1. Colorectal Cancer: Update on Screening and Hereditary Colon Cancer
Priyanka Kanth, MD, MS, FACG
Assistant Professor
University of Utah Healthcare
Huntsman Cancer institute
Salt lake city, utah

2. Aim Colon cancer statistics
Overview of Colon polyps, colon cancer and hereditary cancer syndromes.
Risk factors of colon polyps and colon cancer.
Recognition of hereditary GI cancer syndromes.
Prevention and surveillance of colon cancer and hereditary cancer syndromes.

3. Colon Cancer Statistics
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in United States.
CRC is the third most common cancer in men and women.
2018- An estimated 140,250 new cases of CRC cases are expected to be diagnosed.
2018- An estimated 50,630 deaths are expected to occur from CRC cancer.
American Cancer Society

4. Colon Cancer Statistics
Lifetime risk of CRC- 5%
Colorectal cancer (localized disease)- 5 years survival is 90%.
39% of cases are diagnosed at the localized stage.
Advanced cancer stage- 5 year survival can be as low as 12%.

5. Colorectal cancer Sporadic - 70% Hamartomatous polyposis <1%
Familial-25%
FAP <1%
Lynch syndrome: 1-3%
Burt. Gastroenterology 2010

6. Colon Polyps

7. Colon polyps Classification
New addition (WHO 2010)
Pre-neoplastic
(20-30% of CRC)
Benign
Pre-neoplastic (70% of CRC)
Hyperplastic Polyp
Tubular Adenoma
Villous Adenoma
Sessile Serrated Polyps

8. WHO Classification of Serrated Colon Polyps (2010)
1. Hyperplastic Polyp -Microvesicular HP (MVHP) -Goblet cell HP (GCHP) Not used clinically -Mucin poor HP (MPHP) 2. Sessile Serrated Adenoma/Polyp (SSA/P) -SSA/P without cytological dysplasia -SSA/P with cytological dysplasia (uncommon) 3. Traditional Serrated Adenomas (TSA)- rare
Snover D, et al. WHO Classification of Tumors of the Digestive System IARC, Lyon, 2010

9. Sessile serrated polyps
Sessile serrated polyps (SSA/P & TSA):
20-30% of CRC may develop via serrated pathway.
Morphology may vary.
Prevalence ranges from 2-7%.
Mostly found in the proximal colon (SSA/P).
Considerable Inter and Intra-observer variability among pathologists.
Increased risk of synchronous advanced neoplasia and Cancer
Implicated as one of the possible cause for interval cancer development.

10. Cancer risk in SSA/P’s Danish databases (1977-2009)
2045 CRC cases and 8105 controls (79 cases and 142 controls had SSA/Ps)
The 10 year risk for CRC:
4.4%- SSA/P’s with dysplasia
4.5% -TSA’s
2.3% -Conventional adenomas.
Erichsen R, et al. Gastroenterology. 2015

11. Carcinoma pathways ? ? Normal Mucosa Adenomatous polyps Adenocarcinoma
Adenoma-Carcinoma pathway (70-80%)- APC/KRAS pathway ?
Normal Mucosa Hyperplastic polyps Sessile serrated polyps Carcinoma ?
Serrated pathway (20-30%)- BRAF/ CpG-island methylation pathway/loss of MLH1- expression and MSI-H phenotype

12. Surveillance guidelines
AJG guideline. Sep 2012

13. Risk Factors for POLYPS
Haque TR. Dig Dis Sci Dec

14. What causes colon cancer?

15. Risk factors of Colorectal Cancer
Modifiable
Non-modifiable

16. Modifiable risk factors
Obesity
Smoking
Alcohol
Diet

17. Obesity and Colon cancer
Pro-inflammatory phenotype
VAT- Visceral adipose tissue
CRC risk increases by 7%  with BMI increase of 2.4 units
5% increased risk of CRC for per inch of waist circumference
Obesity Reviews Volume 13, Issue 12, pages , 3 SEP 2012 DOI: /j X x

18. Smoking and Colon cancer
30+ years of smoking- The risk of colon cancer is approximately doubled.
20+ years of smoking- Around three-fold increased risk of adenomatous polyps.
Giovannucci E et al: J Natl Cancer Inst. 1994 Feb

19. Alcohol and Colon cancer
Several studies suggest increased CRC (and other cancer) risk with alcohol consumption.
American Cancer Society: Alcohol limit
Men- 2 drinks per day.
Women- 1 drink per day.

20. Diet and Colon Cancer

21. Meat and Colon Cancer
2015
1907

22. Meat and Colon Cancer
World Health Organization (WHO) – Classified red meat as ‘carcinogen’ in their report in Oct 2015.
22 experts from 10 countries reviewed >800 studies.
18% increase CRC risk by consuming 50 grams of processed meat/day (about 4 strips of bacon or 1 hot dog/day).
For red meat, there was evidence of increased risk of colorectal, pancreatic, and prostate cancer.

23. Vegetarian diet and Colon cancer
Meta-analysis
9 studies- 686,629 individuals, 4062-colorectal cancer.
Vegetarian diet- did not decrease the risk of CRC.
Reduced risk of CRC:
Semi-vegetarian diet (meat >once/month but <once/week)
Pesco-vegetarian (fish consumption >once/month)
Godos J, et al. J Hum Nutr Diet 2016.

24. Vegetarian diet and Colon Cancer
Netherlands Cohort Study 
10,210 individuals (Vegetarians, Pescetarians, Meat eaters- 1 day/week, 2-5/week and 6-7/week)
20 years of follow-up- 437 CRC cases
Vegetarians, pescetarians, and 1 day/week meat eaters showed a non-significantly decreased risk of CRC compared to 6-7 day/week meat consumers.
The total NLCS study was initiated in September 1986 and includes 120,852 men and women aged 55–69 years at baseline.
Another study-JAMA. 2006 Feb 8;295(6):
Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.
Conclution- Veg diet did not decrease CRC.
Gilsing AM, et al. Sci Rep 2015.

25. Non-modifiable CRC risk factors
Age- Increase risk with aging (>50 years of age)
Personal history of colon adenomas
Family history of colon cancer or adenomas
Inflammatory bowel disease (Ulcerative colitis and Crohn’s colitis)
Diabetes
Race- African Americans have higher risk
Inherited/Familial syndromes

26. How can we prevent colon cancer?
Early detection and treatment

27. Early Detection Colonoscopy Stool tests- FOBT, FIT, Cologuard
Virtual colonoscopy- CT imaging

28. Force USPST. Screening for colorectal cancer: Us preventive services task force recommendation statement. JAMA 2016.

29. Who should get Screened?

30. US Preventive Services Task Force (USPSTF)
Force USPST. Screening for colorectal cancer: Us preventive services task force recommendation statement. JAMA 2016

31. Screening rates?
Year %
Utah - 70%

32. Cancer Facts and Statistics- Cancer.org

33. From- http://fightcolorectalcancer.org/

34. 277,000 new cases of Colon cancer 203,000 deaths from Colon cancer
Within next 20 years (2013 to 2030): Increasing screening rates to 80% by 2018 would prevent:
277,000 new cases of Colon cancer
203,000 deaths from Colon cancer
Meester RGS et al. Public health impact of achieving 80% colorectal cancer screening rates in the United States by Cancer 2015;121:

35. Utah Steering committee ‘80% by 2018’

36. Utah Steering committee ‘80% by 2018’

37. Utah Steering committee ‘80% by 2018’

38. Hereditary Colorectal cancer
Sporadic - 70%
Hamartomatous
polyposis <1%
Familial-25%
FAP <1%
Lynch syndrome: 1-3%
Burt. Gastroenterology 2010

39. Hereditary Colon Cancer
Familial Adenomatous Polyposis (FAP)
Lynch Syndrome
Serrated polyposis syndrome (SPS)
MUTYH polyposis
Hamartomatous polyposis

40. Familial Adenomatous Polyposis
Syndrome- APC gene mutation and subjects present with multiple polyps (>100).
Lifetime CRC risk- 100%, average age of CRC diagnosis is 39.
Other cancers-Duodenal, Thyroid, Desmoid, Osteomas etc

41. Colon polyps Colon polyps Duodenal Polyps Ampullary lesion
Add duodenal polyp pic
Duodenal Polyps
Ampullary lesion

42. Desmoid tumor

43. FAP- Surveillance/Management
CRC screening - Annual colonoscopy - Begins at Puberty.
Post surgical (colectomy or pouch)- Annual Ileal pouch or rectum surveillance.
Ileostomy- Surveil every 2 years.
Tx- Colectomy-cancer, high polyp burden

44. FAP- Surveillance Gastric/duodenal cancers- EGD starting age 25-30.
Fundic gland polyps- High grade dysplasia or cancer- surgery.
Thyroid cancer surveillance- Consider annual Ultrasound

45. Is there a medication to regress duodenal polyps in FAP?
a) True
b) False

46. Prevention measures Sulindac- Colon polyps, Rectal surveillance.
No other NSAID’s- Celecoxib was used but has cardiovascular risks.
Newer medications for duodenal polyp regression- University Of Utah study- promising early results (Erlotinib).

47. Lynch Syndrome
Inherited syndrome- Mismatch repair (MMR) genes defect (MLH1,MSH2,MSH6,PMS2).
Cancer risk- Colon*, Endometrium*, Stomach, Ovarian, Hepatobiliary, Upper urinary tract, Pancreatic, Small bowel and CNS.
2-4% of all colon cancers, Prevalence 1:440.
Lifetime CRC risk %.
Amsterdam Criteria (3-2-1 criteria) or Revised Bethesda criteria are used to recognize potential Lynch families.
The Amsterdam criteria can be remembered by the "3-2-1 rule" (3 affected members, 2 generations, 1 under age 50)
Revised Bethesda:
Below are the Revised Bethesda Guidelines for testing colorectal tumors for microsatellite instability (MSI).
Colorectal or uterine cancer diagnosed in a patient how is less than 50 years of age
Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumors, * regardless of age.
Colorectal cancer with the MSI-H ** histology *** diagnosed in a patient who is less than 60 years of age. +
Colorectal cancer diagnosed in one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed under age 50 years.
Colorectal cancer diagnosed in two or more first- or second-degree relatives with HNPCC-related tumors, regardless of age.

48. Lynch Syndrome-Surveillance
Colorectal cancer screening (50-80% risk)
Start colonoscopy by age of (MLH1,MSH2).
MSH6,PMS2 carriers-may start unless family h/o early onset cancer.
Screen every 1 to 2 years- confirmed mutation carriers.

49. Lynch syndrome- Surveillance
Endometrial cancer screening (40-60% risk)
- Prophylactic hysterectomy and b/l FT and ovary removal at age in carriers.
Endometrial biopsy and Transvaginal US annually in carriers or at risk patients.
Start age

50. Daily use of aspirin is recommended for colon cancer prevention in patients with Lynch syndrome?
True
b) False

51. Serrated Polyposis Syndrome (SPS)
Extreme phenotype
WHO criteria:
1) ≥ 5 serrated polyps proximal to sigmoid colon with 2 or more > 10 mm
2) Or Any number of serrated polyps proximal to sigmoid colon in subject with FDR with SPS
3) Or > 20 serrated polyps of any size distributed throughout colon

52. Serrated Polyposis Syndrome (SPS)
Increased Colorectal risk (25%–42%-our study at HCI-16%1)
Prevalence- 1:1272 (Spanish cohort), 1:2382 (Dutch cohort)
Smoking has an association
Clinical diagnosis
?Underlying genetic basis is not known
FDR need to be screened.
Jasperson K, Kanth P, Burt R et al. Dis Colon Rectum. 2013
IJspeert JEG, et al. Gut 2016.

53. Serrated Polyposis Syndrome (SPS)
Multiple adenomas- Should be tested for MUTYH polyposis- Referral for genetic counselling.
No defined extra-colonic cancer association. Only one study indicates possible risk of Pancreatic cancer.
NCCN recommend surveillance colonoscopy every 1-3 years.

54. Hamartomatous syndromeS
Peutz-Jeghers (STK11)
Juvenile polyposis (SMAD4 and BMPR1A)
PTEN-hamartoma tumor syndrome-Cowden, Bannayan–Riley–Ruvalcaba syndrome

55. When to refer for Genetic counseling/TEST?
Multiple family members with cancer, especially <50 year old (looks for colon, endometrial, ovarian etc)- Think Lynch..(Amsterdam/Bethesda criteria)
>/= 3 relatives with CRC.
>20 adenomas on colonoscopy.
h/o CRC and >10 adenomas on colonoscopy.
Strong FAP like phenotype on endoscopy.
FH of hereditary cancer syndromes.
Any young patient with colorectal cancer (age<50).
Any patient with SPS or multiple hamartomatous polyps.

56. summary
Colon cancer remains a significant health burden with high mortality and morbidity.
Early detection and treatment can prevent this potentially fatal disease.
Awareness of screening modalities for early detection in general population.
Understanding the risk factors and intervention in prevention of CRC.
Recognition of patients and families with potential hereditary cancer syndromes and use of genetic counseling for such population.

57. Thank you