New colon cancer and polyposis genes recently identified include NTHL1, POLE, POLD1, MSH3, and RNF43. Previous studies suggest these genes raise the risk for colon cancer and polyposis; however, recent data suggest that environmental factors may also play an important role in risk. Ultimately, these genes account for a very small fraction of polyposis cases.

For more information check out https://www.ncbi.nlm.nih.gov/pubmed/31243857 and https://www.ncbi.nlm.nih.gov/pubmed/31227763

In a study of 51 individuals with multiple colon polyps drawn from 48 families, genetic testing through whole-exome sequencing identified 7 individuals (from 3 unrelated families) to have a mutation in both copies of their NTHL1 gene, and pedigree structure was consistent with autosomal recessive inheritance.1 All these individuals had colorectal cancer and a large number of adenomas (ranging from 8-50), and none of the 8 cancers or adenomas tested showed microsatellite instability. There were also individuals who developed endometrial and duodenal cancer. A subsequent study of over 2400 families confirmed the association between this gene and colorectal cancer risk.²

¹Weren RD, et al. Nat Genet. 2015 Jun. PMID: 25938944.
²Broderick P, et al. Gastroenterology. 2017 Jan. PMID: 27713038.

For Individuals with Lynch Syndrome:

• Surveillance for gastric and small bowel cancer now indicates there is no clear data to support this, but surveillance can be performed every 3-5 years starting at age 40
• Lack of evidence to make a recommendation for pancreatic or prostate cancer screening, beyond those already recommended through other NCCN Guideline panels
• Increased breast cancer risk was acknowledged, however there is not enough evidence to support increased screening above what is recommended for the general population

In the multi-gene testing section:

• New genes added for colorectal cancer risk included NTHL1 and MSH3 (‘biallelic’ mutations)
• Indicated lack of data to determine screening recommendations among those with single (heterozygous) mutation in MUTYH and a second degree relative with colorectal cancer

For the complete updated versions of the NCCN Guidelines, please visit NCCN.org