TY - JOUR
T1 - 655Val and 1170Pro ERBB2 SNPs in familial breast cancer risk and BRCA1 alterations
AU - Tommasi, Stefania
AU - Fedele, Vita
AU - Lacalamita, Rosanna
AU - Bruno, Michele
AU - Schittulli, Francesco
AU - Ginzinger, David
AU - Scott, Gery
AU - Eppenberger-Castori, Serenella
AU - Calistri, Daniele
AU - Casadei, Silvia
AU - Seymour, Ian
AU - Longo, Salvatore
AU - Giannelli, Gianluigi
AU - Pilato, Brunella
AU - Simone, Giovanni
AU - Benz, Christopher C.
AU - Paradiso, Angelo
PY - 2007
Y1 - 2007
N2 - 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 investigate different gene SNPs association for risk defining.
AB - 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 investigate different gene SNPs association for risk defining.
KW - Breast cancer
KW - ERBB2
KW - Familiarity
KW - Risk
KW - Single nucleotide polymorphism
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M3 - Article
C2 - 17452776
AN - SCOPUS:34249775505
VL - 29
SP - 241
EP - 248
JO - Cellular oncology (Dordrecht)
JF - Cellular oncology (Dordrecht)
SN - 2211-3428
IS - 3
ER -