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Is cancer hereditary?


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Is cancer hereditary?

Many cancers run in the families and the immediate relatives (siblings, parents, and children) of patients with cancers often have an increased risk of cancers. I will try to explain this with the help of specific examples to make it more easily understandable.

Breast cancer is an example in which immediate relatives may have a higher risk of breast cancer or other types of cancers. Sometimes the increased risk may be due to a genetic mutation. BRCA1 and BRCA2 are examples of genetic mutation that gives rise to increased risk of breast cancer. Women who have this mutation have about 60% lifetime risk of developing breast cancer. Women with these mutations also have significantly higher risk of developing ovarian cancer. This mutation is genetically transmitted to off springs in an autosomal dominant model. This means that son or daughter of BRCA mutation carrier has 50% risk of acquiring the mutation. It is to be noted that only about 5% breast cancers belong to this category where a specific genetic mutation can be identified. Apart from identifiable genetic mutation that increases the risk of breast cancer, presence of a family member with breast cancer would increase the risk of development of breast cancer in a woman.

Unlike patients who are carriers of well-recognized genetic mutations like BRCA1 or BRCA2, these women do not have any evidence of genetic alterations that would increase the risk of breast cancer. The increased breast cancer risk in this group of women may be related to a group of genes rather than a single gene mutation. These genetic alterations as a group may have increased predisposition to development of breast cancer. It is also difficult to separate environmental factors in these patients. The role of environmental factors is difficult to quantify in this situation and how much of this increased risk is caused by common environmental factors is difficult to judge. If a woman, say Miss A has a first degree relative (mother, daughter, or sister) with diagnosis of breast cancer, the risk of Miss A developing breast cancer is 1.7 times higher (called relative risk) compared to the general population. If that first-degree relative of Miss A had developed breast cancer prior to the menopause, the relative risk for Miss A would be 3 fold. On the other hand if that relative had breast cancer after menopause, the relative risk for Miss A would be 1.5 fold. If that relative had developed bilateral breast cancer then the relative risk for Miss A would be 5 fold higher. Again if that relative who developed bilateral breast cancer had developed the breast cancer prior to menopause, the relative risk for Miss A would be 9 fold higher. You can see here complex factors playing roles to increase the risk of breast cancer.

A similar situation is present in colon cancer as well, there are specific identifiable genetic mutations that gives rise to very high risks of developing colon cancer. Mutation in the APC gene is a noted example. If a person carries this mutation that person has close to 100% risk of developing colon cancer in the late adulthood. This gene is transmitted in an autosomal dominant model, which means that any offspring of the carrier has a 50% risk of inheriting this mutation and subsequent increased risk of colon cancer. As with breast cancer most cases of colon cancer are not related genes that could be tested. Colon cancer diagnosis in a person would increase the risk of colon cancer development in his close relatives. Again as mentioned above this is not the result of a single genetic abnormality that is inherited, but is really due to interaction of a group of genes and various environmental factors common to the family like eating habits and food preferences.

Most of the familial cancers are multi-factorial and most of the time there are no demonstrable genetic markers or patterns. A small percentage of the cancers can be truly genetic with identifiable genetic markers. The pattern of familial clustering is more in some cancer like breast cancer, colon cancer, and ovarian caner but less in many other types of cancers like lung cancer, prostate cancer, and esophageal cancer.

The following is a list of identified familial genetic syndromes associated with a single genetic abnormality. Please not that this is not a comprehensive list of all known disorders.

Autosomal dominant disorders
BRCA1: Breast cancer BRCA2: Breast cancer
APC: Colon cancer HNPCC: Colon cancer
CDKN2: Melanoma  
Basal cell nevus syndrome Neurofibromatosis type 2
Carney syndrome Osteochondromatosis, multiple
Chordoma, familial Paraganglioma, familial
Cowden syndrome Peutz-Jeghers syndrome
Esophageal cancer with tylosis Prostate cancer
Gastric cancer, familial Renal cancer, familial
Li-Fraumeni syndrome Retinoblastoma
Multiple endocrine neoplasia type 1 Tuberous sclerosis
Multiple endocrine neoplasia type 2 von Hippel-Lindau disease
Neurofibromatosis type 1 Wilms' tumor

Autosomal recessive disorders
Ataxia-telangiectasia Rothmund-Thomson syndrome
Bloom syndrome Xeroderma pigmentosa
Werner's syndrome Fanconi's anemia

Cancer terms:
In vitro: In vivo is something that is done in a test tube or laboratory. Cancer cells are often grown in tissue cultures on plates or test tubes. Studies are done on these cells to see how they grow and react. If some one says drug A has been found effective in preventing multiplication in vitro that means drug A was found to do this on cells growing in some laboratory. See cancer terms for more cancer related terms.

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