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Defining Phenotypes and Cancer Risk in Hyperplastic Polyposis Syndrome

Kalady, Matthew F. M.D.1,2; Jarrar, Awad M.B.B.S.1,2; Leach, Brandie M.S.2,3; LaGuardia, Lisa B.S.N.1,2; O'Malley, Margaret B.S.1,2; Eng, Charis M.D., Ph.D.2,3; Church, James M. M.B.Ch.B.1,2

Diseases of the Colon & Rectum: February 2011 - Volume 54 - Issue 2 - p 164-170
doi: 10.1007/DCR.0b013e3181fd4c15
Original Contribution

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.

1 Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio

2 Sanford R. Weiss, MD Center for Hereditary Colorectal Neoplasia, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio

3 Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio

Funding/Support: Dr Eng is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine, received a Doris Duke Distinguished Clinical Scientist Award, and is an ACS Clinical Research Professor, supported, in part, by the F.M. Kirby Foundation.

Presented at the meeting of The American Society of Colon and Rectal Surgeons, Minneapolis, MN, May 15 to 19, 2010.

Correspondence: Matthew F. Kalady, M.D., Assistant Professor of Surgery, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Department of Colorectal Surgery, Sanford R.Weiss, MD Center for Hereditary Colorectal Neoplasia, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Ave., A30, Cleveland, OH 44195. E-mail:

© The ASCRS 2011