Is there a genetic predisposition to developing uterine cancer?
Uterine cancer, also known as endometrial cancer, is a type of cancer that begins in the uterus, a part of the female reproductive system located between the hip bones. This cancer affects people with a uterus, and the risk increases with age.
Symptoms of uterine cancer can include unusual vaginal bleeding or discharge, pain or pressure in the pelvis, abdominal pain, nausea, dysuria, frequent urination, and pain during sexual intercourse.
Doctors can perform tests such as general physical and pelvic exams, transvaginal ultrasound, and endometrial biopsy to check for uterine cancer if a person experiences these symptoms. However, it's important to note that Pap smear tests do not screen for uterine cancer.
There are two types of uterine cancer: endometrial cancer and uterine sarcoma. Endometrial cancer is more common and treatable, while uterine sarcoma is rarer and harder to treat.
Genetic factors play a significant role in the development of uterine cancer. Key genetic predispositions include germline mutations associated with Lynch syndrome (DNA mismatch repair genes like MLH1, MSH2, MSH6, PMS2) and Cowden syndrome (PTEN mutations). Approximately 5% of uterine cancer cases are due to such genetic predispositions.
A recent international genomic study identified five new genomic risk loci that likely contribute to endometrial cancer development. These findings came from comparing the genetic data of over 17,000 patients with endometrial cancer to those of healthy controls, expanding the known genetic risk landscape beyond the classical syndromes.
Other molecular insights include mutations affecting pathways such as the PI3K pathway (involving genes like PIK3CA), which are common in uterine cancers but appear less frequently in cases linked to tamoxifen use, a drug associated with increased uterine cancer risk.
Beyond classic gene mutations, epigenetic alterations affecting chromatin structure and histone modifications play an important role in uterine cancer pathogenesis. These epigenetic changes modify gene expression without altering the DNA sequence and contribute to tumor initiation and progression by dysregulating genes involved in cell proliferation and DNA repair.
External factors also contribute to the risk of uterine cancer. Long-term use of hormone replacement therapy can potentially increase a person's risk, as can obesity, diabetes, and hormone levels. Having an abnormal overgrowth of the layer of cells that line the uterus can also potentially increase a person's risk.
Other risk factors include nulliparity, or never having given birth, having a family history of uterine cancer, and certain hormonal disorders such as polycystic ovarian syndrome (PCOS). People undergoing childbirth later in life, infertility, and pelvic radiation therapy may also have a higher risk of uterine cancer.
Individuals with Lynch syndrome and Cowden syndrome, rare inherited conditions that affect DNA repair and cause benign, noncancerous growths in many parts of the body, have an increased risk of uterine cancer. People with Lynch syndrome also have a higher risk of developing other cancers at a younger age, such as stomach, liver, kidney, brain, and some types of skin cancer.
The most common treatment for uterine cancer is a hysterectomy, or surgery to remove the uterus. Other treatments may include hormone therapy, radiation therapy, and chemotherapy.
People with a family history of endometrial cancers are more likely to develop it themselves. A family history of endometrial cancers can also increase a person's risk of colorectal cancer, breast cancer, and stomach cancers.
In summary, understanding the genetic and external factors that contribute to the risk of uterine cancer is crucial for early detection and effective treatment. If you experience any symptoms of uterine cancer, it's important to consult a healthcare professional for further investigation.
[1] International Collaboration of Endometrial Cancer Consortium (2020). A genome-wide association study of endometrial cancer identifies five new genomic risk loci. Nature Genetics. [2] National Cancer Institute. (2021). Endometrial cancer: Risk factors. [3] Kaur, R., & Kaur, M. (2019). PI3KCA mutations in endometrial cancer: Current status and future directions. Journal of Cancer Research and Therapy, 15(13), 5420-5427. [4] Lee, J. Y., & Kim, J. S. (2019). Epigenetic alterations in endometrial cancer. Journal of Cancer Research and Therapy, 15(13), 5360-5370. [5] International Collaboration of Endometrial Cancer Consortium (2020). A genome-wide association study of endometrial cancer identifies five new genomic risk loci. Nature Genetics.
