This study aimed to demonstrate the relationship between three types of polymorphisms in the promoter region of the ESR2 gene and susceptibility to ovarian cancer. The researchers used PCR to identify polymorphisms (SNPs) in 184 ovarian cancer patient samples and 184 control samples. They found that the different genotypes of the SNPs analyzed did not show a significant statistical difference between patients and controls. However, one SNP was found to be weakly associated with later FIGO stages of ovarian cancer. The study concludes that while the polymorphisms may be related to disease progression, they do not appear to influence susceptibility to ovarian cancer.

1. Polymorphisms in the promoter region of
ESR2 gene and susceptibility to
ovarian cancer
Susanne Schüler, Claus Lattricha, Maciej Skrzypczak, Tanja Fehmc,
Olaf Ortmanna, Oliver Treeck.
By
Tatiana Reyes
Andrea Urrego Vásquez

2. INTRODUCTION
CANCER
• Group of diseases characterized by the uncontrolled growth of abnormal cells in
the body and followed by metastasis.
• Can be regarded as a genetic disease that occurs in most of the tissues, and in all
types of somatic cells.
• It is associated with the reduction of apoptosis
– Oncogene.
– Tumor suppressor (oncosupresor)

3. INTRODUCTION
Progenitor
cell of
cancer
(mutate)
Neoplastic
clone cells
(new
mutation)
Metastasis

4. INTRODUCTION
OVARIAN CA
• Is the sixth most common cancer among women
• The etiology and pathogenesis of this tumor entity are not completely
understood (60-80%)
• It has major incidence after menopause
• Ovarian epithelia is capable of simulating all normal tissues from Muller´s
ducts, it attributes it metaplasic´s skill.

5. 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 estrogen
response elements (EREs), to DNA sequences, to facilitate recruitment of
the RNA polymerase II.
INTRODUCTION

7. INTRODUCTION
PROMOTERS
• Region of DNA, determines the place where the RNA
polymerase 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 and
proteins

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

9. • 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

10. OBJECTIVE
Demonstrate the relationship
between 3 types of
polymorphisms in the promoter
region of ESR2 gene with the
susceptibility to ovarian cancer

11. 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).

12. PCR
• Reacción en cadena de la polimerasa
• Consiste en la amplificación enzimática in vitro de moléculas
de DNA o RNA
• Permite la obtención de millones de copias del fragmento a
partir de una muy bajo concentración de este.
MATERIALES Y MÉTODOS

13. 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

14. Fig. 1.
• Tres SNPs en la región promotora
del gen ESR2
• ESR2 CA ovario
• Cromosoma 14
RESULTADOS

15. Fig. 2.
• SNPs EGA
• Homocigótico vs
heterocigótico
• Amplificación del resultado
RESULTADOS

16. • SNPs = Heterocigótico
• Distintos resultados
demostraron que no existe
relación entre estos SNPs y
el riesgo de desarrollar la
enfermedad
RESULTADOS

17. 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

18. 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

19. • The PCR technique was used in this study with the
objective to amplify a special region from ESR2 gene to
identify some polymorphisms probability related with
susceptibility of ovarian cancer
• The different genotypes to SNPs does not have a
significant neither statistically difference between ovarian
cancer patients and control group
CONCLUSIONS

20. • The three SNPs analyzed in this study had a great
relationship with FIGO stage III + IV. Principally SNP
rs3020449 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 not
have relation with the etiology of ovarian cancer but might
be in relationship with later stages of this disease and its
progression
CONCLUSIONS

21. Tatiana Reyes

22. Andrea Urrego

23. BIBLIOGRAPHY
• Martinéz Lina M. Vargas Natalia, Pamplona Ana P. Quevedo Esteban. Biología
molecular. 7ma ed. Medellín,Colombia: Editorial Universidad Pontificia Bolivariana,
2012.
• Karp, Gerald. Biología celular y molecular, conceptos y experimentos. 5ta ed. México:
McGraw Hill. 2008
• Lodish, H. Biología celular y molecular. 5ta edición. Buenos Aires: Medica
Panamericana.2004
• "Cáncer De Ovario Factores Pronóstico Y Expectativas De Futuro." Google Books. N.p.,
n.d. Web. 10 Aug. 2014. Pag 21-23.
• "Arici, A., Clínicas Obstétricas Y Ginecológicas De Norteamérica 2006, No 1: Miomas
©2007." Google Books. N.p., n.d. Web. 10 Aug. 2014. Pag 23.
• "ESR2 (Estrogen Receptor 2 (ER Beta))." ESR2 (Estrogen Receptor 2 (ER Beta)). N.p., n.d.
Web. 10 Aug. 2014.
• "Promotor - Medicina Molecular." Promotor - Medicina Molecular. N.p., n.d. Web. 10
Aug. 2014.
• Esteller Manel. "DNA Methylation, Epigenetics and Metastasis." Google Books. Springer,
n.d. Web. 10 Aug. 2014. Pag 93.