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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...

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Autores principales: Savukaitytė, Aistė, Ugenskienė, Rasa, Jankauskaitė, Roberta, Čereškevičius, Darius, Šepetauskienė, Eglė, Juozaitytė, Elona
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
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.
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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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