Kocabaş Neslihan Aygün, Sardaş Semra, Cholerton Suzanne, Daly Ann K, Karakaya Ali Esat
Department of Toxicology, Pharmacy Faculty, Gazi University, 06330 Hipodrom, Ankara, Turkey.
Arch Toxicol. 2002 Nov;76(11):643-9. doi: 10.1007/s00204-002-0387-x. Epub 2002 Aug 21.
Epidemiological studies indicate that most risk factors for breast cancer are related to reproductive and hormonal factors. Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). Because of the important role of cytochrome P450 1B1 ( CYP1B1) and catechol O-methyltransferase ( COMT) in mammary estrogen and carcinogen metabolism, we examined the CYP1B1 and COMT genes to determine whether genetic variations could account for inter-individual differences in breast cancer. In this case-control study, we determined CYP1B1 and COMT genotypes in 84 breast cancer patients and 103 healthy unrelated women controls from a Turkish population. In the case of CYP1B1, we genotyped CYP1B13 (L432 V) allele. We found that carriers of the CYP1B13 allele were more frequent among breast cancer patients with adjusted odds ratio (OR) for age, age at menarche, age at first full-term pregnancy, body mass index (BMI) and smoking status of 2.32 (95% confidence interval 1.26-4.25) associated with the allele. However, this allele appeared to be a significant factor for susceptibility only in patients with a BMI greater than 24 kg/m(2). Menopausal status did not appear to affect susceptibility. In the case of COMT, there was no significant difference in susceptibility for breast cancer development between patients with low activity COMT-L (V158 M) allele and high activity COMT-H allele, and susceptibility was not affected by menopausal status, BMI or CYP1B1 genotype. We conclude that the CYP1B1* 3 allele appears to be a factor for susceptibility to breast cancer in Turkish women especially those with a BMI greater than 24 kg/m(2).
流行病学研究表明，大多数乳腺癌风险因素与生殖和激素因素有关。有人提出雌激素通过一种涉及其代谢产物儿茶酚雌激素（CE）的启动机制引发乳腺癌发展。由于细胞色素P450 1B1（CYP1B1）和儿茶酚-O-甲基转移酶（COMT）在乳腺雌激素和致癌物代谢中起重要作用，我们检测了CYP1B1和COMT基因，以确定基因变异是否可解释乳腺癌个体间差异。在这项病例对照研究中，我们确定了来自土耳其人群的84例乳腺癌患者和103名健康无关女性对照的CYP1B1和COMT基因型。对于CYP1B1，我们对CYP1B13（L432V）等位基因进行了基因分型。我们发现，在乳腺癌患者中，CYP1B13等位基因携带者更为常见，在调整了年龄、初潮年龄、首次足月妊娠年龄、体重指数（BMI）和吸烟状况后，该等位基因的优势比（OR）为2.32（95%置信区间1.26 - 4.25）。然而，该等位基因似乎仅在BMI大于24 kg/m²的患者中是易感性的重要因素。绝经状态似乎不影响易感性。对于COMT，低活性COMT-L（V158M）等位基因患者和高活性COMT-H等位基因患者在乳腺癌发生易感性方面无显著差异，且易感性不受绝经状态、BMI或CYP1B1基因型影响。我们得出结论，CYP1B1*3等位基因似乎是土耳其女性尤其是BMI大于24 kg/m²的女性患乳腺癌易感性的一个因素。
