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Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients
BACKGROUND: Breast cancer is the most frequent oncological disease among women. Estrogens are known to play an important role in breast cancer development. Recognition of the relationship between polymorphisms within estrogen metabolizing genes and conventional prognostic factors of breast cancer mi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410685/ https://www.ncbi.nlm.nih.gov/pubmed/25648141 http://dx.doi.org/10.1186/s12881-015-0147-4 |
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author | Savukaitytė, Aistė Ugenskienė, Rasa Jankauskaitė, Roberta Čereškevičius, Darius Šepetauskienė, Eglė Juozaitytė, Elona |
author_facet | Savukaitytė, Aistė Ugenskienė, Rasa Jankauskaitė, Roberta Čereškevičius, Darius Šepetauskienė, Eglė Juozaitytė, Elona |
author_sort | Savukaitytė, Aistė |
collection | PubMed |
description | BACKGROUND: Breast cancer is the most frequent oncological disease among women. Estrogens are known to play an important role in breast cancer development. Recognition of the relationship between polymorphisms within estrogen metabolizing genes and conventional prognostic factors of breast cancer might improve our knowledge on individualized breast cancer prognosis. Therefore, we aimed to investigate possible associations between germline genetic polymorphisms within GSTM1, GSTT1, GSTP1, SULT1A1 and UGT1A1 genes and breast cancer clinicopathological characteristics together with disease progression. METHODS: Our study involved 80 young (younger than 50 years of age) breast cancer patients. PCR-based Restriction Fragment Length Polymorphism (RFLP) assay was used to determine GSTP1 and SULT1A1 genotypes. GSTM1 and GSTT1 null genotypes were detected by multiplex PCR. UGT1A1 polymorphism was investigated with microsatellite analysis. Relationships between genotypes and breast cancer clinicopathological features along with disease progression were estimated by Pearson‘s Chi-square test. Logistic regression analyses were performed to estimate the odds ratios associating different genotypes with clinicopathological characteristics and disease progression. RESULTS: The study showed individuals with GSTT1 null genotype to have approximately 3.5 times higher risk for breast cancer progression than those with wild type genotype (OR = 3.472, 95% CI 1.043-11.559, P = 0.043). Moreover, SULT1A1 G638A AA genotype significantly increased the chances of HER2 molecular subtype breast cancer when compared to GG genotype (OR = 19.971, 95% CI 1.716-232.480, P = 0.017). Heterozygotes for GSTP1 A313G genotype were more likely to have positive lymph nodes in comparison to AA genotype carriers (OR = 2.803, 95% CI 1.049-7.487, P = 0.040). No significant correlation was determined for UGT1A1 A(TA)nTAA and GSTM1 +/- polymorphism alone or combined GTTT1 null and GSTM1 null genotype. CONCLUSIONS: Conclusively, our findings suggest that GSTT1 null genotype and SULT1A1 G638A AA genotype could be uselful genetic markers for breast cancer prognosis. Further analyses on larger sample size are required to highlight the effect of GSTP1 G allele on breast cancer prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0147-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4410685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44106852015-04-28 Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients Savukaitytė, Aistė Ugenskienė, Rasa Jankauskaitė, Roberta Čereškevičius, Darius Šepetauskienė, Eglė Juozaitytė, Elona BMC Med Genet Research Article BACKGROUND: Breast cancer is the most frequent oncological disease among women. Estrogens are known to play an important role in breast cancer development. Recognition of the relationship between polymorphisms within estrogen metabolizing genes and conventional prognostic factors of breast cancer might improve our knowledge on individualized breast cancer prognosis. Therefore, we aimed to investigate possible associations between germline genetic polymorphisms within GSTM1, GSTT1, GSTP1, SULT1A1 and UGT1A1 genes and breast cancer clinicopathological characteristics together with disease progression. METHODS: Our study involved 80 young (younger than 50 years of age) breast cancer patients. PCR-based Restriction Fragment Length Polymorphism (RFLP) assay was used to determine GSTP1 and SULT1A1 genotypes. GSTM1 and GSTT1 null genotypes were detected by multiplex PCR. UGT1A1 polymorphism was investigated with microsatellite analysis. Relationships between genotypes and breast cancer clinicopathological features along with disease progression were estimated by Pearson‘s Chi-square test. Logistic regression analyses were performed to estimate the odds ratios associating different genotypes with clinicopathological characteristics and disease progression. RESULTS: The study showed individuals with GSTT1 null genotype to have approximately 3.5 times higher risk for breast cancer progression than those with wild type genotype (OR = 3.472, 95% CI 1.043-11.559, P = 0.043). Moreover, SULT1A1 G638A AA genotype significantly increased the chances of HER2 molecular subtype breast cancer when compared to GG genotype (OR = 19.971, 95% CI 1.716-232.480, P = 0.017). Heterozygotes for GSTP1 A313G genotype were more likely to have positive lymph nodes in comparison to AA genotype carriers (OR = 2.803, 95% CI 1.049-7.487, P = 0.040). No significant correlation was determined for UGT1A1 A(TA)nTAA and GSTM1 +/- polymorphism alone or combined GTTT1 null and GSTM1 null genotype. CONCLUSIONS: Conclusively, our findings suggest that GSTT1 null genotype and SULT1A1 G638A AA genotype could be uselful genetic markers for breast cancer prognosis. Further analyses on larger sample size are required to highlight the effect of GSTP1 G allele on breast cancer prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0147-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-02-04 /pmc/articles/PMC4410685/ /pubmed/25648141 http://dx.doi.org/10.1186/s12881-015-0147-4 Text en © Savukaitytė et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Savukaitytė, Aistė Ugenskienė, Rasa Jankauskaitė, Roberta Čereškevičius, Darius Šepetauskienė, Eglė Juozaitytė, Elona Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients |
title | Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients |
title_full | Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients |
title_fullStr | Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients |
title_full_unstemmed | Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients |
title_short | Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients |
title_sort | investigation of prognostic value of polymorphisms within estrogen metabolizing genes in lithuanian breast cancer patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410685/ https://www.ncbi.nlm.nih.gov/pubmed/25648141 http://dx.doi.org/10.1186/s12881-015-0147-4 |
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