NEW YORK (Reuters Health) - Women with higher-risk variants of genes involved in estrogen metabolism have a greater risk of breast cancer, and greater estrogen exposure increases this risk, Taiwanese researchers report.
“These results provide support for the idea that increased estrogen exposure confers a higher risk of breast cancer by causing DNA damage,” Dr. Ting-Chih Cheng of the Institute of Biomedical Sciences in Taipei and colleagues write in the January 20th issue of the International Journal of Cancer.
The association between estrogen exposure and breast cancer risk is well known, Dr. Ching and his team note, with the “simple explanation” being that the hormone causes proliferation of breast epithelium, promoting tumor cell growth. But new evidence suggests that estrogen may also be involved in tumor initiation, specifically via oxidative metabolism of catechol estrogen (CE).
To investigate, Dr. Ching and colleagues examined risks associated with six genes involved in protecting against CE metabolism’s potentially harmful effects, comparing 469 patients with breast cancer to 740 healthy controls.
A trend for increased risk was seen with all of the higher-risk genotypes, but was only significant for catechol-O-methyltransferase (COMT), which detoxifies CE by methylation. The researchers found that greater estrogen exposure strengthened the relationship between high-risk genes and breast cancer.
In a previous study, the researchers identified a link between high-risk versions of genes involved in DNA double strand break (DSB) repair and breast cancer susceptibility.
In the current study, they found a joint effect for genes involved in one of two pathways involved in DSB repair -- the homologous recombination pathway -- and high-risk CE-metabolization genes on breast cancer risk.
“The findings of the present study and our recent identification of breast cancer risk associated with DSB repair genes could potentially have important impact on the prediction of breast cancer risk,” the researchers conclude. “These findings may result in significant improvements in the efficacy of population-based programs for the prevention of, and intervention for, breast cancer.”
Source: Int J Cancer 2005;113:343-353. [ Google search on this article ]
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