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Definition
All cancer is genetic -- mutations in genes involved in cell growth and divisions cause cancer. But cells have two copies of these genes. Both copies have to break in order to form cancer. A person can inherit an already broken copy and then have one break, or just have both copies break, to develop cancer.
This only applies to tumor suppressor genes, not proto-oncogene. |
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| What are the major classes of cancer genes? |
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Definition
1. Tumor suppressor genes
2. Proto-oncogenes
3. Other genes/Gatekeepers (ie, genes that help maintain the integrity of the DNA during replication) |
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These genes encode proteins that inhibit cell growth. If they break, cancer will form. BRCA are examples of this.
They are “dominant inheritance” (ie, if your mom has a broken one you inherit that dominantly) but recessive on a system level -- you need two breaks to get cancer. Retinoblastoma is another example. |
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These genes encode proteins that promote cell growth. If they get stuck “on” they are called oncogenes and cause cancer.
Examples are growth factors. They are rarely inherited. The two hit hypothesis DOES NOT apply to them -- if they are stuck on, they form cancer. |
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Definition
One of the major classes of cancer genes. These are genes that help maintain the integrity of the DNA, ie, they might help with mismatch repair.
If they break it is easier for other genes to break and for cancer to form. |
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Definition
| Breast cancer originating from the ducts that is still noninvasive. Considered cancer for a risk assessment (though you might add five years to the age -- ie, in five years this would be cancer). |
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| Lobular carcinoma in situ |
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Definition
| Breast cancer originating from the lobes of the breast that is non invasive. This is actually NOT considered cancer for a risk assessment. |
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| Early stage cancer that is still in the original site. It is still noninvasive. |
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| Invasive ductal carcinoma |
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Definition
| A breast cancer that is invasive and started in the ducts. This is about 80% of breast cancer and the type seen in most hereditary syndromes. |
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| Invasive lobular carcinoma. |
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Definition
| This is about 15% of invasive breast cancers. People who get these cancers are more likely to get bilateral cancer. |
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| What are some rare types of breast cancer? |
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Definition
1. Inflammatory breast cancer (that causes the breast to be warm, red, and swollen)
2. Medullary carcinoma (has a very distinct boundary between tumor and flesh)
3. Mucinous carcinoma (cancer that produces mucus)
4. tubular carcinoma (similar to ductal)
5. Paget’s disease (epidermal cancer of the nipple)
6. Phyllodes tumors (breast cancer arising from the connective tissue) |
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| How much of breast cancer is hereditary? |
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Definition
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| What are “clues” that a family’s cancer might be hereditary? |
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Definition
-Two or more first or second degree relatives that are affected
-autosomal dominant pattern of inheritance
-early ages of onset (under 45-50)
-bilateral or multiple site cancers
-similar or related cancer types (ie, breast and prostate)
-triple negative cancer
-male breast cancer
-ethnic background associated with a high incidence of mutation (Ashkenazi Jewish) |
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Definition
| Tumor suppressor genes involved in DNA repair. They help with “cell checkpoints” before replication. They are one of the major causes of hereditary breast cancer and ovarian cancer. They also cause a risk for prostate cancer and pancreatic cancer. However, we can’t actually give a hard number about how much having a mutation in these genes increases your risk. |
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Definition
A classic but rare hereditary cancer syndrome associated with the TP53 gene.
Autosomal dominant.
There is a 50% risk of cancer by 40, 90% by 60. These cancers are usually breast (frequent in women), and the kinds of cancers usually seen in children (like bone, soft tissue sarcomas, brain cancers, and leukemia).
Adrenocortical tumors are fairly specific to this syndrome as are malignant phyllodes tumors.
There is a risk of multiple primary cancers and a risk of radiation-related secondary cancers. Someone with this syndrome follows the “toronto protocol” of whole body MRI screening. |
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Definition
Rare hereditary cancer syndrome associated with the PTEN gene.
Autosomal dominant.
These cancers are usually mucocutaneous lesions. They can happen on the face, lips, tongue, or the oral mucosa. There is also a lifetime risk of breast cancer, thyroid cancer, endometrial cancer, and renal cancer. This is also a colon cancer syndrome.
To diagnose this, look out for macrocephaly and a history of breast cancer, thyroid cancer, and skin tags. Intellectual disability is also telling. |
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AUTOSOMAL RECESSIVE neurodegenerative syndrome that causes severe disability. They also have a high risk of radiation-induced cancer.
Being a carrier for the ATM gene is also a cancer syndrome.Female carriers have an elevated risk of breast cancer. There is not enough evidence to say radiation affects them similarly. |
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PALB2 stands for Partner and Localizer of BRCA2. It is autosomal dominant.
Causes an increased risk of breast cancer and pancreatic cancer. Really think about this gene with pancreatic families. |
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| CHEK2 stands for Checkpoint Kinase 2. It is part of the BRCA pathway. It causes an increased risk of breast cancer but is more like a risk factor/moderate penetrance. We know this because people can have two mutations. |
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An autosomal recessive hereditary cancer disorder that is tied into the BRCA pathway. You need to inherit two broken copies of BRCA1.
People with this disorder can have physical differences, such as short stature, and often have bone marrow failure or leukemia. |
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| Also called hereditary diffuse gastric cancer syndrome. It is associated with an increased risk of lobular breast cancer and gastric cancers. |
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Having two NBN mutations is associated with Nijmegan (pronounced knee-ma-gin) breakage syndrome.
This is an autosomal recessive disorder that causes growth retardation, immunosuppression, and cancer risk. Heterozygotes have an increased risk of breast cancer. |
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STK11 gene. Higher penetrance risk of breast cancer (50% lifetime risk) and GI hamartomas. Also a colon cancer syndrome.
This has characteristic pigmentation of the lips -- it looks like they have spots of blue-black ink. |
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Term
| What are the standard “high penetrance” breast cancer genes? |
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Definition
| BRCA1, BRCA2, TP53 (Li-Fraumeni Syndrome), PTEN (Cowden syndrome), STK11 (Peutz-Jeghers Syndrome) |
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| What tips you off it might be BRCA1? |
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Definition
| More triple negative cancers |
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| What tips you off it might be BRCA2? |
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| A protein blood marker for ovarian cancer. Not very specific. |
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