ENDOMETRIAL CANCER AND CYP1A1, GSTM1 AND POLYMORPHISMS

子宫内膜癌与 CYP1A1、GSTM1 和多态性

• 批准号: 2801425
• 负责人: CHU S CHEN
• 金额: $ 8.65万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2801425
• 关键词: blood chemistry; cancer risk; catechol methyltransferase; clinical research; cytochrome P450; endometrium; estrogens; female; genetic polymorphism; genotype; glutathione transferase; hormone related neoplasm /cancer; hormone therapy; human subject; interview; neoplasm /cancer epidemiology; neoplasm /cancer genetics; polymerase chain reaction; restriction fragment length polymorphism; smoking; steroid hormone metabolism; unspecific monooxygenase; uterus neoplasms

DESCRIPTION: (Applicant's Description) Women who smoke cigarettes have about half the risk of endometrial cancer of non-smokers. Female smokers have been observed to have an increase in 2-hydroxylation of estrogens, and this increased 2-hydroxylation has been suggested as a mechanism to explain the apparent antiestrogenic effect of cigarette smoke. Polymorphisms in several genes involved in metabolizing potential carcinogens in cigarette smoke have been related to an increased risk of lung cancer. One of these genes is also involved in 2-hydroxylation of estrogens. Thus, it might be anticipated that women who have the high-risk genotypes, in terms of lung cancer, would have a reduced risk of a condition such as endometrial cancer, whose incidence is reduced by cigarette smoking. However, in a recent small case-control study, a strong, positive relationship between the presence of some of the polymorphisms in these genes and endometrial cancer risk was reported. In our proposed population-based case-control study, we will explore whether polymorphisms in some of these genes are associated with endometrial cancer risk. The genes of interest are: cytochrome P450 1A1 (CYP1A1), glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), and catechol-O-methyltransferase (COMT). Cases and controls will be drawn from our funded study of continuous combined hormone replacement therapy and endometrial cancer. Cases are women ages 50-69 years with incident endometrial cancer diagnosed between 6/l/97 and 7/31/00, who reside in western Washington. Controls are women recruited through random-digit dialing (ages 50-64 years) and Health Care Financing Administration files (ages 65-69 years), who reside in the same geographic area. In the proposed study, 175 cases and 175 controls will be asked to provide a blood specimen at the time of interview. Using purified DNA from these blood samples, the genotypes of interest will be assayed using PCR and RFLPs. Differences in the distributions of genotypes between cases and controls will be assessed in the whole study population, as well as in sub-groups of women defined by cigarette smoking history and use of hormone replacement therapy (HRT). Since endometrial cancer is strongly hormone-related, the results of this study could have relevance for other, more common cancers whose relation to hormones is not so straightforward. Additionally, this information potentially could be used to predict a woman's sensitivity to the carcinogenic effects of HRT, and thus bear on a woman's decision regarding long-term use of HRT.

描述：（申请人的描述）吸烟的妇女有 患子宫内膜癌的风险是不吸烟者的一半。 女性吸烟者 已观察到雌激素的2-羟基化增加， 这种增加的2-羟基化被认为是解释 香烟烟雾明显的抗雌激素作用。 多态性 几个参与香烟致癌物代谢的基因 吸烟与肺癌风险增加有关。 其中一 基因也参与雌激素的2-羟基化。 因此， 预计具有高风险基因型的女性，就肺功能而言， 癌症，会降低患子宫内膜癌等疾病的风险， 其发病率因吸烟而降低。 然而，在最近的一次小 病例对照研究显示， 这些基因中的一些多态性与子宫内膜癌风险之间的关系是 报道 在我们提出的基于人群的病例对照研究中，我们将探讨是否 其中一些基因的多态性与子宫内膜癌相关 风险 感兴趣的基因是：细胞色素P450 1A 1（CYP 1A 1）， 谷胱甘肽-S-转移酶M1（GSTM 1）和T1（GSTT 1），和 儿茶酚-O-甲基转移酶（COMT）。 病例和对照将来自我们资助的持续性研究， 联合激素替代疗法和子宫内膜癌。 案件 年龄50-69岁的女性，诊断为子宫内膜癌， 1997年6月1日和2000年7月31日，居住在华盛顿西部。 对照组为女性 通过随机数字拨号（年龄50-64岁）和医疗保健招募 财务管理档案（年龄65-69岁），居住在同一个 地理区域。 在拟议的研究中，将有175例病例和175例对照， 在面试时被要求提供血液样本。 使用纯化 从这些血液样本的DNA中，将测定感兴趣的基因型 使用PCR和RFLP。 病例组与对照组基因型分布的差异 将在整个研究人群以及以下亚组中进行评估 根据吸烟史和使用激素替代品定义的女性 激素替代疗法（HRT）。 由于子宫内膜癌是强烈相关的， 这项研究的结果可能与其他更常见的癌症有关 它与荷尔蒙的关系并不简单。 而且这个 这些信息可能被用来预测一个女人对 激素替代疗法的致癌作用，从而影响妇女的决定 长期使用激素替代疗法