544P - Leucine-Rich and Immunoglobulin-Like Domains Germline Polymorphisms Predict Clinical outcome in Metastatic Colorectal Cancer

Abstract

ABSTRACT Background Leucine-rich and immunoglobulin-like domains (LRIG) 1, 2, and 3 are integral membrane proteins recently discovered as regulators of the epidermal growth factor (EGF) signalling. LRIG1 negatively regulates growth factor signaling and increasing evidence indicates that LRIG1 is a tumor suppressor in certain cancer types. Lrig1 is expressed at low levels in several cancer types but is overexpressed in some colorectal tumors. We postulate that polymorphisms located in the LRIG1 gene could influence the EGFR signalling pathway and be related with the clinical outcome in metastatic colorectal cancer (mCRC). Methods We studied 126 mCRC treated with a first-line oxaliplatin/5-fluorouracil chemotherapeutic regimen. Common and putatively functional polymorphisms in the LRIG gene were selected using public literature resources and databases (NCBI, PubMed, db SNP, Ensembl and GeneCards Version 3). These germline polymorphisms were analyzed using a Fluidigm equipment in DNA samples extracted from peripheral blood. Overall survival (OS) was evaluated according to each genotype. Results Two non-synonymous (c3158A > C and c1843A > G) and two synonymous (c2221T > C and c1317C > T) common and putatively functional polymorphisms in the LRIG1 gene were selected. There were significant associations between LRIG1 c1317C > T and c3158A > C polymorphisms and clinical outcome. OS was lower for patients harboring a T/T genotype than for patients with the C/C or C/T genotypes (p= 0.01). In the case of the c3158A > C polymorphism, patients harboring a C/C genotype had a lower OS than patients with an A/A or A/C genotypes (p = 0.047). Conclusions In this study, we identified common germline variants in LRIG1 gene predicting clinical outcome in patients with mCRC receiving first-line oxaliplatin-based chemotherapy. Disclosure All authors have declared no conflicts of interest.