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Is Cancer Hereditary?

Yes, up to 10% of most cancers are hereditary​. They are caused by genetic changes which can remain asymptomatic until the cancer develops and becomes malignant​. Genetic changes can be inherited from one parent and found in all cells in the body (germline variants)​. Carrying one of these variants can dramatically increase the risk of developing cancer during a person‘s lifetime (autosomal dominant inheritance)​. This risk can be reduced by routine medical checkups and surgery where applicable​.

Genetics of hereditary cancer

Cancer is one of the leading causes of death worldwide and hereditary tumor diseases account for about 5-10% of all cancers. If the genetic modification which predisposes the tumor disease is known, it can be directly detected using a patient sample, as all cells of the organism carry the same genetic modification. Carriers are heterozygous and remain asymptomatic until the second intact allele is spontaneously inactivated by another variant (“second hit”) (“loss of heterozygosity”, LOH). If this occurs in tumor suppressor genes, leads to uncontrolled cell growth and the development of a malignant cell clone. However, spontaneously occurring variants can also lead to the activation of growth factors (protooncogenes), which also leads to uninhibited cell proliferation. In most cases, the risk of developing a tumor during the course of life is very high for carriers of a germline variant. Carriers should be offered frequent screening checks, preventive surgical measures if necessary and psycho-oncological care.

European statistics ​of cancer

  • 1.9 million people in Europe die from cancer each year​
  • 3.9 million new cases of cancer are reported each year​
  • The most common cancer is female breast cancer, followed by colorectal, lung, and prostate cancer​
  • 40% of cancer deaths can be prevented by lifestyle changes ​
  • Up to 10% of cancers have a genetic component​

Why genetic testing for hereditary cancer?

If you or a family member has a predicted high risk of developing cancer, certain actions can be taken to reduce the likelihood of developing cancer. Additionally, family members can be informed and encouraged to have a test or strategies can be implemented for routine monitoring.

Who should get tested for hereditary cancer?

  • You have relatives diagnosed with cancer at a young age <50 years
  • You have a strong family history of the same or multiple different cancer types
  • You have been diagnosed with cancer and would like to know if there is a genetic cause

Common types of hereditary cancer

Common hereditary cancer types include breast or ovarian cancer and colorectal cancer.

Breast & Ovarian Cancer

WHAT: 1 in 3 cancers in women are either breast or ovarian cancer. An average of 5-10% of all breast cancers and of all ovarian cancers are hereditary

HOW: 24% of tested women have pathogenic variants in genes BRCA1 or BRCA2. 6% of tested women have pathogenic variants in the genes CHEK2 (1.5%), PALB2 (1.2%), or RAD51C (1%). <1% of tested women have pathogenic variants in the genes ATM, BARD1, BRIP1, CDH1, NBN, RAD51D, TP53, PTEN, STK11. Pathogenic variants in BRCA1 or BRCA2 can also increase the risk for other cancers, e.g., pancreatic, prostate, and male breast cancer.

MANIFESTATION: Hereditary breast and ovarian cancers are characterized by an early age of onset and/or a high incidence rate in the family.

Colorectal cancer

Colorectal cancer is the third leading cause of cancer death and is the most diagnosed cancer amongst men. It accounts for about 13% of all adult cancers. Europe has one of the highest incidences of colorectal cancer. Up to 10% is hereditary with 2-3% being caused by Lynch Syndrome, also called HNPCC (hereditary non-polyposis colon carcinoma).

Lynch Syndrome: hereditary non-polyposis colorectal cancer (HNPCC)

WHAT: An inherited condition that increases the risk of developing colorectal and other cancers before the age of 50

HOW: Results from monoallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2

MANIFESTATION: Lifetime risk of developing various cancers of the intestines and pelvis

Constitutional Mismatch Repair Deficiency (CMMRD)

WHAT: A distinct childhood cancer predisposition syndrome (also known as Biallelic mismatch repair deficiency – BMMRD)

HOW: Results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2

MANIFESTATION: Broad tumour spectrum: haematological, brain and intestinal tract and Lynch syndrome related tumours

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