IOS Press 655Val and 1170Pro ERBB2 SNPs in familial breast cancer risk and BRCA1 alterations

Abstract. Human ERBB2 presents several SNPs. One of these, Ile655Val, introduces a structural change in the transmembrane region of ERBB2 and has been the focus of debate over its potential role as a susceptibility marker for breast cancer risk. Another SNP, Ala1170Pro, introduces a structural change in the carboxyl-terminal regulatory domain of the protein, but its clinical and biological importance remains undefined. The aim of this study was to investigate the association of rare alleles of both SNPs and the risk of developing breast cancer, BRCA1 alterations and clinical-pathological features of Caucasian breast cancer patients with familial history of breast/ovarian cancer. The originality of the present paper is that it is the only specifically focusing on the relationship between ERBB2 SNPs and familiarity/BRCA1 characteristics. A consecutive series of 628 patients with first diagnosis of breast cancer and 169 healthy people had DNA analyzed for both SNPs. Genotypic or allelic frequencies of ERBB2 SNPs in breast cancer patients were similar than in controls. The variant allele 655Val was significantly associated with younger age (p = 0.009) particularly associated with patient family history of breast cancer (p = 0.02). The 655Val allele was also more commonly found in invasive, while the variant 1170Pro in estrogen receptor positive breast cancers. Furthermore, this last SNP seems to be strictly associated with the presence of BRCA1 polymorphisms. In conclusion, these findings point to the existence of an association of ERBB2 allelic variants at both loci with specific breast tumor phenotypes and to the need of deeply investigat