Hereditary colorectal cancer

GeneMate

How common is colorectal cancer?

About 7000 people get diagnosed with colorectal cancer in Sweden each year1, which makes it the third most common cancer in Sweden. A majority of 75% are diagnosed at 65 years of age or older. Colon cancer is equally common in men and women, while rectal cancer is more common in men.

What causes colorectal cancer?

About two thirds of all colorectal cancer is caused by DNA damage, which can occur during DNA replication or be due to environmental factors. DNA damage occurs all the time and most of the time it is repaired. But with age comes an accumulation of DNA damage, and in turn a higher likelihood that a normal cell transforms into a cancer cell. Age is therefore the leading risk factor for cancer.

The remaining one third of all colorectal cancer is explained by hereditary factors2. The impact of hereditary factors on the risk of developing cancer can range from small to very large. Individuals with a hereditary colorectal cancer syndrome, which is caused by a single pathogenic variant (mutation), constitute two to four percent of all hereditary cases. These individuals are born with a DNA variant in all their cells, usually located in a gene involved in DNA repair. As a result, the ability to protect cells from becoming cancer cells is impaired and cells therefore have a higher probability of becoming cancer cells. The remainder of hereditary colorectal cancer cases are classified by a certain family history of colorectal cancer but lack an underlying pathogenic variant. Healthy individuals with an increased risk of hereditary colorectal cancer are recommended a single colonoscopy at 55 years age or colonoscopy every five years starting five years before the age of the youngest onset in the family. 

Hereditary colorectal cancer syndromes

There are two groups of hereditary colorectal cancer syndromes:

  • Polyposis syndromes – Characterized by the presence of a large number (up to 1000) of polyps in the colon and rectum. These polyps can become colorectal cancers if not removed. Polyposis syndromes include:
    • Familial adenomatous polyposis(FAP)
    • MUTYH associated polyposis (MAP)
    • Peutz-Jeghers syndrome (PJS)
    • Juvenile polyposis (JP)
    • Cowden syndrome (PTEN, hamartomatous polyposis syndromes)
  • Lynch syndrome – Differs from the polyposis syndromes by the absence of a large number of polyps and was previously named hereditary nonpolyposis colorectal cancer (HNPCC). Lynch syndrome is also associated with an increased risk of cancer in other parts of the body, such as the uterus.

The GeneMate® test includes analysis of the following genes associated with the above syndromes:

SYNDROME

GENES

Familial adenomatous polyposis(FAP)

APC

MUTYH associated polyposis

MUTYH

Peutz-Jeghers syndrome (PJS)

STK11

Juvenile polyposis (JP)

PTEN, SMAD4, BMPR1A

Cowden syndrome

PTEN

Lynch syndrome

EPCAM, PMS2, MLH1, MSH2, MSH6

Healthy individuals that are carriers of pathogenic variants in any of the above-mentioned genes can decrease their cancer risk through preventive measures. The Swedish health care system offers colonoscopy to individuals with Lynch syndrome every other year from age 20 to 25 onwards. Those with a polyposis syndrome are offered yearly colonoscopy from age 12 to 15 until the number of polyps are becoming too large, at which point removal of the colon and rectum is recommended.

GeneMate® offers you a comprehensive risk assessment through the combination of a genetic test as well as an evaluation of your family history.

 

ORDER

 

Anna Hellquist, Genetic Counselor at iCellate Medical AB, PhD Cell and Microbiology

 

References

  1. Nationellt vårdprogram tjock- och ändtarmscancer – RCC Kunskapsbanken. https://kunskapsbanken.cancercentrum.se/diagnoser/tjock-och-andtarmscancer/vardprogram/. Accessed January 10, 2021.
  2. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland. New England Journal of Medicine. 2000;343(2):78-85.
  3. https://sfmg.se/download/riktlinjer/Cancergenetik/NVP-Tjock-och-andtarmscancer_2020-03-25-Arftlig-tjocktarmscancer.pdf