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Estrogen receptor polymorphisms and the risk of endometrial cancer.
BJOG. 2009 Jul; 116(8):1053-61.BJOG

Abstract

OBJECTIVE

There is evidence that estrogens and some of their metabolites are involved in endometrial cancer pathogenesis. As estrogens mediate their effects via the estrogen receptors, ESR1 and ESR2, the objective of this investigation was to determine whether six single nucleotide polymorphisms (SNPs) in these two genes were over-represented in a population of endometrial cancer patients compared with a healthy matched control population, thereby associating differences in these genes with endometrial cancer.

DESIGN

The study is a case-control investigation large enough to detect a two-fold increased risk, assuming a dominant genetic model, with P = 0.05 and 80% power.

SETTING

The study and control populations were all from the Hunter-New England region of New South Wales, Australia collected between the years 1992 and 2005.

POPULATION

The study consisted of 191 endometrial cancer patients and 291 healthy controls matched for gender and age.

METHODS

Two SNPs in ESR1 and four SNPs in ESR2 were genotyped using PCR-based restriction fragment length polymorphism analysis and real-time PCR. Odds ratios were calculated using unconditional logistic regression and SIMHAP was used for haplotype analysis, adjusting for potential endometrial cancer risk factors. Kaplan-Meier survival analysis, Cox regression and t tests were used to examine the patient's age of diagnosis of endometrial cancer and genotype.

MAIN OUTCOME MEASURES

Over-representation of ESR1 and ESR2 polymorphisms in the endometrial cancer population compared with the control population indicates an involvement in the development and/or progression of disease.

RESULTS

Two ESR1 (rs2234693 and rs9340799) and two ESR2 (rs1255998 and rs944050) polymorphisms were associated with an increased risk of endometrial cancer. Following adjustment for risk factors, the association with the ESR1 and ESR2 polymorphisms (rs2234693, rs1255998 and rs944050) remained highly significant. Haplotype analysis revealed that carriers of the ESR1 haplotype (variant alleles; rs2234693 and rs9340799) and the ESR2 haplotype (variant allele; rs1255998 and wild-type alleles; rs944050, rs4986938 and rs1256049) were at an increased risk (OR 1.862, P = 0.013 and OR 1.918, P = 0.046 respectively). This risk was even greater in women carrying both risk haplotypes (OR 5.041, P = 0.007).

CONCLUSIONS

Our data suggest that the ESR1 (rs2234693 and rs9340799) and the ESR2 (rs1255998 and rs944050) polymorphisms may be associated with an increased risk of developing endometrial cancer.

Authors+Show Affiliations

Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle; and the Hunter Medical Research Institute, Newcastle, NSW, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19438492

Citation

Ashton, K A., et al. "Estrogen Receptor Polymorphisms and the Risk of Endometrial Cancer." BJOG : an International Journal of Obstetrics and Gynaecology, vol. 116, no. 8, 2009, pp. 1053-61.
Ashton KA, Proietto A, Otton G, et al. Estrogen receptor polymorphisms and the risk of endometrial cancer. BJOG. 2009;116(8):1053-61.
Ashton, K. A., Proietto, A., Otton, G., Symonds, I., McEvoy, M., Attia, J., Gilbert, M., Hamann, U., & Scott, R. J. (2009). Estrogen receptor polymorphisms and the risk of endometrial cancer. BJOG : an International Journal of Obstetrics and Gynaecology, 116(8), 1053-61. https://doi.org/10.1111/j.1471-0528.2009.02185.x
Ashton KA, et al. Estrogen Receptor Polymorphisms and the Risk of Endometrial Cancer. BJOG. 2009;116(8):1053-61. PubMed PMID: 19438492.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen receptor polymorphisms and the risk of endometrial cancer. AU - Ashton,K A, AU - Proietto,A, AU - Otton,G, AU - Symonds,I, AU - McEvoy,M, AU - Attia,J, AU - Gilbert,M, AU - Hamann,U, AU - Scott,R J, Y1 - 2009/05/11/ PY - 2009/5/15/entrez PY - 2009/5/15/pubmed PY - 2009/8/12/medline SP - 1053 EP - 61 JF - BJOG : an international journal of obstetrics and gynaecology JO - BJOG VL - 116 IS - 8 N2 - OBJECTIVE: There is evidence that estrogens and some of their metabolites are involved in endometrial cancer pathogenesis. As estrogens mediate their effects via the estrogen receptors, ESR1 and ESR2, the objective of this investigation was to determine whether six single nucleotide polymorphisms (SNPs) in these two genes were over-represented in a population of endometrial cancer patients compared with a healthy matched control population, thereby associating differences in these genes with endometrial cancer. DESIGN: The study is a case-control investigation large enough to detect a two-fold increased risk, assuming a dominant genetic model, with P = 0.05 and 80% power. SETTING: The study and control populations were all from the Hunter-New England region of New South Wales, Australia collected between the years 1992 and 2005. POPULATION: The study consisted of 191 endometrial cancer patients and 291 healthy controls matched for gender and age. METHODS: Two SNPs in ESR1 and four SNPs in ESR2 were genotyped using PCR-based restriction fragment length polymorphism analysis and real-time PCR. Odds ratios were calculated using unconditional logistic regression and SIMHAP was used for haplotype analysis, adjusting for potential endometrial cancer risk factors. Kaplan-Meier survival analysis, Cox regression and t tests were used to examine the patient's age of diagnosis of endometrial cancer and genotype. MAIN OUTCOME MEASURES: Over-representation of ESR1 and ESR2 polymorphisms in the endometrial cancer population compared with the control population indicates an involvement in the development and/or progression of disease. RESULTS: Two ESR1 (rs2234693 and rs9340799) and two ESR2 (rs1255998 and rs944050) polymorphisms were associated with an increased risk of endometrial cancer. Following adjustment for risk factors, the association with the ESR1 and ESR2 polymorphisms (rs2234693, rs1255998 and rs944050) remained highly significant. Haplotype analysis revealed that carriers of the ESR1 haplotype (variant alleles; rs2234693 and rs9340799) and the ESR2 haplotype (variant allele; rs1255998 and wild-type alleles; rs944050, rs4986938 and rs1256049) were at an increased risk (OR 1.862, P = 0.013 and OR 1.918, P = 0.046 respectively). This risk was even greater in women carrying both risk haplotypes (OR 5.041, P = 0.007). CONCLUSIONS: Our data suggest that the ESR1 (rs2234693 and rs9340799) and the ESR2 (rs1255998 and rs944050) polymorphisms may be associated with an increased risk of developing endometrial cancer. SN - 1471-0528 UR - https://www.unboundmedicine.com/medline/citation/19438492/Estrogen_receptor_polymorphisms_and_the_risk_of_endometrial_cancer_ L2 - https://doi.org/10.1111/j.1471-0528.2009.02185.x DB - PRIME DP - Unbound Medicine ER -