Cancer risk

If you inherit a genetic mutation, you do not inherit cancer, but an increased risk of developing cancer during your lifetime. Cancer is in fact not a hereditary disease. The risk percentage and type of cancer varies from gene to gene.

While genetic factors and family history of cancer significantly increase the risk of developing the disease, risk is multifactorial. In addition to genetic alterations, endogenous risk factors include: age at menstruations, age at childbirth, age at menopause, and no pregnancy over a lifetime. Among the exogenous risk factors there are: exposure to radiation, carcinogens, and lifestyle (fat intake, alcohol consumption, obesity, smoking).

The tables below present the risk associated with each (mutated) gene and build on the most recent Belgian guidelines on the matter. Based on the risk associated with each gene, risk management guidelines have been drafted. Go to the ‘risk management’ page to find out more.

Cancer risk by gene mutation

 

Table 1 – High penetrance genes

 BRCA1BRCA2PALB2
Breast (women)60 – 80 % (higher risk for triple negative breast cancer)60 – 80 %30 – 60 % (depending on family history)
Contralateral breast cancer40% within 20y20-25% within 20yIncreased
Ovarian cancer40%20%5-15% (depending on family history)
Breast cancer (men)1%7%1%
ProstateModerately increased15% before 65 y/
PancreasSmall but increased risk5-10%2-3%

Table 2 – Moderate penetrance genes

CHEK2 ATM RAD51C and RAD51D BARD1 BRIP1 MLH1, MSH2, MSH6
Breast cancer (women) 20-45% (depending on family history) Around 30% (depending on family history) 20-45% (depending on family history / Higher risk for triple negative breast cancer) 20-45% (depending on family history / Higher risk for triple negative breast cancer) / /
Ovarian cancer / 5-10% / 5-10% 5-15% (depending on mutated gene)
Breast cancer (men) 0,5-1% 0,5-1% / / / /
Prostate cancer Moderately increased Moderately increased / / / /
Pancreas cancer / / / / / /
Colorectal cancer / / / / / 20 – 60%
Endometrial cancer / / / / / 15-70% (depending on mutated gene)

Different from the hereditary breast and ovarian cancer syndrome, the Li-Fraumeni syndrome (LFS) is linked to a mutation in the TP53 gene. LFS is characterised by:

  • a strong familial aggregation of cancers
  • early-onset of tumours
  • wide tumour spectrum, including the so-called core LFS cancers: soft-tissue sarcomas (STS), osteosarcomas, adrenocortical carcinomas (ACC), central nervous system (CNS) tumours and very early-onset female breast cancers, occurring before 31 years.
Although estimating the cancer risk (or penetrance) associated with each specific TP53 variant is challenging, recent studies and guidelines agree that:
  • in childhood, the main tumour risks are adrenocortical carcinomas, soft-tissue sarcomas, osteosarcomas and central nervous system tumours;
  • the main tumour risk in adults corresponds to female breast cancers. Female carriers have an excessively high risk of developing breast cancer before 31;
  • there is no known elevated risk of male breast cancer.

Do you think you may have a hereditary predisposition to cancer?

Visit the genetic testing page.