Surprising Genetic Mutations in Polyposis Study

A recent cross-sectional study (PP Stanich et al. Clin Gastroenterol Hepatol 2019; 17: 2008-15, editorial 1942-44) identified a high frequency of genetic mutations among adults with at least 10 colonic polyps (cumulative burden of either adenomatous or hamartomatous).

This study had 3789 subjects who underwent multigene panel testing (MGPT) from 2012-16.

  • All subjects had at least 14 CRC-associated genes tested: APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, TP53
  • A subset had 3 more newly recognized polyposis genes: GREM1, POLD1, and POLE

Key findings:

  • A mutation in at least 1 gene was found in 13.7%
  • In those with fewer than 20 cumulative adenomas, 7.6% had a disease-associated genetic mutation with the majority (5.3%) being nonpolyposis CRC genes
  • Younger patients, 18-29, were more likely to have mutations in any gene.  For example, among patients with 10-19 polyps, these younger patients had a mutation in one of these genes in 27.8%; this is more than double the rate in any other age group.
  • Hamartomatous polyps, regardless of number, had a very high yield with genetic testing: 40% with 10-19 polyps and 72% with 20-99 polyps.

Limitations:

  • There is a referral bias in that the population was derived from a testing laboratory (Ambry)
  • In clinical practice, genetic testing frequently results in variants of unknown significance

My take: This study shows that genetic mutations are fairly frequent in patients with cumulative polyp burden of 10 or more, especially in younger age groups.  The surprising finding is the high frequency of nonpolyposis CRC genes.  Thus, in patients with adenomatous polyposis, testing beyond APC and MUTYH may be needed.

Related blog posts:

Atlanta Botanical Garden

World Congress 2016 Postgraduate Course

I’ve attached (with permission) the syllabus from the World Congress 2016 Postgraduate Course: 2016-world-congress-postgraduate-course-syllabus

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One lecture that I will highlight with a few slides is from Dr. Martin Martin (pg 53-62) which emphasizes a new model for evaluating neonatal intestinal failure/congenital diarrhea by using whole exome sequencing –see slides below.

Other pointers:

  • Pg 82.  Breastmilk associated with shorter duration of TPN dependence in short bowel syndrome
  • Pg 137. Look for vasculopathy (MRI/MRA) and renal disease in Alagille syndrome
  • Pg 152. Lactated ringer’s likely better in acute pancreatitis than normal saline.
  • Pg 171. If constipation at less than 1 year is untreated, >60% have issues with constipation at age 3.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.