Association of estrogen receptor α and β3-adrenergic receptor polymorphisms with endometrial cancer

Iwamoto, Ichiro; Fujino, Toshinori; Douchi, Tsutomu; Nagata, Yukihiro

doi:10.1016/s0029-7844(03)00578-7

Cited by 21 publications

(14 citation statements)

References 21 publications

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“…A number of studies have previously been performed to investigate the hypothesis that variation at the ESR1 locus may be associated with predisposition to endometrial cancer (Ashton, et al 2009, 2010; Einarsdottir, et al 2009; Einarsdottir, et al 2008; Iwamoto, et al 2003; Li, et al 2011; Sasaki, et al 2002; Sliwinski, et al 2010; Wedren, et al 2008; Weiderpass, et al 2000), but results from these relatively underpowered studies (maximum sample size 713 cases and 1567 controls) have been conflicting. However, comprehensive candidate gene and genome-wide association studies of breast cancer, which shares many risk factors with endometrial cancer, have identified cancer-associated risk variants at the ESR1 locus (Dunning, et al 2009; Hein, et al 2012; Turnbull, et al 2010; Zheng, et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer

O’Mara¹,

Glubb²,

Painter³

et al. 2015

Endocrine-Related Cancer

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Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3,633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6,607 EC cases and 37,925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P = 1.86 × 10−5), which was stronger for cancers of endometrioid subtype (P = 3.76 × 10−6). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.

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Section: Introductionmentioning

confidence: 99%

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer

O’Mara¹,

Glubb²,

Painter³

et al. 2015

Endocrine-Related Cancer

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“…Hypothetically, β-ADRs may play a more specialized role in development of uterine cancer. In contrast to the other gynecologic cancers where the β 2 -ADR is important, the limited data on beta adrenergic receptors is focused on the β 3- ADR since it is one of the genes important in obesity and insulin resistance [86]. However, this area will require further investigation to understand the full scope of such effects.…”

Section: Introductionmentioning

confidence: 99%

Importance of adrenergic pathways in women's cancers

Thaker

Sood²,

Ramondetta³

2013

CBM

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“…Genetic variation in the ESR genes can potentially result in ESRs with altered binding kinetics that adversely affect cellular metabolism. There is evidence to suggest that two ESR1 polymorphisms (rs2234693 (PvuII) and rs9340799 (XbaI)) and an ESR2 polymorphism (rs944050) affect receptor function because of differential splicing of the mRNA transcript 8–11 . RNA stability of the ESR2 transcript is also considered to be affected by two other ESR2 polymorphisms (rs1255998 and rs4986938) located in the 3′ untranslated region of the gene 12,13 .…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor polymorphisms and the risk of endometrial cancer

Ashton

Proietto

Otton

et al. 2009

BJOG

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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.

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Association of estrogen receptor α and β3-adrenergic receptor polymorphisms with endometrial cancer

Abstract: Estrogen receptor alpha polymorphisms, but not beta3-adrenergic receptor gene, may be associated with a risk of endometrial cancer.

Cited by 21 publications

References 21 publications

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer

Importance of adrenergic pathways in women's cancers

Estrogen receptor polymorphisms and the risk of endometrial cancer

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