In Germany almost half a million people develop cancer every year. Currently malignant tumours are the second most common cause of death worldwide. Due to demographic trends, the number of new cancer cases will increase by 20% until 2030. Fortunately, significant progress was achieved concerning screening for and treatment of tumour diseases, particularly for breast and colorectal cancer.
In general, genetic as well as environmental factors contribute to the development of tumours. In some cancers such as retinoblastoma, a malignant tumour of the retina, genetic factors are of paramount importance. In other tumour types external factors play the leading role, e. g. smoking in lung, bladder and larynx cancer. Genetic factors are considered to be the main causative factor in only 5 to 10% of all cancers.
In non-hereditary cancers, a normal somatic cell initially transforms into a cancer cell step by step. In the course of a lifetime every cell of the body will unavoidably accumulate changes of the DNA, so-called somatic mutations. Some of these alterations affect genes which are essential for regulating cell growth (proto-oncogenes) or repairing DNA damage (tumour suppressor genes). With increasing age, the probability to develop cancer constantly rises. Main causes for these DNA alterations are cosmic and UV radiation, tobacco smoke, alcohol and metabolites such as free radicals. A healthy lifestyle may counteract some of these factors, and consequently reduce cancer risks.
Indications for hereditary cancer
Familial clustering of cancers may indicate that hereditary factors play an important role for cancer development in such families. Consequently, some members of such families may be prone to specific cancers due to an individual hereditary disposition, consisting of mutations in proto-oncogenes or tumour suppressor genes. However, such mutations do not occur in the course of a lifetime in a single cell of the body (somatic mutation) as is the case in non-hereditary cancers. In contrast, it is present in every cell of the body, originating from a mutation in the zygote (germline mutation). In most cases, this mutation has been inherited from one parent. Nevertheless, it occasionally occurs de novo during oocyte or sperm cell development.
Proto-oncogenes and tumour suppressor genes are not equally important in every tissue of the body. In every tissue, cell growth regulation and DNA repair depend on a unique set of proto-oncogenes and tumour suppressor genes. Consequently, mutation carriers of these genes are at risk only for specific tumour types. For some of them they bear a high risk, for others they have a more or less lower or only an average risk – the basis for tailored schedules of screening measures. Moreover, for organs with high risks prophylactic removal can be an option (for instance, removal of the thyroid is recommended for the hereditary form of medullary thyroid cancer).
Genetic diagnostics and screening measures
Important indicators for a hereditary cancer are an early age of onset, occurrence of the same or typical associated cancers in the index patient or in several members of the family and repeated occurrence of the same tumour type in the same individual. Recently, in some tumours also specific properties of tumour tissue can give useful hints (for instance, loss of expression of mismatch repair gene products in Lynch syndrome). Most hereditary cancers are inherited in an autosomal dominant manner. However, in some entities other modes of inheritance can be observed, e. g. autosomal recessive inheritance in MUTYH-associated polyposis, a special type of hereditary colorectal cancer.
The tumour risk may be variable. In some cancer syndromes, it may reach nearly 100%. In most tumour syndromes, however, it is much lower. Genetic counselling and molecular genetic diagnostics for hereditary tumours represent a focus and an area of particular expertise at the Senckenberg Centre for Human Genetics. Examples are Hereditary Breast- and Ovarian Cancer (HBOC), the different types of hereditary colorectal cancer (e. g. HNPCC/Lynch syndrome, FAP, MAP), Hereditary Diffuse Gastric Cancer (HDGC) and rare entities such as Li-Fraumeni and Cowden syndrome. Unveiling the responsible mutation in an individual can be of paramount importance since it enables targeted preventive screening measures in this individual. Additionally, it is an essential prerequisite for offering predictive testing to further members of a patient’s family. Finally, in recent years the knowledge of the disease-causing mutation has gained importance for individual treatment in some tumour entities.
Further special expertise
Hearing loss is the most common sensory deficit in humans, affecting approximately 1 in 500 newborns. Deafness has a genetic basis in two-thirds of patients.
Inherited eye diseases
Many eye diseases have a genetic basis. The knowledge of the underlying gene defect has far-reaching consequences for the individual medical care and guidance of patients and their families.
Malignant hyperthermia (MH) is a hereditary metabolic myopathy triggered by certain anaesthetics. The molecular genetic testing in patients with suspected MH and the predictive genetic testing of at-risk asymptomatic family members enables an accurate diagnosis with just a blood sample.
Disorders of the nervous system
Numerous disorders of the nervous system may be due to genetic causes and they may be part of a syndrome affecting other organs. A genetic diagnosis may avoid stressful examinations and pave the way for an anticipatory disease management or even therapeutic options.