Journal Article

Low penetrance alleles as risk modifiers in familial and sporadic breast cancer

Casals El Busto, María, Barragán González, Eva, Segura Huerta, Ángel, Esteban Cardeñosa, Eva, Fuster Lluch, Oscar, Bermúdez Edo, José, Bolufer Gilabert, Pascual, Santaballa Beltran, Ana, Chirivella González, Isabel, Palanca Suela, Sarai, de Juan Jiménez, Inmaculada

2012

Overview

The aim of the study is to investigate the relevance of rs1056663 and rs2708861 HUS1 polymorphisms, and rs104548, rs2981582 and rs2910164 polymorphisms of CASP8 , FGFR2 and micro RNA 146A genes, respectively, as risk modifiers in hereditary breast or ovarian cancer (BC/OC) and risk factors in sporadic BC. We performed a case–control study in 189 healthy controls (CG) and 538 BC/OC cases, 340 with familial history of BC/OC (130 carriers of BRCA1/2 mutations and 210 non-carriers) and 198 sporadic BC/OC. The polymorphisms were assessed by real-time PCR using primers and fluorescent-labelled hybridization probes. We found statistically significant differences between familial BC/OC and CG for rs1056663 and rs2708861 HSU1 polymorphisms and rs2981582 FGFR2 polymorphism, particularly in non-carriers of BRCA1/2 mutations. In this group we found statistical differences for rs1056663 HSU1 and rs2981582 FGFR2 polymorphisms ( p -trend < 0.006). The logistic regression confirmed that rs2981582 FGFR2 polymorphism (OR = 2.09; 95 % CI 1.35, 3.20) and the interaction between rs1056663 and rs2708861 HUS1 polymorphisms increased the risk of cancer (OR = 1.87; 95 % CI 1.19, 2.92). Furthermore, we found that the presence of rs1056663 and rs2708861 HUS1 polymorphisms is associated with early age of presentation of BC ( p  = 0.015) in the group of non-carriers of BRCA1/2 mutations. In addition, no association of the polymorphisms studied in sporadic BC was observed. In conclusion, the HUS1 and FGFR2 polymorphisms act as risk BC modifiers in familial BC/OC, particularly in the group of non-carriers of BRCA1/2 mutations.

• Publisher: Springer Netherlands,Springer Nature B.V
• Subject: Adult / Age / Aged / Aged, 80 and over / Biomedical and Life Sciences / Biomedicine / BRCA1 protein / BRCA1 Protein - genetics / BRCA2 Protein - genetics / Breast cancer / Breast Neoplasms - etiology / Cancer Research / Case-Control Studies / Caspase 8 - genetics / Cell Cycle Proteins - genetics / DNA - analysis / DNA - genetics / DNA probes / Epidemiology / Female / Fibroblast growth factor receptor 2 / Gene Frequency / Gene polymorphism / Genes, Modifier - genetics / Genetic Predisposition to Disease / Genetic Testing / Germ-Line Mutation - genetics / Human Genetics / Humans / Hus1 protein / MicroRNAs - genetics / Middle Aged / Mutation / Original Article / Ovarian cancer / Ovarian Neoplasms - etiology / Polymerase chain reaction / Polymorphism, Genetic - genetics / Primers / Prognosis / Real-Time Polymerase Chain Reaction / Receptor, Fibroblast Growth Factor, Type 2 - genetics / Risk Factors / RNA / Statistical analysis / Statistics