Abstract
The aim of this review article was to evaluate the relationship and the possible etiological mechanisms between endometriosis, leiomyoma (LM) and adenomyosis and gynecological cancers, such as ovarian and endometrial cancer and leiomyosarcoma (LMS). MEDLINE was searched for all articles written in the English literature from July 1966 to May 2013. Reports were collected systematically and all the references were also reviewed. Malignant transformation of gynecologic benign diseases such as endometriosis, adenomyosis and LM to ovarian and endometrial cancer remains unclear. Hormonal factors, inflammation, familial predisposition, genetic alterations, growth factors, diet, altered immune system, environmental factors and oxidative stress may be causative factors in carcinogenesis. Early menarche, low parity, late menopause and infertility have also been implicated in the pathogenesis of these cancers. Ovarian cancers and endometriosis have been shown to have common genetic alterations such as loss of heterozygosity (LOH), PTEN, p53, ARID1A mutations. MicroRNAs have also been implicated in malignant transformation. Inflammation releases proinflammatory cytokines, and activates tumor associated macrophages (TAMS) and nuclear factor kappa b (NF-KB) signaling pathways that promote genetic mutations and carcinogenesis. MED12 mutations in LM and smooth muscle tumors of undetermined malignant potential (STUMP) may contribute to malignant transformation to LMS. A hyperestrogenic state may be shared in common with pathogenesis of adenomyosis, LM and endometrial cancer. However, the effect of these benign gynecologic diseases on endometrial cancer should be studied in detail. This review study indicates that endometriosis, LM, adenomyosis may be associated with increased risk of gynecological cancers such as endometrial and ovarian cancers. The patients who have these gynecological benign diseases should be counseled about the future risks of developing cancer. Further studies are needed to investigate the relationship between STUMPs, LMS and LM and characteristics and outcome endometrial carcinoma in adenomyotic patients.
Highlights
Gynecologic cancers lead to high morbidity and mortality rates around the world
This review study indicates that endometriosis, LM, adenomyosis may be associated with increased risk of gynecological cancers such as endometrial and ovarian cancers
This review shows that endometriosis, LM and adenomyosis are at significantly increased risk for the development of gynecological cancers such as ovarian cancer and endometrial cancer
Summary
Gynecologic cancers lead to high morbidity and mortality rates around the world. A total of 790,740 new cancer cases and 275,370 deaths from cancer in women are projected to occur in the United States in 2012 (Siegel et al, 2013). Many factors have been associated with the increased risk, especially in ovarian and endometrial cancers such as hormonal factors, inflammation, familial predisposition, genetic alterations, growth factors, diet, altered immune system, environmental factors and oxidative stress. Some demographic factors such as early menarche, low parity, late menopause and infertility have been implicated in the pathogenesis of these cancers. Endometriosis, adenomyosis and uterine myomas are benign diseases that commonly affect the women of reproductive age. All of these ‘womb’ diseases are known to be estrogen dependent benign tumors. This review would discuss the evidence that suggests correlations between these diseases and ovarian and endometrial cancers
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