**2.1 Genetic factors**

136 Endometriosis - Basic Concepts and Current Research Trends

alterations in endometrioid cancers of the ovary were analyzed (Catasus L et al, 2004). Frequent alterations are seen in beta-catenin and PTEN genes, as well as MSI in low-stage ovarian carcinomas of endometrioid type. However, allelic loss studies do not provide evidence for the 'endometriosis as tumor' theory (Prowse AH et al, 2005). Ovarian endometriosis with cytological atypia has potential for malignant transformation. Endometriotic cysts seem to be monoclonal and demonstrate aggressive growth and localized invasion of the myometrium. Malignant transformation has been documented. The proposed pathway is through loss of chromosome material by causing allelic imbalance or loss of heterozygosity (LOH).Genomic instability in any form can transform a normal cell to an abnormal or malignant cell. DNA damage can cause genetic alterations and can manifest as gross DNA damage, chromosomal instability or by a more subtle genetic change like

DNA studies examining the role of LOH in endometriotic lesions have identified candidate suppressor gene loci, including 9q, 11q and 22q (Jiang X et al 1996). Alterations in chromosome arms 5q, 6q, 11q and 22q were observed in 25-30% of women with

Gene expression analysis by oligo-nucleotide micro-arrays indicated inflammatory immunoreactions due to up-regulation of FCER1G and PGDS mast cell specific genes which play an important role in producing fibrosis and adhesions in endometriotic lesions (Konno R et al, 2003). Downregulated elements included the tumor suppressor Tp53, genes related to apoptosis, and the gene encoding OVGP1, a protein involved in maintenance of early

Eyster KM et al (2002) illustrated the use of cDNA micro-array technology by studying eutopic endometrium and endometriotic implants from three patients and reported eight genes that were over-expressed in endometriotic implants as compared to eutopic

The revolutionary evolution of genetics and molecular technologies has given a new perspective to the understanding of the etiology of the perplexing disease of endometriosis. Meyer's (1919) hypothesis of coelomic metaplasia in the totipotential peritoneal cells subjected to repeated irritation by a variety of factors, as a cause of endometriosis, would explain those cases of endometriosis in primary amenorrhoea and in men on prolonged estrogen treatment. There are some unknown factors produced within the uterus which stimulate undifferentiated mesenchyme to undergo metaplastic transformation. These *unknown factors* that allow endometrial fragments to implant in the peritoneal cavity of some women and lymphatic spread to allow ectopic endometrium to develop at distant sites are presently being hypothesized to be due to genetic factors. It has been suggested that

Endometriosis is defined as a disease characterized by the presence of functional endometrial cells, comprising of glands and stroma in ectopic sites outside the uterine cavity in addition to their normal presence in the innermost lining of the uterus. The ectopic endometrial tissue

endometriosis and associated carcinoma of the ovary (Jiang X et al 1998).

endometriosis has a genetic basis by Kennedy et al two decades back.

responds to hormones and drugs in a similar manner to eutopic endometrium.

microsatellite instability.

pregnancy (Arimoto et al, 2003).

**1.1 Definition of endometriosis** 

endometrium, that had roles in the cytoskeleton.

Epidemiological data show a familial tendency of endometriosis. Patients with an affected first-degree relative have nearly a ten-fold increased risk of developing endometriosis. Concordance of twins has also been demonstrated (Bischoff FZ et al 2000). There is evidence in both, human and non-human primates that supports the theory of a genetic basis to endometriosis (Zondervan KT et al, 2001).

Attempts to explore the role of genetic and molecular factors in the etiology of endometriosis have begun in the last decade. Genetic studies also detected an association between endometriosis and polymorphic mutations of several genes, including the Nacetyltransferase 2 gene(NAT2), the glutathione S-transferase M gene (GSTM) and Estrogen Receptor alpha gene (ER-a).
