#29 Sessile Serrated Polyps: Not a Hereditary Syndrome!

Study #29

There has been a lot of time and money spent on trying to find a “gene” for serrated polyposis. It was obvious to me that this is an artificially invented “syndrome” with diagnostic criteria invented on the “back of an envelope”. I wanted to stop pointless research into finding a gene so that more time could be spent on looking at other risk factors.

Cauley CE, Hassab TH, Feinberg A, Church J. Sessile Serrated Polyposis: Not an Inherited Syndrome?. Dis Colon Rectum. 2020; 63: 183-189.

Background: Researchers are searching in vain for a coherent genetic explanation for serrated polyposis. We hypothesize that there is no consistent monogenetic inheritance.

Objective: The purpose of this study was to describe the serrated polyposis phenotype, assessing features of mendelian inheritance, and to compare these features with patients with a solitary sessile serrated lesion.

Design: This was a retrospective review of a prospectively maintained database comparing patients with serrated polyposis versus solitary sessile serrated lesions.

Settings: The study was conducted at a single-institution tertiary referral center.

Patients: Patients with serrated polyposis meeting World Health Organization criteria type I (≥5 serrated polyps proximal to the sigmoid, ≥2 of which are ≥10 mm in diameter) and isolated sessile serrated lesions were included MAIN OUTCOME MEASURES:: Disease phenotype was the main outcome measured.

Results: A total of 46 serrated polyposis patients were identified. Median age of first sessile serrated lesion was 66 years (interquartile range, 42-70 y). A total of 60.3% were current or past smokers (mean = 38.6 packs per year). Serrated polyposis patients had a higher number of all types of polyps (26.3 vs 4.4) and a higher rate of high-grade dysplasia (19.6% vs 3.7%) compared with patients with a solitary sessile serrated lesion. A total of 36.2% of patients had personal history of noncolorectal cancers, including skin, prostate, breast, thyroid, and renal cell cancers and leukemia. In addition, 32.6% had a family history of colorectal cancer in first- or second-degree relatives; these cancers were not young age of onset. Breast and prostate cancers were also common (family history of any cancer, 83.0%). Ten patients underwent genetic testing: 4 had negative panels, 1 had a pathogenic variant in MSH2, 1 an IVS7 deletion in PTEN, 2 negative APC sequencing (1 negative MYH), and 1 a pathogenic variant in Chek2.

Limitations: RNF4 was not sequenced. Genetic analysis was performed on a subset of patients.

Conclusions: The rate of associated cancers suggests an underlying genetic predisposition to disordered growth, but serrated polyposis does not have typical features of dominant inheritance.