Risk Factors for Early-Onset Colorectal Cancer

Colorectal cancer, which occurs in the large intestine of the digestive tract, is the third most common type of cancer around the world (excluding non-melanoma skin cancers). Fortunately, its incidence and death rate have decreased in the United States and the European Union over the past two decades, largely because of the popularization of screening programs for older adults that allow for the detection of precancerous legions. Whereas previously, the US Preventive Services Task Force recommended that screenings begin at age 50, a growing body of evidence has shown a concerning increase in early-onset colorectal cancer, prompting the task force to lower the recommended age to 45 in May of 2021. The new guidelines reflect a 2018 recommendation from the American Cancer Society that screening begin at 45 years old.²

It is not fully understood why colorectal cancers appear to be increasing in younger populations. In 2010, 5 percent of colon cancers and 9 percent of rectal cancers occurred among patients younger than 50 years of age; a decade later, these figures had increased to 11 percent and 15 percent, respectively.² Overall, since 1994, colorectal cancer incidence is estimated to have increased by 2 percent per year in young adults,³ with the youngest cohorts (those 20 to 29 years old and 30 to 39 years old) seeing the greatest increases.² Notably, approximately one-half of early-onset colorectal cancer patients have neither hereditary syndromes (such as Lynch syndrome) that predispose them for cancer nor a history of colorectal cancer in the family, which has challenged researchers to identify the environmental or lifestyle factors that may be contributing to the disease.³

Common risk factors for poor health are associated with increased risk of colorectal cancer. These include smoking, low physical activity, heavy alcohol intake, unhealthy diet, and overweight or obesity.^4,5 Researchers have hypothesized that a “Western lifestyle” — characterized by many of these risk factors — may be partially responsible for the increase in early-onset colorectal cancer in successive birth cohorts since the 1980s. The accumulation of these risk factors, alongside increasing exposure to antibiotics and chemicals, especially in neonatal and early developmental stages, may contribute to genetic and epigenetic alterations in colorectal epithelial cells, while also impacting the gut microbiome. There is significant evidence that changes to the gut microbiome may stimulate colorectal cancer, with past research highlighting the influence of F. nucleatum and Bifidobacterium bacteria. Exposures affecting the microbiome may accumulate throughout different life stages, making it plausible that changes to the microbiome may be associated with rising rates of early-onset colorectal cancer, but nonetheless difficult to elucidate exactly how.⁶

Early-onset colorectal cancer is also associated with specific demographic features: its incidence has been relatively high among Black individuals for several decades (12.7 cases per 100,000 people), and recently, its incidence in white individuals has been rising to nearly these levels. In addition, lower household income and educational levels, as well as rural residence, have been associated with increases in colorectal cancer incidence and mortality.⁶

Researchers have aimed to identify interventions that may lower risks of colorectal cancer. Daily low doses of aspirin (75-300mg) have been shown to reduce the long-term incidence and mortality of colorectal cancer. This may especially be the case for cancers of the proximal colon, which are not otherwise effectively avoided with colonoscopy or sigmoidoscopy.⁷

In addition, a July 2021 study in Gastroenterology was the first of its kind to suggest that high intake of vitamin D from dietary sources (as opposed to supplements) may be associated with lower incidence of early-onset colorectal cancer or precancerous colon polyps in women. The study authors note that in the past several decades, there has been a decline in vitamin D intake from dietary sources such as fish, mushrooms, eggs, and milk. While it is still unknown why early-onset colorectal cancer is increasing, the researchers posit that higher vitamin D intake could be an inexpensive complement to screenings as an effective prevention strategy.⁸

Overall, screening remains one of the most effective ways to prevent early-onset colorectal cancer. According to some models, those with high risk scores (generated by taking into consideration eight risk factors) may benefit from beginning screenings six to seven years earlier than the recommended age of 45.⁴ Researchers have proposed various ways to remove barriers for screenings, such as providing paid leave.² Still, to fully address rising rates of colorectal cancer in younger populations, researchers will need to further uncover direct causes and specific risk factors. By harnessing the techniques of precision medicine, physicians can identify young patients with the greatest risks and optimize the delivery of preventive care.²

References

Stigliano V, Sanchez-Mete L, Martayan A, Anti M. Early-onset colorectal cancer: a sporadic or inherited disease? World J Gastroenterol. 2014;20(35):12420-12430. doi:10.3748/wjg.v20.i25.12420

Ng K, May FP, Schrag D. US preventive services task force recommendations for colorectal cancer screening: Forty-Five is the new fifty. JAMA. 2021;325(19):1943-1945. doi:10.1001/jama.2021.4133

Mauri G, Sartore-Bianchi A, Russo A-G, Marsoni S, Bardelli A, Siena S. Early-onset colorectal cancer in young individuals. Mol Oncol. 2019;13(2):109-131. doi:10.1002/1878-0261.12417

Wang K, Ma W, Wu K, et al. Long-term colorectal cancer incidence and mortality after colonoscopy screening according to individuals’ risk profiles. J Natl Cancer Inst. Published online 2021. doi:10.1093/jnci/djab041

Hannan LM, Jacobs EJ, Thun MJ. The association between cigarette smoking and risk of colorectal cancer in a large prospective cohort from the United States. Cancer Epidemiol Biomarkers Prev. 2009;18(12):3362-3367. doi:10.1158/1055-9965.EPI-09-0661

Akimoto N, Ugai T, Zhong R, et al. Rising incidence of early-onset colorectal cancer – a call to action. Nat Rev Clin Oncol. 2021;18(4):230-243. doi:10.1038/s41571-020-00445-1

Rothwell PM, Wilson M, Elwin C-E, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376(9754):1741-1750. doi:10.1016/S0140-6736(10)61543-7

Kim H, Lipsyc-Sharf M, Zong X, et al. Total vitamin D intake and risks of early-onset colorectal cancer and precursors. Gastroenterology. Published online 2021. doi:10.1053/j.gastro.2021.07.002

Risk Factors for Early-Onset Colorectal Cancer

Related posts: