Tworoger Shelley S, Chubak Jessica, Aiello Erin J, Ulrich Cornelia M, Atkinson Charlotte, Potter John D, Yasui Yutaka, Stapleton Patricia L, Lampe Johanna W, Farin Federico M, Stanczyk Frank Z, McTiernan Anne
The Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program, Seattle, Washington, USA.
Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):94-101. doi: 10.1158/1055-9965.epi-03-0026.
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)], CYP1B1 (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.
循环雌激素浓度高的女性患乳腺癌的风险增加；因此，了解包括基因变异在内的影响雌激素浓度的因素非常重要。已经确定了几种可能影响性激素浓度的基因多态性，包括CYP17（5'-非翻译区T→C）、CYP19 [内含子4（TTTA）(n = 7 - 13)和一个3bp缺失（-3）]、CYP1B1（Val(432)Leu）和COMT（Val(108/158)Met）。我们利用一项运动临床试验随机分组前访视的数据，研究了这些多态性与171名绝经后女性血清雌激素、雄激素、性激素结合球蛋白浓度以及尿中2-和16α-羟雌酮浓度之间的关联。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CYP19 7r(-3)等位基因的女性雌酮浓度低26%（P < 0.001），雌二醇浓度低19%（P = 0.01），游离雌二醇浓度低23%（P = 0.01），性激素结合球蛋白浓度高22%（P = 0.06）。与非携带者相比，携带至少一个CYP19 8r等位基因的女性雌酮浓度高20%（P = 0.003），雌二醇浓度高18%（P = 0.02），游离雌二醇浓度高21%（P = 0.01）。与Val/Val基因型女性相比，COMT Met/Met基因型女性的2-羟雌酮浓度高28%（P = 0.08），16α-羟雌酮浓度高31%（P = 0.02）。CYP17和CYP1B1与血清雄激素浓度之间几乎没有发现关联。这项研究提供了进一步的证据，表明基因变异可能会显著改变未接受激素治疗的绝经后女性的性激素浓度。
