Young-Onset Colorectal Cancer: Is It Time to Pay Attention?

The 2010 Annual Report to the Nation on Cancer celebrated a steady decline in the incidence of colorectal cancer (CRC).¹ This progress has been largely attributed to CRC screening, recommended for adults 50 years or older since 1996.² In sharp contrast to overall trends, the incidence of CRC appears to be increasing among adults younger than 50 years,^1,3 a group for whom average-risk screening is not routine. Particularly concerning is a trend toward advanced-stage CRCs,^1,3 suggesting a potential role for increased clinical vigilance and more prompt evaluation of symptomatic patients. To raise clinical awareness and facilitate recognition, we undertook a cohort study to (1) examine incidence trends; (2) define the distinct clinicopathologic manifestations of young-onset CRC; and (3) identify risk factors for advanced-stage disease.

We used the National Cancer Database (NCDB), a hospital-based cancer registry sponsored by the American College of Surgeons and American Cancer society that captures 70% of all incident cancers annually.⁴ We identified patients diagnosed as having invasive adenocarcinoma (behavior code 3 [malignant]; histology codes 8010, 8020-8022, 8140-8144, 8210-8211, 8260-8263, 8470-8473, 8480-8481, and 8490) of the colon and the rectum between January 1998 and December 2007, the most recent decade after the US Preventive Services Task Force (USPSTF) recommended CRC screening. Eligible patients (n = 588 869) were stratified by tumor site (colon [site codes C180, 182-189, and 199] vs rectum [site code C209]) and by age at diagnosis (young onset [before age 50 years] vs later onset [at age 50 years or older]). Age-adjusted incidence rates (per 100 000 individuals) were calculated using the 2000 US standard population (SEER*Stat software, version 7.0.4; National Cancer Institute). The temporal trend in the annual percentage change (APC) was identified (Joinpoint Regression Program, version 3.5.1; National Cancer Institute). For a subgroup (n = 34 781) of young-onset CRCs diagnosed between 2003 and 2007—the following years after the USPSTF strengthened its screening recommendation in 2002⁵—independent predictors of advanced-stage disease (stages III and IV, nodal and distant metastatic disease) were identified by multiple logistic regression. This study was granted exemption status by The University of Texas MD Anderson Cancer Center institutional review board.

We identified 64 068 young-onset (10.9%) and 524 801 later-onset (89.1%) CRCs. Age-adjusted incidence declined for later-onset CRCs after 2001 (APC, −2.5%; 95% CI, −3.0% to −2.0%) but has consistently increased since 2001 for young-onset disease (APC, 2.1%; 95% CI, 1.1% to 3.1%). The increase was greater for young-onset rectal (APC, 3.9%; 95% CI, 3.1% to 4.7%) than colon (APC, 2.7%; 95% CI, 2.0% to 3.3%) cancers. The median age for young-onset CRCs was 44 years, with most (75.2%) occurring between ages 40 and 49 years. Compared with later-onset disease, young-onset CRCs were more prevalent among patients with nonwhite race/ethnicity (29.5% vs 17.6%; P < .001), who were not insured or insured by Medicaid (16.5% vs 4.7%; P < .001) and who lived in the southern and western parts of the United States (56.2% vs 50.3%; P < .001). Young-onset CRC more commonly arose from colon distal to the splenic flexure or the rectum (69.0% vs 57.7%; P < .001). Mucinous and signet-ring histologic subtype (12.6% vs 10.8%; P < .001) and poor or no differentiation (20.4% vs 18%; P < .001) were also more frequently exhibited. Advanced-stage disease was diagnosed significantly more commonly in young patients (Table). Independent risk factors for advanced-stage disease included younger age (age 30-39 years: hazard ratio [HR], 1.21; 95% CI, 1.1 to 1.4; age 18-29 years: HR, 1.4; 95% CI, 1.2 to 1.6; vs age 40-49 years); African American race (HR, 1.2; 95% CI, 1.1 to 1.3; vs white race) and lack of insurance or Medicaid insurance (uninsured: HR, 1.2; 95% CI, 1.1 to 1.3; Medicaid: HR, 1.6; 95% CI, 1.5 to 1.8; vs insured).

This cohort study of young-onset CRC, the largest to date, highlights an alarming rise in incidence since 2001. Most worrisome is the high proportion of stage III/IV disease (Figure), consistent with a prior smaller population-based report.¹¹⁰⁰¹⁵ In the absence of routine screening, contributing factors to these trends may include (1) a reluctance on the part of young adults to seek medical care⁷; (2) the large percentage of young adults without insurance or ready access to care (18.3%-29.2% for adults aged 18-44 years vs 1.3%-13.6% for adults older than 45 years⁸); and (3) an underappreciation of the increasing risk for young-onset CRC, leading clinicians to overlook or dismiss symptoms that are nonspecific but may be consistent with CRC (ie, rectal bleeding, abdominal pain or cramping, change in bowel pattern). Finally, the predilection of young-onset CRCs for the distal colon and rectum identify these as high-yield anatomic regions for endoscopic evaluation in symptomatic patients and as potentially cost-effective targets for screening programs in presymptomatic young adults.

This study could not establish the mechanisms underlying observed sociodemographic disparities, nor did it explore the molecular basis of young-onset CRC (familial adenomatous polyposis was excluded). Notwithstanding, these data argue for heightened awareness of these concerning trends in young-onset CRC. Symptomatic young patients should undergo timely sigmoidoscopy at a minimum, if not a full colonoscopy. Identifying high-risk cohorts for targeted screening should be a priority.

Correspondence: Dr You, Department of Surgical Oncology, Unit 1484, University of Texas MD Anderson Cancer Center, 1400 Pressler St, PO Box 301402, Houston, TX 77230-1402 (ynyou@mdanderson.org).

Published Online: December 12, 2011. doi:10.1001/archinternmed.2011.602. This article was corrected for an error in the Figure key on December 13, 2011.

Author Contributions: Dr You had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of data analysis. Study concept and design: You, Xing, Chang, and Cormier. Acquisition of data: You, Xing, and Cormier. Analysis and interpretation of data: You, Xing, Feig, Chang, and Cormier. Drafting of the manuscript: You and Cormier. Critical revision of the manuscript for important intellectual content: You, Xing, Feig, Chang, and Cormier. Statistical analysis: You, Xing, and Cormier. Obtained funding: You and Cormier. Study supervision: Feig and Cormier.

Funding/Support: This study was supported by the University of Texas MD Anderson Cancer Center Institutional Research Grant (Dr You) and The University of Texas MD Anderson Cancer Center's Institute for Cancer Care Excellence.

Previous Presentation: This study was presented in part at the Sixth Annual Academic Surgical Congress, Association for Academic Surgery; February 4, 2011; Orange County, California.

Additional Contributions: Miguel A. Rodriguez-Bigas, MD, and John M. Skibber, MD, assisted with critical revision of the manuscript, and Yan K. Ling, MPH, assisted with data analysis.