Genetic susceptibility of catechol-O-methyltransferase polymorphism in Japanese patients with breast cancer.
Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens. It has been reported that COMT polymorphism is a representative genetic trait related to the susceptibility of an individual to breast cancer. However, there is no consensus concerning the association between breast cancer in Japanese patients and COMT polymorphism. To analyze the polymorphism distribution in Japanese patients with breast cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used. Based on an analysis of 201 Japanese patients with breast cancer and 352 healthy control subjects, a significant difference was observed in either the distribution of genotypes (p=0.03) or allele frequencies between the two groups (p=0.01). The relative risk of breast cancer for genotypes (COMT(Met/Met) and COMT(Val/Met)) including the variant allele (COMT(Met)) was 1.47 compared to the wild allele (COMT(Val)) and homozygote (COMT(Val/Val)). Furthermore, the distribution of genotypes in post-menopausal patients with breast cancer showed a significant difference with that of healthy subjects of the same menopausal status (p=0.01). No significant difference was found between the distribution of genotypes and clinicopathological features of the cancer. These results suggest that COMT polymorphism may thus be implicated as a genetic trait affecting the susceptibility of an individual to breast cancer in a Japanese population and be an important genetic risk factor in the development of breast cancer in post-menopausal women.
Inoue
Hiroshi
H
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan.
Shibuta
Kenji
K
Matsuyama
Ayumi
A
Yoshinaga
Keishi
K
Sadanaga
Noriaki
N
Ueo
Hiroaki
H
Barnard
Graham F
GF
Mori
Masaki
M
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007564:Japan; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017698:Postmenopause / Q000235:genetics; D017697:Premenopause / Q000235:genetics
D004273:DNA, Neoplasm; D002394:Catechol O-Methyltransferase; C048422:endodeoxyribonuclease NlaIII; D015252:Deoxyribonucleases, Type II Site-Specific