The Link Between Endometriosis and Cancer

Tuesday, 22/06/2010  |   Ovarian/ Uterine Cancer  |  no comments

Endometriosis, like cancer, is characterised by cell invasion and unrestrained growth. Furthermore, endometriosis and cancer are similar in other aspects, such as the development of new blood vessels and a decrease in the number of cells undergoing apoptosis. In spite of these similarities, endometriosis is not considered a malignant disorder. The possibility that endometriosis could, however, transform and become cancer has been debated in the literature since 1925. Mutations in the genes that encode for metabolic and detoxification enzymes, such as GALT and GSTM, have been implicated in the pathogenesis of endometriosis and in the progression to carcinoma of the ovary (Swiersz 2006). PTEN, a tumour suppressor commonly mutated (50%) in endometrial carcinoma, is found mutated in endometrioid carcinoma of the ovary, but not in other forms of ovarian cancer. There are data to support that ovarian endometriosis could have the potential for malignant transformation. Epidemiologic and genetic studies support this notion. It seems that endometriosis is associated with specific types of ovarian cancer (endometrioid and clear cell) (Vlahos et al, 2010). The relationship between endometriosis and ovarian cancer is an intriguing and still poorly investigated issue. Specifically, histological findings indicate a definitive association between endometriosis and endometrioid/clear cell carcinoma of the ovary (Parihar & Mirge 2009).
A recent study has shown that somatic mutations in the PTEN gene were identified in 20% of endometrioid carcinomas and 20.6% of solitary endometrial cysts, suggesting that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma. In addition to cancerous transformation at the site of endometriosis, there is recent evidence to indicate that having endometriosis itself may increase a woman’s risk of developing non-Hodgkin’s lymphoma, malignant melanoma, and breast cancer (Swiersz 2006).
Women with endometriosis appear to be more likely to develop certain types of cancer. Brinton, PhD, Chief of the Hormonal and Reproductive Epidemiology branch at the National Cancer Institute has studied the long-term effects of endometriosis, which led her to Sweden about 20 years ago. Using the country’s national inpatient register, she identified more than 20,000 women who had been hospitalised for endometriosis.[1] After an average follow-up of more than 11 years, the risk for cancer among these women was elevated by 90% for ovarian cancer, 40% for hematopoietic cancer (primarily non-Hodgkin’s lymphoma), and 30% for breast cancer. Having a longer history of endometriosis and being diagnosed at a young age were both associated with increased ovarian cancer risk (Brinton et al, 1997).
Farr Nezhat, MD, Chief of Gynecologic Minimally Invasive Surgery and Robotics at St. Luke’s and Roosevelt Hospitals in New York City and Professor of Obstetrics and Gynecology at Columbia University, spoke on the pathogenesis of endometriosis and ovarian cancer. He said studis suggest that alterations in bcl-2 and p53 may be associated with the malignant transformation of endometriotic cysts (Nezhat et al, 2002). Dr. Nezhat also cited research on the link between epithelial ovarian cancer and endometriosis. According to a 2000 study of women with ovarian cancer by Hiroyuki Yoshikawa and colleagues, endometriosis was present in 39% of the women with clear cell tumours and 21% of those with endometrioid tumours, vs just 3% of those with serous or mucinous tumours. Endometriosis may be the precursor of clear cell or endometrioid ovarian cancer (Yoshikawa et al, 2000).
If you combine inflammation with oestrogen as with both endometriosis and ovarian or uterine cancers, it’s going to be a vicious circle, as the 2 diseases share numerous other characteristics. For example, both are related to early menarche and late menopause, infertility, and nulliparity. Factors that relieve or offer protection against both conditions include tubal ligation, oral contraceptives, hysterectomy, and progesterone exposure.
Some authors also suggest that there is an also increased risks of colon cancer, ovarian cancer, thyroid cancer non-Hodgkin’s lymphoma and malignant melanoma in women with endometriosis when compared with the general population (Brinton et al, 2005).

Brinton, L.A., Gridley, G., Persson, I., Baron, J. & Bergqvist, A. Cancer risk after a hospital discharge diagnosis of endometriosis. 1997 American Journal of Obstetrics and Gynaecology. Volume 176, Issue 3, Pp. 572-79
Brinton, L.A., Moghissi, K.S., Scoccia, B., Westhoff, C.L & Lamb, E.J. Ovulation induction and cancer risk. Fertil Steril(2005) 83, b. Pp.261–74
Nezhat, F., Cohen, C., Rahaman, J., Gretz, H., Cole, P. & Kalir, T.Comparative immunohistochemical studies of bcl-2 and p53 proteins in benign and malignant ovarian endometriotic cysts. 2002 Cancer Vol 94 Issue 11, Pp. 2935-40. DOI 10.1002/cncr.10566
Parihar, M. & Mirge, A. Cancer in Endometriosis. pp.80-2 2009 In Endometriosis; An Enigma. Purandare, C.N. & Kriplani, A. Eds.
Swiersz, L. M. Role of Endometriosis in Cancer and Tumour Development. 2006 Annals of the New York Academy of Sciences. Vol 955. Endometriosis: Emerging Research and Interventions Strategies. Pp. 281-92
Vlahos, N.F., Economopoulos, K.P. & Fotiou, S. Endometriosis, in vitro fertilisation and the risk of gynaecological malignancies, including ovarian and breast cancer. 2010 Clinical Obstetrics and Gynaecology. Vol 24, Issue 1, Pp. 39-50
Yoshikawa, H., Jimbo, H., Okada, S., Matsumoto, K., Onda, T., Yasugi, T. & Taketani, Y. Prevalence of endometriosis in ovarian cancer. Gynecol Obstet Invest. 2000;50(suppl 1):Pp.11-7.

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