Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer
書誌事項
- 公開日
- 2015-10
- DOI
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- 10.1530/erc-15-0319
- 公開者
- Bioscientifica
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説明
<jats:p>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<jats:italic>ESR1</jats:italic>. Consequently, several studies have investigated whether variation at the<jats:italic>ESR1</jats:italic>locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the<jats:italic>ESR1</jats:italic>gene (lead SNP rs79575945,<jats:italic>P</jats:italic>=1.86×10<jats:sup>−5</jats:sup>), which was stronger for cancers of endometrioid subtype (<jats:italic>P</jats:italic>=3.76×10<jats:sup>−6</jats:sup>). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting<jats:italic>ESR1</jats:italic>, and eQTL analysis found that rs79575945 was associated with expression of<jats:italic>SYNE1</jats:italic>, a neighbouring gene. In summary, we have identified a single EC risk signal located at<jats:italic>ESR1</jats:italic>, 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.</jats:p>
収録刊行物
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- Endocrine-Related Cancer
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Endocrine-Related Cancer 22 (5), 851-861, 2015-10
Bioscientifica
