Hereditary Colorectal Cancer

Learning that you have colorectal cancer is never easy. Often, the question of ‘how’ is never as important as ‘why’, especially when it shows up much, much sooner than you could have anticipated.

The chance of developing colorectal cancer is influenced by many different risks, and while there are environmental factors such as diet and lifestyle that that we have control over and we can alter the course of neoplastic trajectory, some risk factors cannot be changed but may be influenced by extrinsic factors.

In those with hereditary predisposition for colorectal cancers, germline mutations that are present speed up the process of carcinogenesis in one of many ways. This predisposes these individuals to colorectal cancer, and having these conditions means that the risk of their immediate family developing colorectal cancer is also increased.

It is very important to know that this is not your fault. While major life decisions may play a part, genetic and family history on the whole cannot be avoided, and your diagnosis may even help your family in future.

We hope that a better understanding of hereditary colorectal cancer can empower you and your family when faced with the disease, whether now or in time to come.

We often hear that our personal risk of cancer becomes higher once a family member has been diagnosed, but what does it mean exactly for cancer to be hereditary?

Hereditary colorectal cancer develops as a result of germline mutations that are passed down from parent to child, accounting for 5–10% of all colorectal cancer cases. These mutations happen in the DNA of reproductive cells such as the egg or sperm. As the embryo develops, the mutations from the egg or sperm are incorporated into the DNA of every cell in the offspring's body.

Hereditary colorectal cancer means that the mutations are already present in your cells, even at a young age. This is unlike sporadic colorectal cancer, where the mutations that result in the disease were not always there, but develop later in life.

The genetic mutations manifest in a variety of colorectal cancer syndromes that predispose the individual to colorectal cancers that are often more aggressive with poorer prognosis compared to non-hereditary colorectal cancer. This makes hereditary colorectal cancer difficult to treat, as many of the resultant tumors do not respond well to chemotherapy drugs.

Of the different colorectal cancer syndromes, the two most common ones are Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), and familial adenomatous polyposis (FAP).

If you have been diagnosed with colorectal cancer, you might wonder about your family’s risk and if they too, are likely to be diagnosed. Hereditary colorectal cancer has a few telltale signs that differentiates it from sporadic colorectal cancer.

In most cases of hereditary colorectal cancer, the onset of colorectal cancer symptoms is much earlier than in sporadic colorectal cancer cases. For instance, the age of onset for Lynch syndrome averages at 45 years, while the onset of FAP can be as early as preteen years when colonic adenomas proliferate in the colon. Both of these syndromes manifest much sooner than the sixth decade of their life for sporadic colorectal cancer onset.

Another indicator of hereditary colorectal cancer is family history of not only colorectal cancer but also other cancers. Syndromes such as Lynch syndrome and FAP predispose an individual to colorectal cancer and other cancers.

A thorough compilation of a family’s history of all cancer, including details such as the age of onset, any patterns of multiple primary cancers and any phenotypic or physical characteristics associated with the cancers, can provide an indication of the heredity of cancer within the family.

If heredity is established or individuals test positive for any germline mutations, immediate family members should be encouraged to go for genetic testing and counseling to determine if they are also positive for cancer predisposition.

While no one wants to hear that they are predisposed to having cancer, being aware of it sooner rather than later can be lifesaving.

It is often said that early screening for cancer can save lives, and this is particularly true for hereditary colorectal cancer.

If affected individuals in a family are identified through genetic testing, a targeted cancer surveillance and management plan can be undertaken.

Such plans include:

• Screening schedules commencing at earlier ages and at shorter intervals
• Eliminating the use of other less accurate tests and using only colonoscopy and other scope tests to check for any signs of polyps, adenomas, or tumors

Most importantly, remember that a predisposition to colorectal cancer is not a death sentence. Yes, it will certainly change the way you and your family live and may bring new difficulties. However, an early awareness of familial cancer risk can in fact, reduce morbidity and mortality not only for yourself but your family. So, take heart

because overcoming what’s written in your DNA is absolutely possible.