Colorectal cancer risk in hamartomatous polyposis syndromes

Abstract

Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as "hamartomatous polyposis syndromes", "Peutz-Jeghers syndrome", "juvenile polyposis syndrome", "juvenile polyp", and "PTEN hamartoma tumour syndrome" (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented.

TGF-β Tumor Suppression through a Lethal EMT

“…Acting through membrane receptor kinases, TGF-β activates Smad2 and Smad3 transcription factors (TFs), which bind Smad4 as an essential partner for many, though not all TGF-β responses (Massagué, 2012). Germline mutations in Smad4 result in familial juvenile polyposis syndrome (Howe et al, 1998), which predisposes to adenocarcinomas of the colon, stomach, and pancreas (Campos et al, 2015). Somatic inactivation of TGF-β receptors and Smad proteins are frequent in gastrointestinal carcinomas, with Smad4 inactivation in nearly half of pancreatic ductal adenocarcinomas (PDA) (Hahn et al, 1996).…”

Hamartomatous Polyps and Associated Syndromes

“…To diagnose PJS, a patient must have two or more hamartomatous polyps in the gastrointestinal tract or have a family history of PJS with either one confirmed PJS polyp or typical perioral pigmentation. 6 PJS polyps are most prevalent in the small intestine (range, 70-95%) but may also be present in the large intestine (range, 24-50%) and stomach (25%). Polyps typically develop around the time of early adolescence.…”

“…5 A third hypothesis is based on the idea that hamartomatous polyps may develop foci of adenomas, which then can proceed to malignant degeneration. 6 Most hamartomatous polyps of the colon and rectum, occur in the setting of an inherited syndrome, but they can also be sporadic. In the pediatric population, solitary juvenile hamartomatous polyps are the most common type encountered during colonoscopy (70.5% of polyps found).…”

Hamartomatous Tumors in the Gastrointestinal Tract

“…Its histological diagnosis is difficult. The penetrance of JP is incomplete and heterogeneous, with a family history present only in 20-50% of cases [9] .…”

“…It also allows reduction of the risk of surgery and subsequent short bowel syndrome. Accordingly, some authors propose endoscopic resection of all polyps >15 mm, even in asymptomatic patients [9] .…”