Early-Onset Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer in the world and is a leading cause of morbidity and mortality.1 In the United States, it is associated with the third highest number of new cancer diagnoses and cancer-related deaths each year.2 Although CRC is often thought to be a disease of the elderly population, the incidence in this age group has been declining over the past 30 years.3 This decline has been largely attributed to improved and more robust screening practices, including routine colonoscopies in patients aged 50 years, or the traditional screening age. Despite these gains made in older patients, the percentage of young patients diagnosed with early-onset CRC (EOCRC) has been steadily increasing since the 1990s.4 The cut-off age for EOCRC is not strictly defined but is generally denoted as all CRCs diagnosed in patients younger than 50 years. There are a large number of studies on hereditary causes of young-onset CRC, such as Familial Adenomatous Polyposis and Lynch Syndrome. However, 3 of 4 individuals with EOCRC have no familial history at all.5 Recently, owing to the trends of increasing sporadic cases, the American Cancer Society has lowered the recommended age for initial polyp screenings for average-risk individuals from age 50 to 45 years.6 These worrying trends have also inspired countless studies aimed at uncovering the unique characteristics and clinicopathologic mechanisms underlying EOCRC as well as the factors contributing to the sharp increase in cases. Studies have revealed EOCRC as a distinct biologic disease from late-onset CRC (LOCRC) with its own molecular, genetic, and histopathologic characteristics.7 EOCRC is known to demonstrate patterns of invasive, aggressive behavior and overexpresses specific genes when compared with LOCRC.8 These unique features can be used to aid in early diagnosis, prognosis, and disease course monitoring that is specific to EOCRC. They can also serve as targets of current and future treatments. Risk factors that have been implicated in EOCRC development include genetic