Rising incidence of colorectal cancer in Millennials – time for a paradigm shift?

Dr. Dhruvin Hirpara is a General Surgery resident at the University of Toronto

Dr. Nancy Baxter is a colorectal surgeon at St. Michael's Hospital

Dr. Fayez Quereshy  a surgical oncologist at the University Health Network.

 

Colorectal Cancer (CRC) is the second leading cause of cancer-related death amongst men, and the third leading cause of cancer-related death in women in Canada. Although screening has contributed to declining incidence in the elderly, recent epidemiological data reflect a rise in CRC among young adults. Data from the Canadian Cancer Registry suggest a steady increase in young-onset (15-49y) CRC, from 745 cases in 1969 to 1475 cases in 2010. In Ontario, the incidence of CRC has been increasing in young adults (30-49y) since 2005, from 6.17 per 100,000 to 9.08 per 100,000 for colon cancer, and 4.31 per 100,000 to 6.29 per 100,000 for rectal cancer. Evidence from other jurisdictions, including France, Australia, and the United States reflects similar trends in the rise of young-onset CRC. Why this apparent increase in CRC among younger people? We don’t yet know the cause but theories point to an interplay of several potential factors.

One reason may be increased colonoscopy use in younger adults. One study showed colonoscopy in this age group increased by ~30%  between 2001 and 2009. So earlier detection through screening (i.e. lead-time bias) may be playing a part, since the study showed that mortality rates remained relatively stable during this period.

The rise in young-onset CRC has also coincided with the obesity epidemic. The authors of a meta-analysis of prospective studies postulated that the rate of CRC increases about 20% with every five unit increase in BMI (kg/m2); another study suggested that up to 48 % of the increase in CRC incidence among young Caucasian adults has been due to increased BMI. Obesity could promote CRC development via numerous pathways including stimulation of low‐grade inflammation and oxidative stress with increased levels of pro-inflammatory molecules that contribute to mutagenesis.

Other theories include the increased prevalence of well-established risk factors among young adults including diet (such as eating processed meat and red meat), sedentary lifestyle, diabetes, smoking and excessive alcohol consumption.

A growing body of evidence suggests that bacterial imbalance in the gut, known as Dysbiosis, also plays an important role in the development of CRC. The abovementioned factors, including obesity, elements of a western diet, and lack of exercise have all been shown to shift the gut microbiota towards a less diverse, more pro-inflammatory carcinogenic profile.

Young-onset CRC has also been shown to be more aggressive in nature. This may be attributable to its distinctive biology and genetic profile in this population. Younger patients tend to have less stage I or II disease, more stage III or IV disease and worse-grade tumors. Poor histologic subtypes, associated with worse outcomes, are common in young-onset CRCs. These features, combined with failure to recognize colonic symptoms (see below), may be detrimental to long-term survival in young patients with CRC. Although Canadian data are yet to mature, US data appear to show that young patients (20-40y) with CRC have a poorer overall 5-year survival compared with their older (60-80y) counterparts (61.5% vs 64.9%; P=0.02); stage-specific survival rates in patients with young-onset CRC, however, equal or exceed those of their counterparts with later-onset CRC.

The difficulty is that because CRC is still a relatively infrequent diagnosis  in young people (despite its rising incidence), and it is traditionally seen as a disease of older adults, recognition of symptoms and discovery of the disease is often delayed for younger people. What about screening? Currently, adults younger than 50 years without risk factors are not recommended to undergo routine screening for CRC. When diseases aren’t common but have devastating consequences it is a good idea for physicians to maintain a low threshold for further investigations. Particularly the finding that 85% of millennials with CRC are symptomatic at diagnosis, should prompt consideration of CRC in a young person with symptoms consistent with possible CRC e.g., rectal bleeding.  “Red-flag” symptoms and signs for CRC include persistent rectal bleeding, changes in bowel habits, abdominal pain and anemia. Remember that stool-based screening tests are for use in asymptomatic average-risk individuals to detect unsuspected disease and aren’t the best choice when working up a patient who has symptoms and in whom CRC is suspected. A thorough workup including endoscopy, which may require prompt referral to another specialist provider (i.e. gastroenterologist or surgeon), is a better choice for the patient with symptoms.

This disconcerting observed rise in incidence of young-onset CRC should prompt further research into possible causes. In the meantime, physicians would do well to promptly investigate all patients with suggestive symptoms, irrespective of age. Clinical prudence and proactive testing could mitigate premature morbidity and mortality. And don’t forget that risk reduction strategies, which apply to patients of all ages, including counselling on smoking cessation, alcohol intake, weight loss and exercise may also help mitigate the burden of young-onset CRC.

Leave a Reply

Your email address will not be published. Required fields are marked *