Genetic Counseling for Hereditary Gastric and Pancreatic Cancer in High-Risk Gastrointestinal Cancer Clinics: An Effective Strategy.

Joan Llach,Leticia Moreira,Gerhard Jung,Francesc Balaguer,Mireia Díaz,Rebeca Moreira,Cristina Herrera-Pariente,Liseth Rivero-Sánchez,Antoni Castells,Miriam Cuatrecasas,Sabela Carballal,Ariadna Sánchez,Lorena Moreno,Teresa Ocaña,Maria Pellisé

doi:10.3390/cancers12092386

Abstract

The identification of high-risk groups of gastric (GC) and pancreatic adenocarcinoma (PC) due to a hereditary basis could imply a benefit in the affected families by establishing personalized preventive strategies. We aimed at assessing the diagnostic yield of GC/PC hereditary syndromes in individuals evaluated based on specific clinical criteria. In total, 77 unrelated individuals (45 from GC group/32 from PC group) were recruited: 51 (66.2%) cancer diagnosis ≤60 years, 3 (4%) with personal history of GC/PC and other cancer and 23 (29.8%) due to family history. Immunohistochemical analysis of DNA mismatch repair proteins was performed in 38 (49.3%) available tumors, being pathological in one (2%) GC. A genetic analysis was performed if clinical criteria of hereditary syndrome were fulfilled, identifying a mutation in 10/22 (45.5%) families [7/16 (43.7%) with GC and 3/6 (50%) with PC] and 19 (24.7%) fulfilled criteria of familial cancer. Diagnosis of cancer <40 years and personal history of other cancers were independent risk factors of a hereditary syndrome [OR:11.3 (95%IC 1.9–67); p = 0.007 and OR:17.4 (95% IC 2.5–119.9); p = 0.004; respectively]. The selection of patients based on clinical criteria leads to high diagnostic yield, detecting a causative germline mutation in almost half of the cases; therefore, both meticulous genetic counseling and use of multi-gen panels is crucial.

Highlights

IntroductionFamilial aggregation and hereditary component in cases of extra-colonic gastrointestinal tumors, such as gastric adenocarcinoma (GC) and pancreatic ductal adenocarcinoma (PC), have been less studied
Genetic counseling in the setting of gastrointestinal malignancies has been focused on the identification of hereditary colorectal cancer, and in Lynch Syndrome, the most frequent inherited form of colon cancer [1,2,3].familial aggregation and hereditary component in cases of extra-colonic gastrointestinal tumors, such as gastric adenocarcinoma (GC) and pancreatic ductal adenocarcinoma (PC), have been less studied
In depth personal and family oncological history in cases of GC or pancreatic adenocarcinoma (PC) is unusual, which implies that many tumors that could have a hereditary component or family aggregation are misclassified as sporadic, and, specific preventive measures are not applied to family members [10]

Summary

Introduction

Familial aggregation and hereditary component in cases of extra-colonic gastrointestinal tumors, such as gastric adenocarcinoma (GC) and pancreatic ductal adenocarcinoma (PC), have been less studied. These tumors represent a relevant health problem in developed countries due to their. Familial GC (FGC) is defined as ≥3 first- or second-degree relatives (FDR and SDR, respectively) with GC or ≥2 FDR/SDR with GC (at least one diagnosed

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