title: Low penetrance alleles as risk modifiers in familial and sporadic breast cancer.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, Escuela de Enfermería 7ª, Hospital Universitario La Fe, Avenida Campanar 21, Valencia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Esteban Cardeñosa
authors.forename: Inmaculada
authors.initials: I
authors.lastname: de Juan Jiménez
authors.forename: Sarai
authors.initials: S
authors.lastname: Palanca Suela
authors.forename: Isabel
authors.initials: I
authors.lastname: Chirivella González
authors.forename: Angel
authors.initials: A
authors.lastname: Segura Huerta
authors.forename: Ana
authors.initials: A
authors.lastname: Santaballa Beltran
authors.forename: María
authors.initials: M
authors.lastname: Casals El Busto
authors.forename: Eva
authors.initials: E
authors.lastname: Barragán González
authors.forename: Oscar
authors.initials: O
authors.lastname: Fuster Lluch
authors.forename: José
authors.initials: J
authors.lastname: Bermúdez Edo
authors.forename: Pascual
authors.initials: P
authors.lastname: Bolufer Gilabert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000209:etiology*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D060045:Genes, Modifier / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000209:etiology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D018797:Cell Cycle Proteins; C549605:HUS1 protein, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D004247:DNA; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; C505530:CASP8 protein, human; D053181:Caspase 8