JCO.2009.25.6529
- Helzlsouer J, Selmin O, Huang Y, et al (1998). Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J Natl Cancer Inst, 90, 513-8.
- Hisako I, Chikako K, Sachiko S, et al (2001). Glutathione S-transferase polymorphisms and risk of colorectal adenomas. Cancer Lett, 163, 201-6. https://doi.org/10.1016/S0304-3835(00)00692-3
- Horita K, Yamaguchi A, Hirose K, et al (2001). Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer. Eur J Histochem, 1,73-84.
- Huang J, Tan PH, Thiyagarajan J, Bay BH (2003). Prognostic significance of glutathione S-transferase-pi in invasive breast cancer. Mod Pathol, 16, 558-65. https://doi.org/10.1097/01.MP.0000071842.83169.5A
- Joanne E. Currana, R. Weinsteinb, Lyn R (2000). Griffithsa, Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility, Cancer Lett, 153, 113-120. https://doi.org/10.1016/S0304-3835(00)00361-X
- Kadouri L, Kote-Jarai Z, Hubert A, et al (2008) Glutathione- S-transferase M1, T1 and P1 polymorphisms, and breast cancer risk, in BRCA1/2 mutation carriers. Br J Cancer, 98, 2006-10. https://doi.org/10.1038/sj.bjc.6604394
- Kaptain S, Tan LK, Chen B (2001). Her-2/neu and breast cancer. Diagn Mol Pathol, 3, 139-52.
- Khabaz MN (2014). Polymorphism of the Glutathione S-Transferase P1 Gene (GST-pi) in breast carcinoma. Pol J Pathol, 65, 141-6.
- Kim SU, Lee KM, Park SK, et al (2004). Genetic polymorphism of glutathione S-transferase P1 and breast cancer risk. J Biochem Mol Biol, 37, 582-5. https://doi.org/10.5483/BMBRep.2004.37.5.582
- Lee SA, Fowke JH, Lu W, et al (2008). Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk. Am J Clin Nutr, 87, 753-60.
- Millikan R, Pittman G, Tse CK, et al (2000). Glutathione S-transferases M1, T1, and P1 and breast cancer. Cancer Epidemiol Biomarkers Prev, 9, 567-73.
- Mitrunen K, Jourenkova N, Kataja V, et al (2001). Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. Cancer Epidemiol Biomarkers Prev, 10, 229-36.
- Mohammadzadeha S, Nasseri M, Rasaee J, et al (2003). Measurement of glutathione S-transferase and its class- in plasma and tissue biopsies obtained after laparoscopy and endoscopy from subjects with esophagus and gastric cancer. Clin Biochem, 36, 283-88. https://doi.org/10.1016/S0009-9120(03)00012-2
- Moureau-Zabotto L, Ricci S, Lefranc JP, et al (2006). Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients. Br J Cancer, 94, 473-80. https://doi.org/10.1038/sj.bjc.6602958
- Ng CH, Pathy NB, Taib NA, et al (2014). Do clinical features and survival of single hormone receptor positive breast cancers differ from double hormone receptor positive breast cancers? Asian Pac J Cancer Prev, 15, 7959-64. https://doi.org/10.7314/APJCP.2014.15.18.7959
- Nourazarian AR, Kangari P, Salmaninejad A (2014). Roles of oxidative stress in the development and progression of breast cancer. Asian Pac J Cancer Prev, 15, 4745-51. https://doi.org/10.7314/APJCP.2014.15.12.4745
- Osborne CK, Yochmowitz MG, Knight WA 3rd, McGuire WL (1980). The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer, 46, 2884-8. https://doi.org/10.1002/1097-0142(19801215)46:12+<2884::AID-CNCR2820461429>3.0.CO;2-U
- Pongtheerat T, Pakdeethai S, Purisa W, et al (2011). Promoter methylation and genetic polymorphism of glutathione S-transferase P1 gene (GSTP1) in Thai breast-cancer patients. Asian Pac J Cancer Prev, 12, 2731-4.
- Pongtheerat T, Treetrisool M, Purisa W (2009). Glutathione s-transferase polymorphisms in breast cancers of Thai patients. Asian Pac J Cancer Prev, 10, 127-32.
- Prat A, Perou CM (2011). Deconstructing the molecular portraits of breast cancer. Mol Oncol, 1, 5-23.
- Ramalhinho AC, Fonseca-Moutinho JA, Breitenfeld L (2011). Glutathione S-transferase M1, T1, and P1 genotypes and breast cancer risk: a study in a Portuguese population. Mol Cell Biochem, 355, 265-271. https://doi.org/10.1007/s11010-011-0863-9
- Ramalhinho AC, Fonseca-Moutinho JA, Breitenfeld Granadeiro LA (2012). Positive association of polymorphisms in estrogen biosynthesis gene, cyp19a1, and metabolism, GST, in breast cancer susceptibility. DNA Cell Biol, 31, 1100-06. https://doi.org/10.1089/dna.2011.1538
- Rodriguez M, Mejia F, Lecourtois M, Dominguez V, Castillo J (2014). Influence of GSTT1, GSTM1 and GSTP1 polymorphisms on the development of breast cancer. J Cancer Therapy, 5, 552-9 https://doi.org/10.4236/jct.2014.56063
- Romero A, Martin M, Oliva B, et al (2012). Glutathione S-transferase P1 c.313A > G polymorphism could be useful in the prediction of doxorubicin response in breast cancer patients. Ann Oncol, 23, 1750-6. https://doi.org/10.1093/annonc/mdr483
- Ross JS, Slodkowska EA, SymmansWF, et al (2009). The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist, 14, 320-68. https://doi.org/10.1634/theoncologist.2008-0230
- Samson M, Swaminathan R, Rama R, et al (2007). Role of GSTM1 (Null/Present), GSTP1 (Ile105Val) and P53 (Arg72Pro) genetic polymorphisms and the risk of breast cancer: a case control study from South India. Asian Pac J Cancer Prev, 8, 253-7.
- Saxena A, Dhillon VS, Raish M, et al (2009). Detection and relevance of germline genetic polymorphisms in glutathione S-transferases (GSTs) in breast cancer patients from northern Indian population. Breast Cancer Res Treat, 115, 537-43. https://doi.org/10.1007/s10549-008-0098-y
- Saxena A, Dhillon VS, Shahid M, et al (2013). GSTP1 methylation and polymorphism increase the risk of breast cancer and the effects of diet and lifestyle in breast cancer patients. Exp Ther Med, 4, 1097-1103.
- Silvestrini R, Veneroni S, Benini E, et al (1997). Expression of p53, glutathione S-transferase-pi, and Bcl-2 proteins and benefit from adjuvant radiotherapy in breast cancer. J Nat Cancer Inst, 89, 639-45. https://doi.org/10.1093/jnci/89.9.639
- Sofi GN, Sofi JN, Nadeem R, et al (2012). Estrogen receptor and progesterone receptor status in breast cancer in relation to age, histological grade, size of lesion and lymph node involvement. Asian Pac J Cancer Prev, 13, 5047-52. https://doi.org/10.7314/APJCP.2012.13.10.5047
- Sreenath AS, Kumar KR, Reddy GV, et al (2005). Evidence for the association of synaptotagmin with glutathione S-transferases: implications for a novel function in human breast cancer. Clin Biochem, 38, 436-43. https://doi.org/10.1016/j.clinbiochem.2005.01.009
- Tamimi RM, Colditz GA, Hazra A, et al (2012). Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer. Breast Cancer Res Treat, 1, 159-67.
- Tavassoli FA, Devilee P (2003). Pathology and genetics. in tumors of the breast and female genital organs, WHO Classification of Tumors Series. IARC Press, Lyon, France, pp. 32-34.
- Unlu A, Ates NA, Tamer L, et al (2008). Relation of glutathione S-transferase T1, M1 and P1 genotypes and breast cancer risk. Cell Biochem Funct, 26, 643-647. https://doi.org/10.1002/cbf.1490
- Vogl FD, Taioli E, Maugard C, et al (2004). Glutathione S-transferases M1, T1, and P1 and breast cancer: a pooled analysis. Cancer Epidemiol Biomarkers Prev, 13, 1473-9.
- Welfare M, Adeokun M, Margaret F, Bassendine, Ann D (1999). Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer. Cancer Epidemiol Biomarkers Prev, 8, 289-92.
- Wu MS, Chen CJ, Lin MT, et al (2002). Genetic polymorphisms of cytochrome P4502E1, glutathione S-transferase M1 and T1, and susceptibility to gastric carcinoma in Taiwan. Int J Colorectal Dis, 17, 338-43. https://doi.org/10.1007/s00384-001-0383-2
- Yang G, Shu XO, Ruan ZX, et al (2005). Genetic polymorphisms in glutathione-S-transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma. Cancer, 103, 52-8. https://doi.org/10.1002/cncr.20729
- Yang X, Yan L, Davidson E (2001). DNA methylation in breast cancer. Endocr Relat Cancer, 8, 115-127. https://doi.org/10.1677/erc.0.0080115
- Zhang B, Beeghly-Fadiel A, Lu W, et al (2011). Evaluation of functional genetic variants for breast cancer risk: results from the Shanghai breast cancer study. Am J Epidemiol, 173, 1159-70. https://doi.org/10.1093/aje/kwr004
- Evaluation of Common Risk Factors for Breast Carcinoma in Females: a Hospital Based Study in Karachi, Pakistan vol.16, pp.15, 2015, https://doi.org/10.7314/APJCP.2015.16.15.6347