HNPCC
Meaning of HNPCC: The inherited cancer syndrome named for the polyps it does not produce, now generally called Lynch syndrome for exactly that reason.
Definition of HNPCC
HNPCC stands for hereditary nonpolyposis colorectal cancer, an inherited condition caused by a fault in one of the genes that proofread DNA after it is copied. Carriers face a much higher lifetime risk of bowel cancer, and raised risks of cancer of the womb lining, ovary, stomach, small bowel and urinary tract. It is now generally known as Lynch syndrome.
What goes wrong in the cells?
Every time a cell copies its DNA it makes mistakes, and a proofreading team goes over the new strand repairing mismatched letters. Someone with this condition inherits one faulty copy of a gene belonging to that team. Each cell still holds a working spare, so nothing happens until that spare fails in some individual cell, which grows more likely with time. From then on the cell copies its DNA uncorrected, and errors pile up fastest in short repeated stretches of sequence that are easy to slip on. Tumors arising this way carry a recognizable signature of unstable repeats, which is how the laboratory identifies them, and the same heavy error load makes them unusually responsive to drugs that unleash the immune system.
Why is the name misleading?
Nonpolyposis was chosen to separate the condition from an inherited disease in which the bowel carries hundreds or thousands of polyps. People with this condition do form polyps; they simply form the ordinary small number. What differs is speed, since a single polyp can progress to colorectal cancer within a few years rather than over a decade or more, and the growths favor the right side of the colon, which is harder to reach and to see. That mismatch between name and reality is why Lynch syndrome has largely replaced it.
Which cancers become more likely?
| Site | Note |
|---|---|
| Colon and rectum | The highest risk, often on the right side |
| Lining of the womb | Frequently the first cancer to appear in women |
| Ovary, stomach, small bowel | Raised, though well below the bowel risk |
| Urinary tract, pancreas, brain | Raised in some families and with some genes |
| Skin | Sebaceous tumors mark a recognized variant |
Which gene is affected changes both the pattern and the level of risk, so the syndrome is not one uniform condition across families.
Also known as
Used in a sentence
Tumor testing showed loss of a mismatch repair protein, prompting assessment for HNPCC.
Good to know
The nonpolyposis in the name refers to the absence of the hundreds of polyps seen in familial adenomatous polyposis, not to an absence of polyps, and individual polyps in this condition progress to cancer unusually quickly.