Dr. Pal Moller

Oslo University Hospital, Oslo, Norway


Oslo University Hospital, Oslo, Norway

Title: “Inherited Cancer”

Abstract:

Adult onset cancer is a function of age, which means that we all have a  probability to contract cancer each year we live. This probability  varies with gender and age and is influenced by environmental factors.  From the previous belief that cancer was caused by growth-genes  (oncogenes), it was clarified that these genes could not be better  functioning than when normal, the problem was the regulatory systems  turning them on and off. In short, the problem is that growth genes has  to be turned off to control cell growth. These downregulating genes are  referred to as supressor genes. With very few exceptions, inherited  cancer is in-borne defects in supressor genes, with the consequence that  cellular growth is not downregulated and cellular growth becomes out of  control, which is the cause of a tumour leading to cancer. The  consequence is that persons born with such genetic defects have a higher  probability per year to contract cancer. In early embryonic life cells are destined to become different types of  tissues, and all their offspring cells will have all other genetic  information made unavailable. The different tissues are using different systems of supressor cells to regulate cell growth. In consequence,  inborn errors in given supressor gene will have different impact on  cancer probability in different organs. When an organ is dependent on  one system and have no very good back-up mechanism if this system fails, the person with a genetic inborn defect in that system will have an  increased risk of cancer in that organ. The BRCA1/2 genes, despite being  functional in all our cells every day, this way increase the risk for  breast cancer and ovarian cancer when deranged. In contrast, the  mismatch-repair genes MLH1, MSH2 and MSH6 – despite being instrumental  in all our cells every day – increase the probability for  gastrointestinal and gynaecological cancer when deranged.