Association of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women
Association of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women
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DOI：
10.1158/1055-9965.epi-03-0026
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发表时间：
2004-01-01
影响因子：
3.8
通讯作者：
McTiernan, A
中科院分区：
文献类型：
--
作者：
Tworoger, SS;Chubak, J;McTiernan, A
高循环雌激素浓度的女性患乳腺癌的风险增加;因此，重要的是要了解影响雌激素浓度的因素，包括遗传变异性。已经鉴定了几种可能影响性激素浓度的遗传多态性，包括CYP 17（5 '-非翻译区T->C）、CYP 19 [内含子4（TTTA）（n = 7-13.）和3-bp缺失（-3）]、CYPIBI（瓦尔（432）Leu）和COMT（瓦尔（108）/（158）Met）。我们研究了这些多态性与雌激素、雄激素和性激素结合球蛋白的血清浓度以及171名绝经后妇女2-和16 α-羟基雌酮的尿浓度之间的关系，使用的数据来自运动临床试验的随机化前访问。参与者久坐不动，未接受激素治疗，体重指数>24.0。与非携带者相比，携带两个CYP 19 7 r（-3）等位基因的女性雌酮降低26%（P < 0.001），雌二醇降低19%（P = 0.01），游离雌二醇降低23%（P = 0.01），性激素结合球蛋白浓度升高22%（P = 0.06）。与非携带者相比，携带至少一个CYP 19 8 r等位基因的妇女雌酮高20%（P = 0.003），雌二醇高18%（P = 0.02），游离雌二醇浓度高21%（P = 0.01）。与瓦尔/瓦尔基因型妇女相比，COMT Met/Met基因型妇女的2-羟基雌酮浓度高28%（P = 0.08），16 α-羟基雌酮浓度高31%（P = 0.02）。CYP 17和CYP 1B 1或血清雄激素浓度几乎没有相关性。这项研究提供了进一步的证据表明，遗传变异可能会明显改变绝经后妇女不采取激素治疗的性激素浓度。
Women with high circulating estrogen concentrations have an increased risk of breast cancer; thus, it is important to understand factors, including genetic variability, that influence estrogen concentrations. Several genetic polymorphisms that may influence sex hormone concentrations have been identified, including CYP17 (5'-untranslated region T-->C), CYP19 [intron 4 (TTTA)(n = 7-13.) and a 3-bp deletion (-3)], CYPIBI (Val(432) Leu), and COMT (Val(108)/(158)Met). We examined associations between these polymorphisms and serum concentrations of estrogens, androgens, and sex hormone-binding globulin and urinary concentrations of 2- and 16alpha-hydroxyestrone in 171 postmenopausal women, using data from the prerandomization visit of an exercise clinical trial. Participants were sedentary, not taking hormone therapy, and had a body mass index >24.0. Compared with noncarriers, women carrying two CYP19 7r(-3) alleles had 26% lower estrone (P < 0.001), 19% lower estradiol (P = 0.01), 23% lower free estradiol (P = 0.01), and 22% higher sex hormone-binding globulin concentrations (P = 0.06). Compared with noncarriers, women carrying at least one CYP19 8r allele had 20% higher estrone (P = 0.003), 18% higher estradiol (P = 0.02), and 21% higher free estradiol concentrations (P = 0.01). Women with the COMT Met/Met genotype had 28% higher 2-hydroxyestrone (P = 0.08) and 31% higher 16alpha-hydroxyestrone concentrations (P = 0.02), compared with Val/Val women. Few associations were found for CYP17 and CYP1B1 or with serum androgen concentrations. This study provides further evidence that genetic variation may appreciably alter sex hormone concentrations in postmenopausal women not taking hormone therapy.