Early-Onset Colorectal Cancer

What is early-onset colorectal cancer (bowel cancer)?

Early-onset colorectal cancer (EOCRC) is colon cancer or rectal cancer diagnosed before the age of 50. It is also known as early age onset CRC and young-onset colorectal cancer. Early-onset CRC accounts for about 10% of colon cancers and 15-20% of rectal cancers.

Since the mid-1990s, the age distribution of colorectal cancer has been shifting. Epidemiology studies show that the incidence of early-onset CRC has been increasing in higher income countries across North America, Europe, Australasia, and parts of Asia. This is in contrast to a decrease in CRC incidence in older adults in high-income countries over the same time period, likely due to increased screening, and therefore, increased diagnosis and treatment of precancerous colorectal polyps, leading to cancer prevention. From 1990 to 2019, global EOCRC cases more than doubled from around 95,000 to more than 225,000.  

In response to the alarming increase in incidence of colorectal cancer in young adults under 50, some organizations, like the American Cancer Society, have updated their screening guidelines. These organizations have lowered the age at which people of average risk should start CRC screening to 45 years old. People with increased risk may begin screening at an even earlier age.

Colorectal cancer screening, including colonoscopy, can prevent cancer, lead to early detection and earlier diagnosis, and prevent cancer deaths.

Why is the incidence of colorectal cancer increasing in younger adults?

While no single cause of the dramatic uptick in early-onset colorectal cancer has been determined, it is likely due to an increase in risk factors. The risk factors most commonly cited are "western" diet, sedentary lifestyle, the metabolic conditions of overweight and obesity, drinking alcohol, and smoking. Each of these factors can affect the bacteria that normally live in the intestines, called the gut microbiome. The balance between the different types of bacteria that make up the gut microbiome affects many aspects of our health and plays a role in starting the formation of colorectal cancer.

Researchers are also studying whether exposure to chemicals in the environment may play a role. These exposures could contribute directly, as in chemicals damaging the DNA of intestinal cells leading to cancer-causing mutations, or indirectly, through chemicals causing risk-increasing metabolic and/or gut microbiome changes.

What are the risk factors for early-onset colorectal cancer?

• diet - eating a "western" diet that is low in fruits, vegetables, and fiber or a diet that is high in fat and processed meats is associated with a higher risk of CRC
• tobacco use - smoking is associated with an increased risk of colorectal cancer
• drinking alcohol (alcohol consumption)  
• lack of regular exercise (physical inactivity, sedentary lifestyle)  
• overweight and obesity  
• inflammatory bowel disease (ulcerative colitis, Crohn's disease, IBD)
• family history of colorectal cancer, especially in a first-degree relative  

If you have any of these risk factors, especially inflammatory bowel disease or a family history of colorectal cancer, you may be at increased risk for EOCRC. Talk to your primary care provider about whether you should be screened.  

Is early-onset colorectal cancer genetic?

Most EOCRC cases are sporadic, meaning they are not due to a known hereditary syndrome. However, compared to colorectal cancer patients over 50 years old, patients with early-onset CRC are more likely to have a genetic predisposition driving their disease. Up to 16-25% of EOCRC patients may have a hereditary genetic syndrome of increased colorectal cancer risk.    

Genetic syndromes are caused by changes (mutations) in your DNA. The genetic cancer syndromes most commonly associated with CRC are Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), which is also associated with several other types of cancer, and familial adenomatous polyposis (FAP), a genetic syndrome characterized by high risk of colorectal polyps occurring at a young age (starting in the teenage years). Of the cases of EOCRC that are due to a genetic syndrome, more than 50% are due to Lynch syndrome and about 20% are due to familial adenomatous polyposis.

If you have a personal and/or family history of previous colorectal polyps, colorectal cancer, endometrial (uterine) cancer, breast cancer, or ovarian cancer, this may suggest the presence of genetic susceptibility (vulnerability) and you should talk to your oncologist about genetic testing. Patients diagnosed before age 50 are recommended to have genetic counseling and evaluation. If you are diagnosed with one of these hereditary syndromes, it is very important to share this information with your biologically related family members. They should have their own genetic testing to find out if they need earlier or more frequent colorectal cancer screening to prevent this disease.  

What are the symptoms of early-onset colorectal cancer?  

The symptoms of early-onset CRC are like the symptoms of any colorectal cancer and include

• change in bowel habits, such as increased or decreased frequency, or a change in the stool (bowel movement) itself  
• constipation  
• diarrhea  
• rectal bleeding
• blood in or on the stool (bowel movement)  
• unintentional or unexplained weight loss  
• abdominal pain or bloating  

If you have any of these symptoms, please talk to your doctor or other healthcare provider.  

What is different about early-onset colorectal cancer?

Advanced disease at cancer diagnosis

Younger patients with CRC are more likely to have advanced stage (stage III or stage IV, metastatic) cancer at the time of diagnosis.    

Prognosis

Patients with early-onset CRC have worse oncologic outcomes than late-onset CRC patients, even patients diagnosed in earlier stages (stage I or stage II).

Tumor location  

Early-onset colorectal cancer is more commonly found in the rectum or the left side of the colon. Tumor location can influence symptoms as well as treatment options.  

Genetics

16-25% of EOCRC cases are related to a genetic syndrome, whereas 5-10% of all colorectal cancers are found to have a known genetic cause.

Pathologic features

Early-onset colorectal cancer is more likely to look a certain way under a microscope, having a mucinous (mucus-producing) and signet ring cell appearance, and more likely to locally invade around nerves, lymphatic vessels, and veins.

Biomarkers

Early-onset colorectal cancers are more likely to exhibit microsatellite instability (MSI, MSI-High), also known as deficient mismatch repair (dMMR). 1 in 6 have MSI-High. Colorectal cancers with MSI-High are particularly susceptible to treatment with immunotherapy. Data on other biomarkers is conflicting, with some studies showing KRAS, NRAS, and BRAF mutations more common in younger age groups and others showing them as less common.

Talk to your oncology team about biomarker testing. Your results may lead you to treatments like immunotherapy, targeted therapy, or investigative therapies through clinical trials.

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