Endometrial carcinoma arises from a complex interplay of genetic, hormonal, and environmental factors. The etiology can be summarized as follows:
## Hormonal Factors
Estrogen plays a crucial role in the development of endometrial cancer, particularly in low-grade endometrioid carcinomas. Prolonged exposure to unopposed estrogen stimulation is a key factor[1][2]. This can occur due to:
- Obesity, which increases endogenous estrogen production
- Early menarche or late menopause
- Anovulation
- Hormone replacement therapy with estrogen alone
- Estrogen-producing tumors
Progesterone typically counteracts estrogen's effects, so an imbalance between these hormones can increase cancer risk.
## Genetic Factors
Several genetic mutations are associated with endometrial cancer:
- PTEN mutations are common in low-grade endometrioid carcinomas[2]
- TP53 mutations are frequently found in aggressive serous and clear cell carcinomas[2]
- Lynch syndrome, caused by mutations in mismatch repair genes, significantly increases endometrial cancer risk[5]
- Other genes implicated include KRAS2, ARID1A, and those involved in microsatellite instability[2]
## Environmental and Lifestyle Factors
- Obesity is a major risk factor, likely due to its effects on hormone levels and insulin resistance[3]
- Diabetes and polycystic ovary syndrome (PCOS) increase risk, possibly through hormonal mechanisms[3]
- Tamoxifen use for breast cancer treatment can increase endometrial cancer risk[3]
## Precursor Lesions
Endometrial intraepithelial neoplasia (EIN), formerly known as atypical endometrial hyperplasia, is a precursor lesion that can progress to endometrioid carcinoma[2].
Citations:
[1] https://www.cancer.org/cancer/types/endometrial-cancer/causes-risks-prevention/what-causes.html
[2] https://www.ncbi.nlm.nih.gov/books/NBK525981/
[3] https://www.hopkinsmedicine.org/health/conditions-and-diseases/endometrial-cancer
[4] https://emedicine.medscape.com/article/254083-overview
[5] https://www.cancer.org/cancer/types/endometrial-cancer/causes-risks-prevention/risk-factors.html