title: Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer.
abstract: Ovarian steroids are one of the strongest risk factors for breast cancer. Sex hormone-binding globulin (SHBG) binds and transports sex steroids in the blood, regulating their bioavailable fraction and access to target cells. It can also inhibit the estradiol-induced proliferation of breast cancer cells through its membrane receptor. Three coding-region polymorphisms, which lead to an amino acid change, have been reported. We studied the influence of these three polymorphisms on breast cancer risk in three different populations: Polish familial breast cancer cases, 27% of them carrying a BRCA1/BRCA2 mutation, Nordic familial and sporadic breast cancer cases. The reported G to A polymorphism in exon 1 was not found in the 423 analyzed samples. Instead, we found a C to T transition causing an arg to cys amino acid change within the same codon in one Polish breast cancer patient and her daughter. Both of them were heterozygotes for the exon 8 G to A polymorphism as well. They were diagnosed for bilateral breast cancer and carried a BRCA1 mutation (5382insC). Analysis of the tumor samples showed that they had lost the wild-type allele both at exons 1 and 8 of the SHBG gene. Analysis of the other Polish samples showed no correlation of the exon 8 polymorphism to breast cancer, bilateral breast cancer, BRCA1/BRCA2 mutations or age at diagnosis. No association of the exon 8 polymorphism with breast cancer in the Nordic familial or sporadic cases was found. The C to T polymorphism located in exon 4 was rare in all the studied populations (overall allele frequency 0.011). However, in each of the study populations there was a trend for a lower variant allele frequency in cancer cases than in controls. Variant allele frequency in all the breast cancer cases was significantly lower than in all the controls (chi(2) = 5.27, P-value 0.02; odds ratio = 0.23, 95% confidence interval 0.05-0.84).
authors.affiliation: Department of Biosciences at Novum, Karolinska Institute, SE-14157 Huddinge, Sweden. asta.forsti@cnt.ki.se
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
authors.forename: Qianren
authors.initials: Q
authors.lastname: Jin
authors.forename: Ewa
authors.initials: E
authors.lastname: Grzybowska
authors.forename: Magnus
authors.initials: M
authors.lastname: Söderberg
authors.forename: Helena
authors.initials: H
authors.lastname: Zientek
authors.forename: Marzena
authors.initials: M
authors.lastname: Sieminska
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Rogozinska-Szczepka
authors.forename: Ewa
authors.initials: E
authors.lastname: Chmielik
authors.forename: Beata
authors.initials: B
authors.lastname: Utracka-Hutka
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D000328:Adult; D000368:Aged; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D011956:Receptors, Cell Surface; D012738:Sex Hormone-Binding Globulin; C063572:sex hormone-binding globulin receptor