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Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer.
Carcinogenesis 2002: 23 (8) s.1315-1320, il., tab., bibliogr. 37 poz.
Hasła klasyfikacyjne GBL:
ginekologia i położnictwo
praca opublikowana za granicą
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 oead 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 p.c. 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 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 (overal allele frequency 0.011)...
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