Phenotypic diversity in patients with multiple serrated polyps: a genetics clinic study

Abstract

ObjectiveHyperplastic polyposis is a colonic polyposis condition of unknown aetiology. The purpose of this study was to examine the spectrum of phenotypic variation in patients with multiple serrated polyps as a basis for gene discovery.MethodsOne hundred and twenty-six patients with multiple (≥5) serrated polyps were recruited to the study. Polyp counts were extracted from histology and colonoscopy reports. Ethnicity was self-reported. Family history of cancer data were derived from pedigrees. Ascertainment status was classified as either index case or identified by screening.ResultsThe average reported polyp count was 39. Patients with highest polyp numbers were more likely to be male (P = 0.02). Colorectal cancer (CRC) was identified in 49 of 119 patients (41%) and 28% of these patients had multiple CRC. Young onset patients had higher polyp numbers (P = 0.03) and were more likely to have their CRC in the distal colon (P = 0.02). CRC was significantly associated with the presence of adenomas (P = 0.03). Patients were divided into moderate polyposis (5-79 serrated polyps) and dense polyposis (80 or more) categories. The dense polyposis category was associated with a lack of family history for CRC (P = 0.034) and male gender (P = 0.014), independent of ascertainment status and recruitment site.ConclusionMultiple serrated polyps were associated with an increased personal risk of CRC. A subset of patients with the highest polyp numbers was more likely to be male and to have no family history of CRC. This result suggests heterogeneous modes of inheritance and has implications for studies investigating the genetic basis of multiple serrated polyps.

Phenotypic characterization and familial risk in hyperplastic polyposis syndrome

“…SSAs are considered the main precursor of CRC in HPS, its scarcity in our sample may explain the low number of CRC cases, in opposition to the works of Buchanan [24] or Lage et al [17] in which 40% of patients had CRC. Interestingly, in our single case of adenocarcinoma, the tumor was grafted in TA.…”

Type 1 serrated polyposis represents a predominantly female disease with a high prevalence of dysplastic serrated adenomas, without germline mutation in MUTYH, APC, and PTEN genes

“…3,9,10,15 In the three largest series published to date, 11 25% to 38% of serrated polyposis patients presented with at least one CRC, and multiple CRCs were common. 16 This relatively low rate of CRC in our study could be explained by the fact that partial or subtotal colectomy was performed in 51.7% of our patients. In our experience, despite the fact that a majority of our patients had at least partial colectomy, there is a significant place for endoscopic treatment in patients with sessile serrated polyposis.…”

“…18 On the contrary, Huang et al found no association between smoking and advanced serrated polyps. 19 Current smoking was associated with a significantly higher polyp number in patients with serrated polyposis, 16 and the prevalence of current smokers was higher among serrated polyposis patients than in the general population. 11,20 Our study confirms a high rate of tobacco users in type 1 serrated polyposis patients with 82.8% of smokers (a rate of 65.6% is usual in the literature): i.e.…”

Serrated polyps as precursor lesions of colorectal cancer: current status and future directions. Mini-review.

“…It became known that colon cancer can be the product of a mutation of several genes, each having sensitivity to environmental factors, such as smoking, physical inactivity, overweight and obesity, consumption of red meat and excessive alcohol consumption [6]. We know that with an increase in the life expectancy the risk of developing of CRC also increases, which is associated with an increased risk of CIMP-high BRAF-mutated CRC [7]. Recent data suggest that the probability of CRC is higher in family members of patients with BRAF-mutated CRC, than in patients without a family history [8].…”