An action plan to address the rising burden of colorectal cancer in younger adults

Figures & data

Table 1. Known colorectal cancer risk and protective factors: risk estimate, change in population prevalence in adults <50 years of age in recent decades.

	Risk estimates	Change in prevalence
Risk factors
Hereditary syndromes	4.0+	NC
Family history of CRC	2.0+	NC
Family history adenoma	2.0+	UK
Obesity	1.2–1.5	I
Sedentary lifestyle	1.3 (colon)	NC
Binge drinking	1.6	NC
T2DM	1.4 (colon) 1.2 (rectal)	I
Smoking	1.2	D
Processed meat	1.2	I
Crohn’s disease	2.6	NC
Ulcerative colitis	1.9–2.8	NC
Protective factors
Aspirin use	0.3	D
Diet (fruit/vegetables)	0.9	UK

For risk estimates, data was taken from [28–37,44,45,47]. For change in prevalence, data was taken from [38–43,46,49,50].

CRC: Colorectal cancer; D: Decrease; I: Increase; NC: No change; T2DM: Type 2 diabetes mellitus; UK: Unknown.

Table 2. Potential novel risk factors and new hypotheses for early-onset colorectal cancer.

Exposure/risk factor	Genetics	Timing of exposure	Cancer site
Antibiotic use Food additives Gut microbiome Vaccines Birth weight Pesticides Insulin resistance HPV Helicobacter pylori Sleep patterns Recreational drug use New smoking products Decreased exposure to aspirin	Lower penetrant mutations Epigenetic alterations Gene–environment interactions	In utero Early childhood Adolescence Teens Early adult	Colon – Distal vs proximal Rectum

Table 3. Objective 1: accelerate research to address unanswered questions about early-onset colorectal cancer.

Priorities: What do we need to know/do?	Strategies: How can we do this?	What resources are available or needed?	Who needs to be engaged?
What is the cause of the rising incidence of EOCRC? • What is role of known RFs? • What is role of novel /proposed RF? • Do RF differ by site, i.e., colon vs rectum? • Are there vulnerable times of exposure related to risk for EOCRC? • How has prevalence of RFs changed? • What if any is the impact of changes in clinical practice on EOCRC (e.g., medications, screening, colonoscopy use) • Is EOCRC molecularly different than CRC in older adults? If so, what does it tell us about causation? • What is the role of epigenetics?	• Conduct prospective case–control studies nested within existing cohort or large health system with EMR • Conduct retrospective case–control studies • Convene group of top epidemiologists to design study and write proposal	Available: • Existing cohorts (CCFRC, CPS-3, ARIC-CA, Millennium Cohort Study) • Other cohorts; Nurses’ Health Study, Physicians Study • Childhood cohorts linked with cancer registries (Natl longitudinal survey of youth, 1970 British Cohort Study, Greater Boston Otitis Media Study) Needed: • New funding Access to EHR data from health systems	• Academic partners • Integrated healthcare systems like Kaiser or VA or large hospital groups with EMRs • Center for Microbiome Research • Funding agencies: NCI, ACS
What is the natural history of EOCRC? • What is the prevalence of adenomas in younger adults? • What is rate of progression from adenoma to carcinoma in younger adults? • What is the screening regimen that will optimize reduction in incidence and mortality of EOCRC?	• Collect colonoscopy data from screened individuals of all ages and indications for screening • Data modeling • Review existing colonoscopy databases • Compare average age of adenoma, advanced adenomas and CRC in cohort of first colonoscopy in 45–49 years olds	Available: • GIQuIC, the New Hampshire Colonoscopy Registry and other endoscopic databases • The German colonoscopy screening database Needed: • 45–49 years-old screening registry	• Gastroenterology groups • CISNET • Other modeling groups
What are best practices for implementing current recommendations for identifying and managing EOCRC?	• Randomized-controlled trials or pragmatic trials within clinic or healthcare systems • Learn from on-going studies	Available: • Moonshot request for applications • CDC Public health genomics states • Tumor registries Needed: • Common evaluation metrics	• Healthcare systems • Providers: oncology, primary care, genetic counselors • Public health • Tumor registry
What research is on-going that may answer some of these questions?	• Search NCI, NIH, ACS-funded grants • Survey national and international experts/groups involved in this work	Available: • Search databases for NCI, NIH, ACS Needed: • Intern/fellows/staff to reach out to investigators and collate information	• NCI, ACS, NCCRT • Patient advocacy groups • Insight investigators • On-going cohort investigators

ACS: American Cancer Society; ARIC-CA: Atherosclerosis Risk in Communities Cohort; CCFRC: Colon Cancer Family Registry Cohort; CDC: Centers for Disease Control; CISNET: Cancer Intervention and Surveillance Modeling Network; CPS-3: Cancer Prevention Study; CRC: Colorectal cancer; EOCRC: Early-onset colorectal cancer; EMR: Electronic medical record; EHR: Electronic health record; GIQuIC: GI Quality Improvement Consortium; NCCRT: National Colorectal Cancer Roundtable; NCI: National Cancer Institute; NIH: National Institute of Health; RF: Risk factor; VAMC: Veterans Administration Medical Centers.

Table 4. Objective 2: increase adoption of evidenced-based practices to identify and manage persons at risk for early-onset colorectal cancer.

Priorities: What do we need to know/do?	Strategies: How can we do this?	What resources are available or needed?	Who needs to be engaged?
Provider level
Improve provider education about EOCRC • Rising incidence of EOCRC • Signs and symptoms of EOCRC • Separate screening versus diagnostic recommendations for colonoscopy	• Disseminate Family History and EOCRC Provider Toolkit • Develop/disseminate CMEs • Engage provider groups • Engage payers in developing quality measures • Create educational campaigns directed to providers	Available: • Family History and EOCRC Provider Toolkit • NCCRT and ACS education resources • Existing CMEs Needed: • New messages to alert providers	• Provider professional societies • Primary care groups • Medical liability/malpractice insurers • Payers • NCCRT/Jackson Laboratories • Advocacy groups • Other guideline groups
Improve screening adherence in young adults: • Lynch syndrome: age 25 or younger, annually • Moderate risk due to family history: age 40 or younger; every 3–5 years • Population: age 45, every 10 years	• Integrate risk-based screening messages into EMR • Develop new messages to alert patients and providers	Available: • Family History and EOCRC Provider Tool Kit • NCCRT and ACS educational resources Needed: • Evaluation of Toolkit	• ACS, CDC • Primary care groups • Screening providers • Public health • Advocacy groups
Patient level
Improve population awareness of • The importance of family history as a risk factor for CRC • The recommendations for earlier screening based on family history of CRC or advanced adenomas • The risk and symptoms of EOCRC	• Media campaigns • Social media • New apps for phone/tablets	Available: • Existing campaigns Needed: • New messages with marketing plan	• Public health • Patient advocacy groups; Fight CRC, Colon Cancer Alliance; Colon Cancer Challenge Foundation
Improve uptake on referrals for risk assessment	• Utilize patient navigators • Remove barriers: insurance, discrimination, cost, fear • Expand use of tele-counseling services	Available: • Tele-counseling services • Counseling via laboratories Needed: • Streamlined referral systems • Better communication between providers, patients, counselors • Coordinated care for high risk	• Genetic counselors • Physicians • Healthcare systems • Payers
Systems level
Improve collection and use of family history (CRC and polyps) in primary care in younger adults to inform screening and referral for risk assessment	• Enhance EMRs; collect family history of CRC and adenomas and integrate provider alerts • Integrate risk assessment tools into practice • Promote use of patient portals • Develop clinical guidelines and quality measures for workup of common symptoms for EOCRC	Available: • Jackson Labs, NCCRT, CMEs • EMR vendors willing to collaborate Needed: • Easy-to-use, validated risk assessment tools	• Primary care providers and professional organizations • EMR vendors • NCCRT • ACS-CAN WG on EMR and family history
Increase adoption of universal tumor testing for LS and cascade screening	• Educate health systems • Include in CoC accreditation	Available • EGAPP recommendations • Implementation guides Needed: • New incentives to adopt universal tumor testing for LS • Institutional commitment	• Healthcare systems • Pathology departments • CoC • Cancer centers • ACS, CDC Office of Public Health Genomics

ACS-CAN: American Cancer Society Cancer Action Network; CDC: Centers for Disease Control; CME: Continuing Medical Education; CoC: Commission on Cancer; CRC: Colorectal cancer; EGAPP: Evaluation of Genomic Applications in Practice; EMR: Electronic medical record; EOCRC: Early-onset colorectal cancer; LS: Lynch syndrome; NCCRT: National Colorectal Cancer Roundtable.

Table 5. Objective 3: solidify commitment from engaged and new partners to move plan into action.

Priorities: What do we need to know/do?	Strategies: How can we do this?	What resources are available or needed?	Who needs to be engaged?
Provide forum for on-going discussion of issues related to EOCRC	• Support and participate in the annual NYC EAO-CRC Summit (www.coloncancerfoundation.org) • Support other advocacy group efforts to address EOCRC	Available: • NCCRT infrastructure and staff • Advocacy groups and staff Needed: • Coordination and communication • Goodwill	• NCCRT, ACS • Advocacy groups
Publish a collaborative paper or white paper with NCI, ACS, CDC with unified statement	• Get support from entire group • Recruit writing committee	Available: • NCCRT member expertise • Links with NCI, ACS and CDC Needed: • Resources, enthusiasm, leadership	• NCI, ACS, CDC • Lead author(s) • NCCRT content experts
Engage healthcare systems in setting national research agenda around EOCRC	• Identify champions within several systems • Promote implementation research; identify specific opportunities	Available: • Outline of research priorities (from Plan) Needed: • Implementation Scientists • Leadership/commitment from healthcare systems	• Healthcare systems leadership • Experts in EOCRC research • Implementation scientists
Convene the leadership of the professional societies (internal medicine, family practice, GI, GYN, general surgery, etc.) to formulate strategies to work on the problem	• Facilitate national meeting of key stakeholders • Identify champions to move work forward	Available: • Society membership charters and rosters Needed: • Interest, enthusiasm, champions	• Professional societies • NCCRT • Experts in quality metrics • Payers

ACS: American Cancer Society; CDC: Centers for Disease Control; CRC: Colorectal cancer; EAO-CRC: Early-age onset colorectal cancer; EGAPP: Evaluation of Genomic Applications in Practice; EOCRC: Early-onset colorectal cancer; GYN: Gynecology; NCCRT: National Colorectal Cancer Roundtable; NCI: National Cancer Institute.

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