García-Closas Montserrat, Herbstman Julie, Schiffman Mark, Glass Andrew, Dorgan Joanne F
Division of Cancer Epidemiology and Genetics, National Cancer Institute/NIH, 6120 Executive Boulevard, Bethesda, MD 20852-7234, USA.
Int J Cancer. 2002 Nov 10;102(2):172-8. doi: 10.1002/ijc.10651.
Reproductive characteristics, alcohol intake and polymorphisms in genes encoding sex-steroid metabolizing enzymes might influence the risk of hormone-related cancers by changing circulating concentrations of sex hormones. The relationship between these factors and serum concentrations of estradiol, progesterone, androstenedione, testosterone and DHEA was evaluated in a cross-sectional study of 218 pre-menopausal women from Kaiser Permanente Health Plan in Portland, Oregon. Risk factor information was obtained from questionnaires and hormone serum concentrations were determined by radioimmunoassays. Genotypes for CYP11A 5'UTR(tttta)n, CYP17 5'-UTR -34 T>C, CYP19 IVS4(ttta)n, CYP1B1 (L432V and S453N) and COMT (V158M) were determined from genomic DNA samples. Increasing number of full-term pregnancies was associated with a significant decrease in late-follicular progesterone levels (p-trend = 0.03). Increasing alcohol consumption was associated with higher estradiol levels averaged through the menstrual cycle (p-trend = 0.009) and higher progesterone levels during luteal phase (p-trend = 0.04). Androstenedione and testosterone levels were higher among light to moderate drinkers compared to non-drinkers, although we only observe a significant trend with increasing levels of alcohol consumption for androstenedione. Women heterozygous or homozygous for the CYP1B1 L432V or the S453N polymorphisms had increased luteal estradiol levels (p-value = 0.04 for L432V and 0.04 for S453N). None of the other factors evaluated was significantly associated with serum concentration of hormones. In conclusion, results from this cross-sectional study of pre-menopausal women provide support for an association between light to moderate alcohol intake and elevated levels of estrogen and androgen levels. Our data suggest that circulating levels of progesterone might be related to parity and alcohol consumption, however the biological plausibility of the observed associations is unclear. We found little support for an influence of the evaluated genetic polymorphisms in the steroid synthesis and metabolism pathway on serum hormone levels, except for a possible effect of the CYP1B1 L432V and S453N polymorphisms on serum estradiol levels.
生殖特征、酒精摄入量以及编码性甾体代谢酶的基因多态性可能通过改变循环中性激素浓度来影响激素相关癌症的风险。在一项针对俄勒冈州波特兰市凯撒医疗集团健康计划中的218名绝经前女性的横断面研究中，评估了这些因素与雌二醇、孕酮、雄烯二酮、睾酮和脱氢表雄酮血清浓度之间的关系。危险因素信息通过问卷获取，激素血清浓度通过放射免疫测定法测定。从基因组DNA样本中确定了CYP11A 5'UTR(tttta)n、CYP17 5'-UTR -34 T>C、CYP19 IVS4(ttta)n、CYP1B1 (L432V和S453N)和COMT (V158M)的基因型。足月妊娠次数增加与卵泡晚期孕酮水平显著降低相关(p趋势=0.03)。酒精摄入量增加与整个月经周期平均雌二醇水平升高相关(p趋势=0.009)以及黄体期孕酮水平升高相关(p趋势=0.04)。与不饮酒者相比，轻度至中度饮酒者的雄烯二酮和睾酮水平更高，尽管我们仅观察到雄烯二酮随着酒精摄入量增加有显著趋势。CYP1B1 L432V或S453N多态性的杂合或纯合女性黄体期雌二醇水平升高(L432V的p值=0.04，S453N的p值=0.当与其他任何解释或说明。
Reproductive characteristics, alcohol intake and polymorphisms in genes encoding sex-steroid metabolizing enzymes might influence the risk of hormone-related cancers by changing circulating concentrations of sex hormones. The relationship between these factors and serum concentrations of estradiol, progesterone, androstenedione, testosterone and DHEA was evaluated in a cross-sectional study of 21,8 pre-menopausal women from Kaiser Permanente Health Plan in Portland, Oregon. Risk factor information was obtained from questionnaires and hormone serum concentrations were determined by radioimmunoassays. Genotypes for CYP11A 5'UTR(tttta)n, CYP17 5'-UTR -34 T>C, CYP19 IVS4(ttta)n, CYP1B1 (L432V and S453N) and COMT (V158M) were determined from genomic DNA samples. Increasing number of full-term pregnancies was associated with a significant decrease in late-follicular progesterone levels (p-trend = 0.03). Increasing alcohol consumption was associated with higher estradiol levels averaged through the menstrual cycle (p-trend = 0.009) and higher progesterone levels during luteal phase (p-trend = 0.04). Androstenedione and testosterone levels were higher among light to moderate drinkers compared to non-drinkers, although we only observe a significant trend with increasing levels of alcohol consumption for androstenedione. Women heterozygous or homozygous for the CYP1B1 L432V or the S453N polymorphisms had increased luteal estradiol levels (p-value = 0.04 for L432V and 0.04 for S453N). None of the other factors evaluated was significantly associated with serum concentration of hormones. In conclusion, results from this cross-sectional study of pre-menopausal women provide support for an association between light to moderate alcohol intake and elevated levels of estrogen and androgen levels. Our data suggest that circulating levels of progesterone might be related to parity and alcohol consumption, however the biological plausibility of the observed associations is unclear. We found little support for an influence of the evaluated genetic polymorphisms in the steroid synthesis and metabolism pathway on serum hormone levels, except for a possible effect of the CYP1B1 L432V and S453N polymorphisms on serum estradiol levels.
生殖特征、酒精摄入量以及编码性甾体代谢酶的基因多态性可能通过改变循环中性激素浓度来影响激素相关癌症的风险。在一项针对来自俄勒冈州波特兰市凯撒医疗集团健康计划的218名绝经前女性的横断面研究中，评估了这些因素与雌二醇、孕酮、雄烯二酮、睾酮和脱氢表雄酮血清浓度之间的关系。危险因素信息通过问卷获取，激素血清浓度通过放射免疫测定法测定。从基因组DNA样本中确定了CYP11A 5'UTR(tttta)n、CYP17 5'-UTR -34 T>C、CYP19 IVS4(ttta)n、CYP1B1 (L432V和S453N)和COMT (V158M)的基因型。足月妊娠次数增加与卵泡晚期孕酮水平显著降低相关（p趋势=0.03）。酒精摄入量增加与整个月经周期平均雌二醇水平升高相关（p趋势=0.009）以及黄体期孕酮水平升高相关（p趋势=0.04）。与不饮酒者相比，轻度至中度饮酒者的雄烯二酮和睾酮水平更高，尽管我们仅观察到雄烯二酮随着酒精摄入量增加有显著趋势。CYP1B1 L432V或S453N多态性的杂合或纯合女性黄体期雌二醇水平升高（L432V的p值=0.04，S453N的p值=0.04）。评估的其他因素均与激素血清浓度无显著关联。总之，这项绝经前女性横断面研究的结果支持了轻度至中度酒精摄入与雌激素和雄激素水平升高之间的关联。我们的数据表明，孕酮的循环水平可能与产次和酒精消费有关，然而观察到的关联的生物学合理性尚不清楚。除了CYP1B1 L432V和S453N多态性对血清雌二醇水平可能有影响外，我们几乎没有发现所评估的类固醇合成和代谢途径中的基因多态性对血清激素水平有影响的证据。
