兒茶酚氧位甲基轉移遺傳多形性為台灣乳癌致癌感受性因子

Abstract

Both epidemiologic and cell biology studies have documented the contribution of estrogen to the development of breast cancer. Well-established risk factors for breast cancer, including age at menarche, age at menopause, parity, and age at first full-term pregnancy (1, 2,3), are operative by way of hormonal mechanism. Hypotheses in which estrogen is involved in tumorigenesis are based on the general concept that cell division plays a crucial role in cancer development, and that reproductive factors that increase mitotic activity in the breast epithelium also increase cancer risk (4). On this basis, the role of reproductive hormones during tumorigenesis would be largely related to epigenetic alteration and tumor promotion. However, recent studies showed that estrogen metabolites can bind to DNA and trigger damage (5-7), suggesting that estrogen might be a complete carcinogen (8) that can directly cause genetic alteration and effect tumor initiation. This possibility is supported by the finding that women with reduced amounts of the enzymes responsible for removing reactive estrogen metabolites are at higher risk of developing breast cancer (9). To comprehensively elucidate the estrogen-initiating mechanism of tumorigenesis in breast cancer and to dissect the contribution of individual estrogenmetabolizing genes involved in this mechanism, this molecular epidemiologic study sought to determine if polymorphisms in the genes involved in estrogen biosynthesis (CYP17) and hydroxylation (CYP1A1) and inactivation of the reactive metabolites (COMT) may be associated with elevated risk of breast cancer, and if the association between genotypes and risk may be modified by estrogen exposure.