Mutational analysis of the estrogen receptor-alpha gene in familial ovarian cancer.
OBJECTIVE
The genetic region of 6q25 containing the estrogen receptor-alpha (ER-alpha) gene is lost in a significant number of ovarian tumors. The aim of this study was to identify how inherited variation in the ER-alpha gene contributes to susceptibility to familial ovarian cancer.


METHODS
DNA obtained from 18 cases of familial ovarian cancer without mutation of the BRCA1 and BRCA2 genes, 20 cases with BRCA1 mutation, 20 cases of sporadic ovarian cancer, and 19 controls were screened for mutations in the coding region of the ER-alpha gene using direct sequencing.


RESULTS
Two germline missense variants at codons 307 [GCC(Ala)-->TCC(Ser)] and 347 [ACC(Thr)-->TCC(Ser)] were detected in two unrelated cases with BRCA1 mutation, but not in all other cases tested. Three polymorphisms in codon 10 [TCT-->TCC(Ser)], codon 325 [CCC-->CCG(Pro)], and codon 594 [ACA-->ACG(Thr)] were identified in this series, and a higher frequency of the allele TCC at codon 10 and a lower frequency of the allele CCG at codon 325 were observed in familial cases without BRCA1 mutation, compared with those in familial cases with BRCA1 mutation, in both the sporadic cases and in the controls.


CONCLUSIONS
We could not detect pathogenic mutations of the ER-alpha gene in ovarian cancer cases without BRCA1 mutation. However, association analyses of two polymorphisms suggest that the ER-alpha gene or a gene located close to the ER-alpha locus might be related to susceptibility of familial ovarian cancer without BRCA1 mutation.
Wu
Hong-Jun
HJ
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Sekine
Masayuki
M
Kashima
Katsunori
K
Hirai
Yasuo
Y
Hatae
Masayuki
M
Kobayashi
Iwao
I
Obata
Koshiro
K
Enomoto
Takayuki
T
Umesaki
Naohiko
N
Ushijima
Kimio
K
Tanaka
Kenichi
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic
D004273:DNA, Neoplasm; D047628:Estrogen Receptor alpha