Defining phenotypes and cancer risk in hyperplastic polyposis syndrome

Dis Colon Rectum. 2011 Feb;54(2):164-70. doi: 10.1007/DCR.0b013e3181fd4c15.


Background: Hyperplastic polyposis syndrome is a rare syndrome of colorectal cancer predisposition. Patterns of inheritance of hyperplastic polyposis syndrome are not obvious and the clinical definition is relatively arbitrary. We hypothesize that there are multiple phenotypes included in what is currently called hyperplastic polyposis syndrome. We performed this review of a large series of patients who presented with multiple serrated polyps to look for clinical patterns that may confirm our hypothesis.

Methods: Hereditary colorectal cancer, colonoscopy, and clinical databases from a single institution were queried for patients meeting the following criteria: 1) ≥ 20 serrated colorectal polyps; 2) ≥ 5 serrated polyps proximal to the sigmoid; 3) ≥ 2 serrated polyps ≥ 10 mm in size; 4) any serrated polyps in a person with at least one first-degree relative who has hyperplastic polyposis syndrome. Records were reviewed for demographics, polyp details, and personal or family history of colorectal extracolonic malignancy.

Results: One-hundred fifteen patients were included. Median age at diagnosis was 62 years and 56% were male. Ninety-seven percent were white. Twenty-five percent of patients had a personal history and 38% had a family history of colorectal cancer. Twenty-eight percent of patients had a personal history and 54% had a family history of extracolonic cancer. Phenotype analysis identified 3 patterns: relatively few large, right-sided polyps (n = 55), many small left-sided polyps (n = 18), and a combination of both left- and right-sided polyps (n = 42). The right-sided phenotype had more sessile serrated polyps and tended to develop colorectal cancer at a younger age.

Conclusions: There are at least 3 different but overlapping clinical phenotypes within hyperplastic polyposis. Recognizing this clinical heterogeneity is important in defining underlying genetic causes.

MeSH terms

  • Adenoma / genetics
  • Adenoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Intestinal Polyposis / genetics*
  • Intestinal Polyposis / pathology
  • Male
  • Middle Aged
  • Neoplasms / genetics
  • Phenotype
  • Precancerous Conditions / genetics