Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2016; 8(6): 509-519
Published online Jun 15, 2016. doi: 10.4251/wjgo.v8.i6.509
Genetic risks and familial associations of small bowel carcinoma
Santosh Shenoy
Santosh Shenoy, Department of Surgery, KCVA, University of Missouri at Kansas City, Kansas, MO 64128, United States
Author contributions: Shenoy S collected the data, wrote, and revised the manuscript.
Conflict-of-interest statement: There is no conflict of interest, no funding or financial disclosures.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Santosh Shenoy, MD, FACS, Department of Surgery, KCVA, University of Missouri at Kansas City, 4801 E Linwood Blvd, Kansas, MO 64128, United States. shenoy2009@hotmail.com
Telephone: +1-816-8614700-55431 Fax: +1-816-9224609
Received: December 23, 2015
Peer-review started: December 24, 2015
First decision: January 30, 2016
Revised: February 2, 2016
Accepted: March 14, 2016
Article in press: March 16, 2016
Published online: June 15, 2016
Abstract

Adenocarcinoma of small intestines (SBA) is a relatively rare malignancy with poor outcomes due to delayed diagnosis. Fifty percent of patients have metastases on presentation and therefore early detection and treatment offers the best long term outcomes. Certain genetic polyposis syndromes and familial diseases are associated with increased risks for SBA. These include familial adenomatous polyposis (FAP), Lynch syndromes (LS), Juvenile polyposis syndrome, Peutz-Jeghers syndrome, Crohn’s disease (CD) and celiac disease. Mutations in APC gene, Mismatch repair genes, STK11 gene, and SMAD4 gene have been implicated for the genetic diseases respectively. While there are no specific inherited genetic mutations for CD, genome-wide association studies have established over 140 loci associated with CD. CpG island mutations with defects in mismatch repair genes have been identified in celiac disease. Significant diagnostic advances have occurred in the past decade and intuitively, it would seem beneficial to use these advanced modalities for surveillance of these patients. At present it is debatable and no clear data exists to support this approach except for established guidelines to diagnose duodenal polyps in FAP, and LS. Here we discuss the genetic alterations, cancer risks, signaling mechanisms and briefly touch the surveillance modalities available for these genetic and clinical syndromes. English language articles from PubMed/Medline and Embase was searched were collected using the phrases “small-bowel adenocarcinoma, genetics, surveillance, familial adenomatous polyposis, lynch syndromes, Peutz-Jeghers syndrome, juvenile polyposis syndrome, CD and celiac disease”. Figures, tables and schematic diagram to illustrate pathways are included in the review.

Keywords: Small intestinal adenocarcinoma, Genetic risks, Mutations, Signaling pathways, Surveillance

Core tip: Adenocarcinoma of small intestine (SBA) is a relatively rare malignancy with poor outcomes due to delayed diagnosis. Certain genetic and familial diseases are associated with increased risks for SBA. These include Familial adenomatous polyposis, lynch syndromes, juvenile polyposis syndrome, Peutz-Jeghers syndrome, Crohn’s disease and celiac disease. We discuss the clinical implications of this aggressive cancer focusing on the genetic and familial associations, signaling mechanisms and available diagnostic modalities for surveillance.