Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer
Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer
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DOI：
10.1007/s10549-006-9308-7
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发表时间：
2007-03-01
影响因子：
3.8
通讯作者：
Ahsan, Habibul
中科院分区：
文献类型：
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作者：
Greenlee, Heather;Chen, Yu;Ahsan, Habibul
我们研究了与雌激素代谢相关的基因多态性之间的关联（CYP 1B 1密码子432 G-> C rs#1056836，CYP 1B 1密码子453 A-> G rs#1800440，COMT密码子158 G-> A rs#4680）和生物合成（CYP 17 T -> C启动子rs#743572，CYP 19外显子4 TTTA重复）和尿雌激素代谢物（2-羟基雌激素（2-OHE），16 α-羟基雌酮（16 α-OHE 1），和他们的比例）在64个绝经前和绝经后妇女的乳腺癌家族史的初步研究。妇女参加了大都会纽约乳腺癌家庭登记处，这是国家癌症研究所乳腺癌家庭登记处的六个国际网站之一。我们使用线性回归来研究遗传变异对对数转换的尿雌激素代谢产物的影响。在调整绝经状态、BMI和年龄后，CYP 1B 1密码子453 G变异等位基因携带者的2-OHE水平降低31.0%（P值= 0.05），16 α-OHE 1水平降低40.2%（P = 0.01）。将分析限制在绝经前女性（n = 41）后，结果相似。与其他研究一致，在绝经前妇女中，COMT密码子158 A变异等位基因携带者2-OHE水平升高（P = 0.03），2-OHE/16 α-OHE 1比值升高（P = 0.04）; CYP 17 C启动子变异等位基因携带者2-OHE水平升高（P = 0.08）。据我们所知，这是第一份显示CYP 1B 1密码子453 G变异等位基因与尿2-OHE和16 α-OHE 1代谢产物之间相关性的报告。应该进行更大规模的研究来证实这些结果。未来识别具有影响雌激素代谢和生物合成的遗传多态性的个体可能有助于描述乳腺癌风险较高的女性，并可以指导这些个体的乳腺癌预防策略。
We examined associations between polymorphisms in genes related to estrogen metabolism (CYP1B1 codon 432G -> C rs#1056836, CYP1B1 codon 453A -> G rs#1800440, COMT codon 158G -> A rs#4680) and biosynthesis (CYP17 T -> C promoter rs#743572, CYP19 exon 4 TTTA repeat) and urinary estrogen metabolites (2-hydroxyestrogens (2-OHE), 16 alpha-hydroxyestrone (16 alpha-OHE1), and their ratio) in a pilot study of 64 pre- and post-menopausal women with a family history of breast cancer. Women were participants in the Metropolitan New York Registry of Breast Cancer Families, one of six international sites of the National Cancer Institute's Breast Cancer Family Registry. We used linear regression to examine the effects of genetic variants on log-transformed urinary estrogen metabolites. After adjusting for menopausal status, BMI, and age, carriers of the CYP1B1 codon 453G variant allele had 31.0% lower levels of 2-OHE (P-value = 0.05) and 40.2% lower levels of 16 alpha-OHE1 (P = 0.01). Results were similar after restricting the analyses to pre-menopausal women (n = 41). Consistent with other studies, among pre-menopausal women, carriers of the COMT codon 158A variant allele had increased 2-OHE levels (P = 0.03) and an increased 2-OHE/16 alpha-OHE1 ratio (P = 0.04); carriers of the CYP17 C promoter variant allele had increased 2-OHE levels (P = 0.08). To our knowledge this is the first report showing associations between the CYP1B1 codon 453G variant allele and urinary 2-OHE and 16 alpha-OHE1 metabolites. Further larger studies should be conducted to confirm these results. Future identification of individuals with genetic polymorphisms that affect estrogen metabolism and biosynthesis may help characterize women at higher breast cancer risk and could guide breast cancer prevention strategies for those individuals.