Early-onset colorectal cancer in young individuals

Abstract

Treatment of young adults with colorectal cancer (CRC) represents an unmet clinical need, especially as diagnosis in this population might lead to the greatest loss of years of life. Since 1994, CRC incidence in individuals younger than 50 years has been increasing by 2% per year. The surge in CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. Early-onset CRC are characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left colon-sided location of the primary tumor. Among EO-CRC, approximately 30% of patients are affected by tumors harboring mutations causing hereditary cancer predisposing syndromes, and 20% have familial CRC. Most notably, the remaining 50% of EO-CRC patients have neither hereditary syndromes nor familial CRC, thus representing a formidable challenge for research. In this review article we summarize epidemiology, clinical and molecular features, heredity and outcome of treatments of EO-CRC, and provide considerations for future perspectives.

Keywords: colorectal cancer; familial colorectal cancer; hereditary colorectal cancer; sporadic early-onset colorectal cancer; young adults.

Figure 1

PRISMA 2009 flow diagram depicting the systematic review process performed to retrieve articles on prognosis and RAS and BRAF prevalence among EO‐CRC.

Figure 2

Graphs report age‐adjusted SEER (Surveillance, Epidemiology and End Results) incidence rates of colon (upper panels) and rectal (lower panels) cancer from 1975 to 2015 among individuals younger (left panels) and older (right panels) than 50 years. On the Y‐axis is reported incidence rate per 100 000 and on the X‐axis is reported the year of diagnosis. Data were plotted by accessing SEER website at the weblink https://seer.cancer.gov/faststats/selections.php?series=cancer

Figure 3

Incidence rates increase in colon and rectal cancer in patients younger than 50 years from 2010 to 2030 according to Bailey et al. (2015). Data and projections are confirmed for men and women in the USA). Figures colored in red represent percentages of CRC diagnosed under the age of 50.

Figure 4

Map of the world and countries (shown in red) in which increased incidence of CRC among patients younger than 50 years old has been documented as described in the text (Abou‐Zeid et al., 2017; Ahnen et al., 2014; Bailey et al., 2015; Brenner et al., 2017; Exarchakou et al., 2018; Gandhi et al., 2017; Hessami Arani and Kerachian, 2017; Malekzadeh et al., 2009; A.‐G. Russo, A. Andreano, A. Sartore‐Bianchi, G. Mauri, A. Decarli & S. Siena, personal communication; Troeung et al., 2017; Vuik et al., 2018).

Figure 5

Prevalence of hereditary and familial syndromes, and neither hereditary nor familial syndromes (‘terra incognita’) among EO‐CRC in young individuals. Figures are derived from studies in the text (Bellido et al., 2018; Chang et al., 2012; Fong et al., 2009; Garre et al., 2015; Hahn et al., 2016; Jasperson et al., 2010; Ledermann et al., 2012; Lubbe et al., 2009; Mateo et al., 2015; Mork et al., 2015; Mur et al., 2018; Nejadtaghi et al., 2017; Palles et al., 2013; Pearlman et al., 2017; Robson et al., 2017; Sinicrope, 2018; Stoffel et al., 2018; Umar et al., 2004; Vasen et al., 1991, 1999; Weren et al., 2015, 2018; Yoshida et al., 2017; Yurgelun et al., 2015).