Both breast and
ovarian cancers are associated with HER2 receptor activation, which usually results from receptor overexpression and/or gene amplification. The HER-2 gene harbors a polymorphism at
codon 655 (GTC/
valine to ATC/
isoleucine) in the transmembrane domain region, which has been associated with an elevated risk of
breast cancer. The objective of this study was to determine whether the polymorphism is under a selection pressure during breast and ovarian
carcinogenesis. The
Ile/Val genotype was present in 41% (9/22) of the normal
DNA of
breast cancer patients. An allelic imbalance in the
tumor tissue was found in three
breast tumors, with overrepresentation of the Val allele. HER-2 was amplified and overexpressed in these
tumors. Half of the eight ovarian
tumor patients carried heterozygous
Ile/Val genotypes. In contrast to
breast tumors, all these
ovarian cancer specimens showed the presence of the Ile allele. In our selected set of
tumors, the Val allele was overrepresented in the subset of HER2-positive breast
cancers and the Ile allele in serous
ovarian cancer. Further analyses of
tumors with known gene amplifications and overexpression may reveal novel associations between germline polymorphisms and development of sporadic
tumors.