Can Endometriosis Cause Cancer
Extract
can endometriosis cause cancer? Here is your answer n depth. Endometriosis affects 5-10% of reproductive-aged women and is a hormone-dependent, chronic inflammatory condition characterized by the growth of endometrial-like tissue outside the uterus. It can cause chronic pelvic pain and infertility. The underlying molecular mechanisms of this disease are poorly understood, and current treatment options mainly focus on suppressing lesion activity rather than eliminating it entirely. While endometriosis is usually considered benign, evidence suggests it may increase the risk of certain types of ovarian cancer. Cancer driver mutations have been found in endometriotic lesions, indicating a potential connection to cancer pathways. Recent advancements in single-cell and spatial genomics, as well as the development of organoid models, are shedding light on the molecular mechanisms of the disease.
Introduction- Can Endometriosis Cause Cancer
Endometriosis, a condition that threatens the quality of life for young women and depends on estrogen, affects approximately 10% of the population. It is characterized by the presence of extra-uterine endometrial glands.
Endometriosis impacts approximately 5–10% of reproductive-age women and significantly affects quality of life due to debilitating pelvic pain and infertility. How can endometriosis cause cancer. This condition occurs when endometrial tissue is found outside the uterus, commonly on the ovaries, fallopian tubes, and pelvic peritoneum, but can also be found in other areas such as the lungs, liver, pericardium, surgical scars, limbs, and even the central nervous system. Endometriotic tissue, like the lining of the uterus, responds to hormones. As a result, the ectopic tissue undergoes changes during the menstrual cycle, similar to the normal endometrium, leading to cyclical bleeding within the pelvis, chronic inflammation, and progressive scarring of the surrounding tissue.
Can Endometriosis Cause Cancer;Ovarian
Epithelial ovarian carcinoma (EOC) is one of the most lethal cancers among gynecologic malignancies worldwide, with over 238,700 newly diagnosed cases and 151,900 reported deaths per year. EOC originates from ovarian surface epithelial/ neighboring fallopian tube cells and is known as a “silent killer” because patients are often asymptomatic until reaching an advanced stage. This tumor is commonly found in postmenopausal women and is highly heterogeneous, with different molecular backgrounds.
Clear cell carcinoma (CCC) is a rare malignancy in Western countries, accounting for less than 5% of all ovarian carcinomas. CCC is pathologically diagnosed if typical clear or hobnail cells are growing in a papillary, solid, or tubulocystic pattern. Despite its rarity, this histological type is widespread.
Symptoms
Diagnosing endometriosis can be difficult because symptoms vary significantly among affected individuals. The most common symptoms of endometriosis include pelvic pain, especially excessive menstrual cramps (dysmenorrhea); pain during intercourse; abnormal or heavy menstrual flow; and infertility. Other symptoms may include painful urination, bowel movements during menstruation, and gastrointestinal problems. Some patients may not show any symptoms at all. Infertile patients, in particular, may not experience pain but only have their disease diagnosed during infertility testing. The reasons for the differences in symptoms are not fully understood but may be related to the location of the abnormal tissue, the depth of infiltration, and the tendency for lesions to form scars or invade neuronal structures.
How can diagnose Endometriosis Cause Cancer
Currently, there are no universally validated diagnostic tests or screening tools that are specific to endometriosis. Often, healthcare providers rely on a thorough evaluation of menstrual symptoms and chronic pelvic pain to suspect the condition. However, as not all patients experience pain, infertility may be the first sign of the disease. The only definitive way to diagnose endometriosis is through surgical diagnosis or laparoscopy, which results in a 7- to 11-year-long latency period from the onset of symptoms to definitive diagnosis and carries an increased risk of disease progression within that period. However, noninvasive imaging methods, such as transvaginal ultrasound and magnetic resonance imaging (MRI), have improved the ability to diagnose endometriosis in recent years, allowing for the staging and classification of most forms of endometriosis without the need for surgical intervention.
Treatment
At the time of diagnosis, limited data on the optimal treatment options and short- or long-term prognoses are available. Medical professionals generally aim to control symptoms due to the lack of a cure for endometriosis. Progesterone-based therapy is commonly used for treatment, but up to 40% of patients may develop progesterone resistance. In some cases, synthetic androgen therapy or gonadotropin-releasing hormone (GnRH) agonists are prescribed to alleviate pain by inducing a hypoestrogenic state. However, these options are not considered long-term solutions due to their side effects. For patients who do not respond to hormonal therapy, extensive surgical removal may be necessary, which could involve segmental bowel excision and extirpative resection of pelvic tissues. Recurrence of lesions is common over time, potentially leading to the need for additional surgeries. Endometriosis is a condition associated with significant individual and public health challenges.
Development of Diseased Tissue
According to anatomical and histological criteria, endometriosis can classify into three distinct subtypes:
- superficial peritoneal endometriosis (SUP)
- deep infiltrating endometriosis (DIE)
- ovarian endometriosis (endometriomas, OMA)
The most common type of endometriosis is represented by SUP. This type of lesion involves the peritoneum, a thin layer that covers the inner surface of the pelvic cavity. SUP lesions form flat, shallow patches that do not invade the underlying peritoneum. In contrast, DIE is a specific form of endometriosis that invades tissue and has the potential to metastasize (defined as lesions that infiltrate more than 5 mm under the peritoneal surface). Endometriomas are cystic masses that typically develop deep within the ovaries and account for up to 44% of women diagnosed with endometriosis. These cysts are filled with old blood and are commonly referred to as “chocolate cysts” due to their resulting color.
However, the severity of symptoms or the tendency to progress to malignancy poorly correlates with the defined endometriosis subtypes. Patients with SUP may experience pelvic pain, but chronic pelvic pain and other symptoms like dysmenorrhea, deep dyspareunia, and painful defecation are most strongly associated with OMA and DIE. Therefore, managing OMA and DIE can be more challenging than managing SUP. Additionally, among the three subtypes of endometriosis, only OMA is significantly linked to an increased risk of ovarian cancer. Although DIE exhibits cancer-like local invasive behavior and the ability to metastasize, it rarely progresses to malignancy. Similarly, SUP rarely transforms into malignancy. Current classification systems for endometriosis do not adequately describe the symptoms and prognosis of patients with different endometrial subtypes. Therefore, there is a need to develop a more biologically informative classification system.
Origin of Endometriosis
The origin of endometriosis remains contentious. Researchers have proposed numerous models to explain how endometriosis begins and how endometriotic tissue can grow throughout the abdominal cavity and spread to extrapelvic locations. However, none of these models fully explain the entire spectrum of the disease, and endometriosis development may involve several different mechanisms. Currently, researchers are intensely studying hypotheses such as retrograde menstruation or models involving a stem cell origin. Other theories include benign metastasis through the hematogenous or lymphatic spread of endometrial cells, the transformation of the peritoneal mesothelium (known as “coelomic metaplasia”), and the induction of Müllerian rest.
Endometriosis occurs when eutopic endometrium, including tissue fragments and cells, flows out into the peritoneal cavity during menstruation through the fallopian tubes. The physical displacement of endometrial tissue fragments into the peritoneal cavity during menstruation is explained by Sampson’s theory of retrograde menstruation, which is widely believed to be a major factor in the development of endometriosis. However, retrograde menstruation does not account for the presence of endometrial tissue in extrapelvic locations or in cases where endometriosis develops in individuals without a uterus, such as men taking high doses of estrogen. Theories suggesting a nonuterine origin of the disease, such as coelomic metaplasia and Müllerian remnant differentiation, may offer explanations for these cases. Coelomic metaplasia involves the conversion of normal cells in the peritoneal lining into endometrial cells, possibly triggered by hormonal or immunologic factors.
Stem cell origin theory of endometriosis
Recently, advances in molecular and genetic research have brought considerable attention to the stem cell origin theory of endometriosis. There are two distinct models based on the stem cell’s tissue of origin: stem cells derived from the regenerating uterine endometrium or stem cells derived from the bone marrow. The uterus, the only organ that undergoes repeated cycles of shedding, repair, and regeneration over a woman’s lifetime, is thought to have the capacity for regeneration following menstruation due to adult stem cells located at the endometrial/myometrial interface, also known as the endometrial functionalis layer. This layer persists after menstruation and regenerates the endometrial epithelium during the proliferative phase in response to estrogen.
The first model of stem cell origin postulates that, during menstruation, epithelial stem cells circulating in the body shed from the endometrial functionalis layer intended to regenerate the uterine endometrium. These stem cells may become abnormally activated and trapped outside the uterus. Following retrograde menstruation and trans-tubal migration into the pelvic cavity, this population of adult stem cells may then establish ectopic lesions.
The second model proposes that extrauterine stem/progenitor cells from bone marrow mesenchymal stem progenitors or endothelial progenitors may differentiate into endometriotic tissue. Detecting histologically confirmed endometriotic tissue in women with Rokitansky–Kuster–Hauser syndrome, a rare disorder characterized by the absence of a menstrual endometrium, supports a nonendometrial origin for endometriosis. The stem cell origin of endometriosis may explain the clonality observed in many endometriotic lesions and is consistent with multiple existing theories of endometriosis origin. Endometriosis can arise from endometrial or bone marrow stem cells dispersed via retrograde menstruation, hematogenous/lymphatic dissemination of stem cells, or through persistence in Müllerian rests.
Risk Factors can Endometriosis cause cancer
Genetic Risk Factors
Although researchers still need to fully define the etiopathology of endometriosis, a growing body of research suggests that heritable genetic factors play a vital role in its development and may help explain the different forms of the disease and its manifestations.
Studies in the 1950s first noted a familial clustering of endometriosis, and subsequent research has confirmed the contribution of genetic components to the disease. First-degree relatives of women with confirmed endometriosis have a significantly higher risk of being affected by the disease. Familial cases of endometriosis typically present at an earlier age and have a more severe disease course compared to non-familial cases.
Twin studies have also supported a genetic predisposition to endometriosis, with monozygotic twins at higher risk compared to dizygotic twins.
Endometriosis is a disease that depends on estrogen, and estrogen and estrogen receptor (ER) signaling components play crucial roles in its pathogenesis. Conditions that involve prolonged exposure to endogenous estrogens over a lifetime (such as early menarche or late menopause) and conditions that cause fluctuations in estrogen levels or disrupt menstruation, like a short menstrual cycle, heavy menstrual bleeding, and uterine outlet obstruction, are significant risk factors in all ethnicities. Furthermore, studies on population-based genealogy in various ethnic groups have shown a notably increased risk of endometriosis among individuals of Asian ethnicity.
Modifiable Risk Factors
Diet and lifestyle
Diet and lifestyle modifications can significantly impact the risk of endometriosis by affecting estrogen levels, inflammation, the menstrual cycle, and prostaglandin metabolism. Several studies have demonstrated that individuals who consume a diet rich in green vegetables, fresh fruits, and omega-3 and omega-6 polyunsaturated fatty acids experience a reduced risk of endometriosis. In contrast, individuals who consume diets high in trans fats, coffee, and red meat may have an increased risk of developing endometriosis. Additionally, engaging in physical activity can lower the risk of developing many gynecological diseases, including endometriosis. Furthermore, exposure to endocrine-disrupting chemicals is also a contributing factor to the risk of endometriosis.
Cigarette smoking
Cigarette smoking negatively affects the risk of endometrial cancer. Consequently, researchers have conducted numerous studies on the relationship between smoking habits and endometriosis risk, yielding inconsistent results. Some studies suggest that smoking may reduce the risk of endometriosis possibly due to its antiestrogenic effects. However, other studies have found a positive association or no significant relationship.
Coffee or alcohol
The relationship between coffee or alcohol intake and endometriosis risk remains unclear. Some studies have suggested a protective effect against endometriosis, while others have reported no clear association or opposite trends. Recent studies have identified an association between changes in the composition of the gut and vaginal microbiota and endometriosis, suggesting that microbial dysbiosis could influence the pathology of endometriosis.
The variability in research outcomes likely reflects the complex nature of endometriosis as a multifactorial disease influenced by genetic predispositions, lifestyle factors, and environmental exposures.
Endometriosis as a Neoplastic Disease
Somatic Mutations in Cancer Driver Genes
Although endometriosis is considered a benign disease, it shares striking similarities with cancer. The ectopic endometrial-like epithelium and stroma exhibit neoplastic characteristics, including resistance to apoptosis, stimulation of angiogenesis, invasion, inflammation, and spread, which are typically observed in cancer. These neoplastic characteristics are mirrored by the pathways and gene networks identified in genetic linkage studies. Even more significantly, recent studies suggest that somatic cancer-associated mutations in endometriotic lesions may confer these characteristics, similar to the hallmarks of cancer.
Driver Mutations in Endometriosis cause cancer Development
Although benign endometriotic lesions clearly exhibit nonrandom cancer driver mutations, the specific role of these mutations in endometriosis still remains unclear. These cancer-associated mutations typically regulate cell proliferation, survival, angiogenesis, invasion, and DNA damage repair. Interestingly, similar frequencies of driver gene mutations have been identified in endometriomas, which are believed to be the source of endometriosis-associated ovarian cancer, as well as other subtypes of endometriosis with rare occurrences of malignant transformation. Recurrent somatic cancer driver alterations have been found in all major anatomical subtypes of endometriosis.
Furthermore, researchers have identified the same mutations in both eutopic normal endometrial epithelium and iatrogenic endometriosis, a rare complication linked to laparoscopic supracervical hysterectomy. It is important to note that cancer driver mutations are not exclusive to endometriosis. Studies have revealed somatic driver-like events in over half of the histologically normal endometrial samples examined, as well as in various other normal human tissues.
source of literature from Artical Pathogenesis of Endometriosis and Endometriosis-Associated Cancers
Prevention that can endometriosis cause cancer
It is not known how to prevent endometriosis. Enhanced awareness, early diagnosis, and management may slow. Or halt the natural progression of the disease and reduce long-term burdens of painful symptoms, including potentially reducing the risk of central sensitization. However, there is no cure. Furthermore, there is unacceptably sparse evidence for modifiable risk factors for endometriosis.Large-scale longitudinal studies are critically needed to quantify modifiable exposures in girls and young women in the pre-diagnostic, and ideally the pre-symptomatic, window.
These studies should then explore these exposures further in humans, as well as in experimental models, to determine the physiologic pathways defined by causal effects on the epigenome, transcriptome, proteome, and metabolome.To date, researchers have not robustly replicated few risk factors in multiple populations for endometriosis. The most consistently associated factors include müllerian anomalies, low birth weight and lean body size, early age at menarche, short menstrual cycles, and nulliparity. Less research has supported associations with endocrine disrupting toxins, such as diethystilbestrol. From Artical Pathophysiology, diagnosis, and management of
endometriosis
Sort Fertilization Issue
Can Endometriosis Cause Cancer? sever endometriosis in women can be effectively treated with IVF, which offers a prognosis similar to that of otherwise healthy patients. It is recommended to start IVF treatment as soon as possible due to potential issues with ovarian deficiency. The specific risk of oocytes retrieval should be discussed with the patient. There is no evidence of an increased risk of ovarian cancer in women who undergo IVF and give birth. However, there is conflicting evidence on the impact of IVF on nulliparous women. Parous women with endometriosis may have a slightly higher risk of ovarian cancer, while nulliparous women have a significantly increased risk of cancer. From Artical Endometriosis and Cancer
Conclusions and Future Directions
Endometriosis negatively impacts women’s health and fertility, but it remains a condition that is not well-studied and lacks effective or permanent treatment options due to a lack of understanding of the underlying molecular mechanisms. Population studies have shown a strong hereditary component in endometriosis, with a familial predisposition being associated.However, the polygenic and multifactorial nature of the disease has made it challenging to pinpoint the various genetic effects.
Over the past decade, researchers have conducted studies that have started to reveal the causes and mechanisms of endometriosis. Through linkage and sequencing studies, scientists have pinpointed genes and pathways that play crucial roles in the development of endometriosis, drawing attention to potential connections between endometriosis and endometriosis-associated cancer. Mutations in cancer driver genes have been found to frequently disrupt signaling pathways in both endometriosis. can endometriosis cause cancer making them possible targets for cancer therapy in EAOC.
Although researchers still do not fully understand the molecular basis of how can endometriosis cause cancer, the results obtained so far may benefit clinics by providing a basis for risk stratification. Identifying women with endometriosis who are at risk of cancer development can improve diagnosis and prognosis, likely aiding in enhanced cancer surveillance of at-risk patients in the near future. This has clear clinical significance, as the occurrence of different somatic and epigenetic events may lead to earlier and improved diagnosis and prognosis (biomarkers) and offer targeted treatment options.
