Polymorphisms in the promoter region of ESR2 gene and susceptibility toovarian cancer

Susanne Schüler, Claus Lattricha, Maciej Skrzypczak, Tanja Fehmc, Olaf Ortmanna, Oliver Treeck.

ByTatiana Reyes

Andrea Urrego Vásquez

INTRODUCTION

CANCER

• Group of diseases characterized by the uncontrolled growth of abnormal cells inthe body and followed by metastasis.

• Can be regarded as a genetic disease that occurs in most of the tissues, and in alltypes of somatic cells.

• It is associated with the reduction of apoptosis

– Oncogene.

– Tumor suppressor (oncosupresor)

INTRODUCTION

Progenitor cell of cancer

(mutate)

Neoplasticclone cells

(new mutation)

Metastasis

INTRODUCTION

OVARIAN CA

• Is the sixth most common cancer among women

• The etiology and pathogenesis of this tumor entity are not completelyunderstood (60-80%)

• It has major incidence after menopause

• Ovarian epithelia is capable of simulating all normal tissues from Muller´sducts, it attributes it metaplasic´s skill.

GENE ESR2

• 8 encoding exons

• Estrogen β2 receptor gene

• Located in 14q

• Formed by an alternative splicing of the mRNA

• Regulation of gene expression, involves the direct binding of estrogenresponse elements (EREs), to DNA sequences, to facilitate recruitment ofthe RNA polymerase II.

INTRODUCTION

INTRODUCTION

PROMOTERS

• Region of DNA, determines the place where the RNApolymerase start the transcription of a gene

• RNA polymerase recognize the TATA box (-10 sequence)located in the promoter region.

• -35 sequence

• This binding also requires transcription factors andproteins

POLYMORPHISMS

Sites of the genome that change frequently between different individuals in the populations of a species.

INTRODUCTION

• ESR2 has at least two different promoters encoding mRNA that differs in 5’ utr.

• 0N methylated, related in breast cancer cells and primary tumors.

• SNPs (Single nucleotide polymorphisms) is useful for the study and the construction of genetics' maps.

INTRODUCTION

OBJECTIVE

Demonstrate the relationshipbetween 3 types ofpolymorphisms in the promoterregion of ESR2 gene with thesusceptibility to ovarian cancer

MATERIALES Y MÉTODOS

PACIENTES

• 184 muestras de sangre de mujeres caucásicas con cáncer de ovario 60,7 años (media).– Información sobre el grado, estado histopatológico desde 2002- 2012

• 184 muestras de sangre de mujeres caucásicas sin cáncer 60,8 años (media).

PCR

• Reacción en cadena de la polimerasa

• Consiste en la amplificación enzimática in vitro de moléculasde DNA o RNA

• Permite la obtención de millones de copias del fragmento apartir de una muy bajo concentración de este.

MATERIALES Y MÉTODOS

PCR

• Desnaturalización del DNA

• Hibridación primers (DNA corto)

• Replicación DNA polimerasa

Se utilizó para establecer e identificar los polimorfismos (SNPs)

rs3020449/ rs2987983/ rs3020450

MATERIALES Y MÉTODOS

Fig. 1.

• Tres SNPs en la región promotoradel gen ESR2

• ESR2 CA ovario

• Cromosoma 14

RESULTADOS

Fig. 2.

• SNPs EGA

• Homocigótico vs heterocigótico

• Amplificación del resultado

RESULTADOS

• SNPs = Heterocigótico

• Distintos resultadosdemostraron que no existerelación entre estos SNPs yel riesgo de desarrollar laenfermedad

RESULTADOS

AUTHOR YES NOT

Thellenberg-

Karlsson et al.,

2006; Treeck et

al., 2009

“This report is the first one analyzing the

association of ESR2 promoter SNPs

rs2987983 and rs3020449 with ovarian

cancer risk. However, one of these SNPs,

rs2987983, recently was found to be

associated with susceptibility to breast and

prostate cancers”

Leigh Pearce et

al., 2008

“Our negative results on SNP rs3020450

are in line and four other randomly chosen

ESR2 SNPs in ovarian cancer patients,

reporting n o association to ovarian cancer

risk”

DISCUSSION

AUTHOR YES NOT

Lurie et al., 2011 “Ovarian Cancer Association Consortium

examined another ESR2 polymorphism,

rs1271572, and found it to be weakly

associated with susceptibility to ovarian

cancer”

Bardin et al.,

2004; Rutherford

et al., 2000

“Our finding of a weak association of this

polymorphism (SNP rs3020449) with FIGO

staging is in line with studies reporting loss

of ERβ particularly in metastatic ovarian

cancer and further reports about deletion of

the ESR2 region in ovarian cancer,

suggesting that the gene may play a role in

disease progression, but not necessarily

susceptibility to disease”

DISCUSSION

• The PCR technique was used in this study with theobjective to amplify a special region from ESR2 gene toidentify some polymorphisms probability related withsusceptibility of ovarian cancer

• The different genotypes to SNPs does not have asignificant neither statistically difference between ovariancancer patients and control group

CONCLUSIONS

• The three SNPs analyzed in this study had a greatrelationship with FIGO stage III + IV. Principally SNPrs3020449 give us a statistically significant result with p =0.027 and p = 0.018 for allele genotypes in ovarian cancer

• The polymorphisms it was studied in this article does nothave relation with the etiology of ovarian cancer but mightbe in relationship with later stages of this disease and itsprogression

CONCLUSIONS

Tatiana Reyes

Andrea Urrego

BIBLIOGRAPHY

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