Endometrial cancer is the most common gynaecological malignancy in developed countries. Genetic predisposition and steroid metabolism represent our major research areas in this field. Our final aim is to be able to better predict the prognosis in endometrial cancer, to develop novel treatments and to better counsel women belonging to families with inheritable endometrial cancer. To reach these goals, we are part of the European Network of Individualized Treatment in Endometrial Cancer (ENITEC), a platform where clinicians and scientists from different disciplines meet and discuss together to find novel answers and solutions to the patient’s needs.
Most endometrial tumours are hormone dependent and their growth is sustained by the availability of estrogens in endometrial cancerous cells. However, endometrial tumours develop in most cases after menopause, when the ovaries have already ceased their production of steroid hormones, therefore, the source of estrogens in endometrial cells may derive from in situ metabolic conversions of other circulation steroids. One of our important areas of investigation is the metabolism of steroid hormones in normal and malignant endometrial tissues. We have identified those enzymes that are responsible for the excessive estrogen concentration in the tissue by using our HPLC-based method. We are now trying to understand whether these metabolisms can be exploited in the treatment of endometrial cancer patients; in early diagnosis or in predicting the malignant transformation of initially benign endometrial lesions (hyperplasia); in predicting the prognosis of the patients.
Genetic predisposition in sporadic cases
The PROGINS polymorphism (Reference SNP Cluster Report: rs1042838) in the progesterone receptor has been investigated for any possible association with sporadic cases of endometrial cancer.
Genetic predisposition in familial endometrial cancer
Lynch Syndrome is a hereditary disorder caused by a mutation of one out of four DNA mismatch repair genes (MMR): MLH1, MSH2, MSH6 and PMS2. These genes work in repairing mistakes made when DNA is copied in preparation for cell division.
Carriers of a Lynch Syndrome mutation have an increased risk of developing colorectal cancer (25-75%) and women have to face the additional risk of endometrial (60%) and ovarian (5-30%) cancer, often at a young age.
Cancer sites, risks and age of onset are broad and vary among individuals carrying the same mutation. Hence it is difficult to counsel subjects after a mutation has been detected during a genetic counseling.
The major hypothesis in this research line is that additional genetic factors may modify the cancer risks in carriers of one mutation. The identification of such additional genetic factors would contribute to improve the cancer risk prediction of endometrial and ovarian cancer.
In this project the presence of gene variants that modify/increase endometrial and ovarian cancer risk among members of Lynch Syndrome families is being investigated using cutting edge technologies, like targeted exome capture and next generation sequencing. This study is a collaboration between our team and the department of Clinical Genetics and the Genome Centre in Maastricht.
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