HT and Risk of Non-Hodgkin;s Lymphoma (NHL)

HT 和非霍奇金淋巴瘤 (NHL) 的风险

• 批准号: 7492977
• 负责人: LESLIE BERNSTEIN
• 金额: $ 70.85万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7492977
• 关键词: Address; Adult; Affect; Age; Age-Years; B-Cell NonHodgkins Lymphoma; Binding; Case-Control Studies; Cells; Characteristics; Classification; Cohort Studies; Complex; Contraceptive Usage; County; Cytokine Gene; DNA; Drug Formulations; Educational Background; Elevation; Epidemiologic Studies; Estrogen Receptors; Estrogens; Ethnic Origin; Follicular Lymphoma; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; HIV; Haplotypes; High Risk Woman; Histologic; IL6 gene; Incidence; Income; Individual; Interleukin-4; Interleukin-6; Interview; Iowa; Lactation; Life; Life Style; Los Angeles; Lymphoma; Measures; Medical; Menopausal Status; Menopause; Morphology; Natural Killer Cells; Neighborhoods; Nodal; Non-Hodgkin' s Lymphoma; Numbers; Oral; Oral Contraceptives; Ovarian Steroid Hormone; Pathway interactions; Patients; Pattern; Personal Satisfaction; Play; Production; Promoter Regions; Publishing; Race; Rate; Recruitment Activity; Reproductive History; Research; Risk; Risk Factors; Role; Sampling; Schedule; Site; Socioeconomic Status; Standards of Weights and Measures; Structure; System; Woman; Women' s Health; Work; base; cell type; genetic variant; hormone therapy; malignant breast neoplasm; men; promoter; therapy duration

PROJECT B: HT and Risk of Non-Hodgkin's Lymphoma (NHL). NHL rates have been increasing since the 1940s. Incidence is lower among women than among men, yet few risk factors explain the incidence patterns. One possible exposure that may explain differences in risk patterns between men and women is hormone therapy (HT). Our prior research suggested that HT and other exogenous estrogen exposures decrease women's risk of high and intermediate grade NHL, yet results of another study suggest HT increases risk of follicular NHL (a type that we did not study). Both studies had limited information on potential confounders of an HT-NHL relationship; nevertheless these results are intriguing because a preponderance of evidence suggests that HT suppresses secretion of interleukin-6 (IL-6), a potent B-cell growth factor that is elevated in untreated NHL patients. Other studies have shown that estrogen-estrogen receptor complexes bind directly to a site in the IL-6 promoter region and reduce IL-6 production. Functional polymorphisms have been described in the IL-6 promoter that regulate IL-6 production and the haplotype structure has been defined. We propose to study the effect of HT on NHL risk and the possible effect of IL-6 genotypes and haplotypes on this relationship. We will accomplish these aims by conducting apopulation- based case-control study of B-cell NHL among women 45-79 years of age, living in Los Angeles County, who are English-speaking. We will recruit 1060 cases and 1060 matched controls, who will provide detailed information on HT and various other exposures in a personal interview as well as DNA via buccal cell sample. Cases will be identified using rapid case ascertainment through Core B. Controls will be identified through Core D and will be matched to cases on age, race/ethnicity, and socioeconomic status based on mean income and education level of their neighborhood. In this study, we will address: 1) whether HT use (by duration, formulation, age and recency of use) affects NHL risk; 2) whether NHL risk associated with HT use varies by major NHL subtype; 3) whether IL-6 genotype/haplotype (measured by Core C) modifies these relationships; and 4) whether OC use, reproductive factors, medical exposures or other lifestyle characteristics influence risk of NHL.

项目 B：HT 和非霍奇金淋巴瘤 (NHL) 的风险。 NHL 发病率一直在上升 自20世纪40年代以来。女性的发病率低于男性，但很少有危险因素可以解释这一现象 发病模式。一种可能的暴露可以解释男性和女性之间风险模式的差异 女性则采用激素疗法（HT）。我们之前的研究表明 HT 和其他外源性雌激素 接触可降低女性罹患高中级 NHL 的风险，但另一项研究的结果表明 HT 会增加滤泡性 NHL（我们未研究的一种类型）的风险。这两项研究的信息都有限 HT-NHL 关系的潜在混杂因素；尽管如此，这些结果还是很有趣，因为 大量证据表明 HT 抑制白细胞介素 6 (IL-6)（一种有效的 B 细胞）的分泌 未经治疗的 NHL 患者中生长因子升高。其他研究表明，雌激素-雌激素 受体复合物直接与 IL-6 启动子区域的位点结合并减少 IL-6 的产生。功能性 调节 IL-6 产生和单倍型的 IL-6 启动子中已描述了多态性 结构已被定义。我们建议研究 HT 对 NHL 风险的影响以及 IL-6 的可能影响 这种关系的基因型和单倍型。我们将通过开展人口统计来实现这些目标 基于居住在洛杉矶县 45-79 岁女性 B 细胞 NHL 的病例对照研究， 谁是说英语的。我们将招募1060个病例和1060个匹配对照，他们将提供详细的 个人访谈中有关 HT 和各种其他暴露的信息以及通过口腔细胞获得的 DNA 样本。将通过核心 B 使用快速病例查明来识别病例。将确定控制措施 通过核心 D，并将根据年龄、种族/民族和社会经济地位与案例进行匹配 他们的邻居的平均收入和教育水平。在本研究中，我们将解决：1）是否使用 HT （根据持续时间、配方、年龄和使用新近程度）影响 NHL 风险； 2) NHL风险是否与HT相关 用途因主要 NHL 亚型而异； 3) IL-6基因型/单倍型（由核心C测量）是否改变这些 关系； 4) 是否使用口服避孕药、生殖因素、医疗暴露或其他生活方式 特征影响 NHL 的风险。