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Whitney F. Jones, M.D. Founder, Coloncancerpreventionproject

This seminar focuses on the evolving features, causes, clinical challenges, and prevention strategies for early age onset colorectal cancer (EAO-CRC). Explore demographic shifts, genetic factors, and diagnostic delays in addressing the rising incidence among the under-50 age group. Learn from experts like Whitney F. Jones, M.D., and understand the importance of early detection for better outcomes.

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Whitney F. Jones, M.D. Founder, Coloncancerpreventionproject

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  1. Early Age Onset Colorectal Cancer: 2018 Implementing ACTION while solving the puzzleIowa Cancer ConsortiumSeptember 24, 25, 2018 Whitney F. Jones, M.D. Founder, Coloncancerpreventionproject.org

  2. Financial Disclosures • Myriad genetics -Consultant and Speaker • Premier Surgery Center of Louisville, Partner • Upstream Health Strategies, Principal Slide acknowledgements: Rebecca Siegel, MPH ACS Dennis Ahnen, MD, University of Colorado Katie Bathje, MPH, Kentucky Cancer Consortium

  3. Learning objectives: EAO-CRC • 1. Understand the evolving features of EAO-CRC including demographics, racial, anatomic, pathologic and clinical outcomes. • 2. Review known and proposed causes of EAO-CRC. • Genetic, familial, environmental ( exosome) • 3. Discuss the major clinical challenges leading to delay in diagnosis. • 4. Explore options to expand the continuum of CRC prevention to the under 50 age group.

  4. BSE first appeared in humans in 1996. 74 people in Britain, 2 in France and 1 in Ireland are dead or dying from mad cow disease

  5. Anatomy of the colorectum (right-sided colon) (left-sided colon)

  6. Incidence trends by age: 50+ versus 20-49 Ages 20-49 Ages 50+ Men Men 51% since 1994 Women Women Source: SEER 9 delay-adjusted rates, 1975-2012; 2-yr moving average.

  7. Age-specific incidence rates by sex 90% of cases Men Women Source: SEER 18 delay-adjusted rates, 2008-2012.

  8. Top 5 cancers, ages 20-49 years Incidence Mortality Men Women Men Women Breast (36%) Thyroid (12%) Melanoma (7%) Colorectum (5%) Cervix uteri (5%) Colorectum (10%) Testis (9%) Prostate (9%) Melanoma (8%) NHL (7%) Breast (26%) Lung (15%) Colorectum (8%) Cervix uteri (7%) Ovary (5%) Lung (18%) Colorectum (12%) Brain (8%) Leukemia (7%) Pancreas (5%)

  9. Subsite distribution by sex and age

  10. Trends in young adults by anatomic subsite 4.8 in 2012 Rectum 2.7% annually since 1991 Proximal colon 2.6 in 1991 Distal colon 2.1% annually since 1994 Source: SEER 9 delay-adjusted rates, 1975-2012; 3-yr moving average.

  11. Trends in young adults by stage at diagnosis Incidence rate per 100,000 3.0% annually, 2003-2012 3.6% annually, 2003-2012 Source: SEER 9 delay-adjusted rates, 1975-2012; 3-year moving average.

  12. Trends in young adults by race/ethnicity Annual % change from 1992-2012 Source: SEER 13 delay-adjusted rates, 1992-2012; 3-year moving average.

  13. Opposing trends within ages 50-59 years -0.8% annually, 2003-2012 -2.7% annually, 2003-2012 55-59 55-59 50-54 50-54 +2.4% annually, 2003-2012 +0.7% annually, 2003-2012 Source: SEER 9 delay-adjusted rates, 1975-2012; 3-yr moving average.

  14. Stage distribution: early vs. later onset Source: SEER 18 registries, 2005-2011.

  15. Five-year relative survival Trend By stage 68% 56% Data Sources: Trends, SEER 9 registries, 1975-2011; Stage-specific, SEER 18 registries, 2005-2011.

  16. Early-onset CRC incidence trends elsewhere 35-39 30-34 25-29 20-24

  17. State variation in incidence rates by age 50+ years 20-49 years

  18. WHY DOES IT OCCUR? Birth Cohort? • Genetic • Familial • Environmental/exosome: • Microbiome • Glyphosate • High fructose corn syrup • Obesity • Oxidative stress • Tobacco [Sleisenger and Fordtran Fig. 123-6]

  19. Hereditary and Familial Colorectal Cancer Sporadic (≈ 70%) Familial (≈ 25%) Rare CRC Syndromes Lynch Syndrome (2-3%) (HNPCC) Familial Adenomatous Polyposis (<1%) Adapted from Burt RW et al. Prevention and Early Detection of CRC, 1996

  20. Young Onset (< 35) Colorectal Cancer Sporadic (≈ 50%) IBD Familial (≈ 20%) Rare Synds Lynch Like Syndrome Lynch Syndrome (12%) Familial Adenomatous Polyposis (8%) Adapted Mork et al J ClinOnc 33; 3544: 2015

  21. Familial Adenomatous Polyposis+ Attenuated FAP • Rare • Autosomal Dominant • High CRC risk ≈100% • Early Onset • Easily recognized • Genetic testing or screening at around age 12 • Surveillance annually

  22. Lynch Syndrome • Autosomal Dominant – 3% of CRCs • High CRC risk- up to 50% • Early onset- 44 yrs • Proximal location- 65% • Other cancers • Under-recognized ≈ 10% • Screening works • Annual colonoscopy • Start at age 25 or 10 years younger than earliest Lynch cancer in the family

  23. EAO-CRC: Deadly delays and misdiagnosisRectal bleeding, abdominal pain, change in bowel habits, and anemia • Patient delays average 6 months • Low CRC awareness under age 50 • Internal Hemorrhoids and IBS common • Symptoms wax and wane • Physician delays in 15-30% • Reluctance to proceed directly to colonoscopy • Poor collection of family history The Increasing Incidence of Young-Onset Colorectal Cancer: A Call to Action Ahnen, Dennis J. et al.Mayo Clinic Proceedings , Volume 89 , Issue 2 , 216 - 224 O’Connell, J.B., Maggard, M.A., Livingson, E.H. et al. Colorectal cancer in the young. Am J Surg. 2004; 187: 343–348

  24. Who else should begin screening before 50?

  25. Overall results: Early-onset cohort • 1 out of 6 (16%)had at least one hereditary cancer syndrome (75 mutations/72 patients) • 1 out of 12 (8.4%)had Lynch syndrome (38*) • 36 (8%) had Lynch syndrome only • 2 (0.4%) had Lynch syndrome plus another syndrome • 1 out of 13 (7.8%)had another syndrome (35*) • 1 patient had two syndromes • Conclusion: Genetic counseling and broad MGPT should be considered for all patients diagnosed <50 years of age, regardless of fhx or MMR tumor status *One patient is counted twice Pearlman et al. JAMA Oncol. 2017;3(4):464-471

  26. 5/17

  27. You don’t have to be a meteorologist to understand your need to get out of a hail storm.

  28. Colonoscopy Rates Are Improving In FDRs But….. Colonoscopy within 10 years FDRs ≥50 Non-FDRs ≥50 Percent FDRs 40-49 Tsai et al. PrevChronic Dis 2015;12:140533

  29. Young Onset (< 35) Colorectal Cancer IBD - 70% have FH of other cancer Sporadic - 10% FDR with CRC - 90% SDR Familial Rare Synds Lynch Like Syndrome Lynch Syndrome (12%) Familial Adenomatous Polyposis (8%) Adapted Mork et al J ClinOnc 33; 3544: 2015

  30. Genetic Counseling Referrals: Drop-out Rate

  31. Lead Time Messaging Normal risk screen High risk screen Age 18 Age 40 Age 50 Message, timing, frequency 1, 3, 7, ?

  32. Timeline of EAO-CRC and Sporadic CRC Messaging Current Message Package 50yr  35-40yr 18yr >75yr

  33. Timeline of EAO-CRC and Sporadic CRC Messaging DONE!! Message Package On Time Message Package On time date + On time options + Early Message Package ID + evaluate symptoms  Family history + test  Lifestyle modification  35-40yr 50yr  >75yr 18yr

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