1997 Fiscal Year Final Research Report Summary
Polymorphisms of the estrogen receptor gene in familial breast cancer
| Project/Area Number |
08457311
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Nagoya City University |
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Principal Investigator |
KOBAYASHI Shunzo Nagoya City University Medical School, Department of Surgery II,Associated Professor, 医学部, 助教授 (50080057)
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| Co-Investigator(Kenkyū-buntansha) |
IWASE Hirotaka Nagoya City University Medical School, Department of Surgery II,Assistant Profes, 医学部, 講師 (40211065)
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| Project Period (FY) |
1996 – 1997
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| Keywords | familial breast cancer / estrogen receptor gene / mutation / polymorphism / ERbeta / methylation |
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| Research Abstract |
1)Possible linkage to the estrogen receptor gene
We demonstrated a possible linkage to the estrogen receptor (ER) gene in four Japanese breast cancer families, using three genetic markers (ESR,point variations of codon 10,325) in the ER gene and four markers (D17S250, D17S846, D17S855, D17S579) in the BRCA1 region. In two of the four families, the affected women shared allele type of the ER gene, but did not share BRCA1 allele types. Unfortunately, we could not find out any mutation of the ER gene in the families.
2)Estrogen receptor gene and breast cancer susceptibility
We previously found 2 types of sequence variants in exon 1 and exon 4, indicated two silent mutations in codon 10 (TCT to TCC) and codon 325 (CCC to CCG), respectively. Although the frequency of these polymorphic sites were not correlated with hormone receptor status and other clinico-pathologic factors, the variant in codon 325 tended to be seen more frequently in breast cancer patients than in non-cancer control cases (P=0.057). Since codon 325 is located in the hormone binding domain, this polymorphic site which appears to correlate with breast cancer susceptibility may affect ER function. Alternatively, this polymorphism may be in linkage disequilibrium with a coding or undetectable regulatory mutation.
3)Loss of hormone dependency and alterations of the ER gene
It is a substantial problem that hormone independence may occur during breast cancer treatment. However, genetic alterations of the ER gene, such as missense, nonsense mutations, could not affect the loss of ER function. DNA methylation frequently occurred in the patients with ER negative tumor. It has been suggested that the epigenetic changes, alternative splice variants and DNA methylation of the ER gene, may affect ER function. Additionally, a novel estrogen receptor, ERbeta, was recently cloned, so ERbeta may affect the classical ER (ER*) function. We will focus these area in the future.
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