Endometrial Cancer Risks: Genetic Regulation of Blood Estrone Levels in Postmenopausal Women

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Introduction

Endometrial Cancer Risks: The study published in eBioMedicine explores the genetic regulation of blood estrone levels in postmenopausal women and its connection to endometrial cancer risk. Estrone, a key estrogen in postmenopausal women, is produced outside the ovaries, mainly in fat tissues, and is associated with Type 1 estrogen-sensitive endometrial cancer, which predominantly affects menopausal women. The research aims to identify genetic factors influencing estrone levels and their implications for endometrial cancer risk.

Endometrial Cancer Risks

Endometrial Cancer Risks: Estrogens and Endometrial Cancer

After menopause, ovaries cease estrogen production, leading to low estradiol levels. In Type 1 endometrial cancer, estrone, derived from non-ovarian tissues like fat, plays a crucial role. Obesity, linked to increased estrone production, is a known risk factor for this type of cancer. Genetic factors, including variants in genes like CYP19A1, which influences estradiol production, also contribute to endometrial cancer risk in postmenopausal women.

Study Overview

The genome-wide association study (GWAS) involved precise measurement of blood hormone levels using liquid chromatography-tandem mass spectrometry (LCMS) in a large cohort of postmenopausal women. Researchers examined the association between hormone-related genetic variants and endometrial cancer risk in over 4,900 women of European descent.

Related: World Ovarian Cancer Day 2023: Understanding the Disease and Raising Awareness

Study Findings

While no significant associations were found for testosterone or DHEA levels, four independent genetic variants were identified to influence estrone concentrations. These variants, including rs34670419, rs56400819, rs2846729, and rs2414098, showed different prevalence rates within the cohort. Carriers of certain variants exhibited lower estrone levels and reduced endometrial cancer risk, notably rs2414098 carriers.

Implications and Conclusions

Unlike previous studies focusing on estradiol, this research emphasizes the significance of measuring estrone levels in assessing endometrial cancer risk in postmenopausal women. By identifying genetic variants associated with estrone levels, particularly rs2414098, the study provides insights into potential preventive strategies. Key strengths include a sizable cohort, accurate hormone measurement using LCMS, and confirmation of postmenopausal status, enhancing the study’s credibility and relevance.

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