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: 7661556
• 负责人: LESLIE BERNSTEIN
• 金额: $ 63.29万
• 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/7661556
• 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：高血压与非霍奇金淋巴瘤(NHL)的风险。非霍奇金淋巴瘤的发病率一直在上升 从20世纪40年代开始。女性的发病率低于男性，但很少有危险因素可以解释 发病模式。一种可能的暴露可能解释了男性和女性之间风险模式的差异 女性正在接受激素治疗(HT)。我们先前的研究表明，羟色胺和其他外源性雌激素 然而，另一项研究的结果表明，暴露于环境中会降低女性患高、中级别非霍奇金淋巴瘤的风险 甲状旁腺激素增加了滤泡性非霍奇金淋巴瘤(我们没有研究过的一种类型)的风险。这两项研究的信息都很有限 HT-NHL关系的潜在混杂因素；然而，这些结果耐人寻味，因为 大量证据表明，羟色胺抑制一种有效的B细胞--白介素6(IL-6)的分泌 生长因子在未经治疗的非霍奇金淋巴瘤患者中升高。其他研究表明，雌激素--雌激素 受体复合体直接与IL-6启动子区域的某个位置结合，从而减少IL-6的产生。功能性 已经描述了调节IL-6产生和单倍型的IL-6启动子的多态 结构已经定义。我们建议研究羟色胺对非霍奇金淋巴瘤风险的影响以及IL-6的可能作用 基因类型和单倍型对这种关系的影响。我们将通过开展人口调查来实现这些目标-- 洛杉矶县45-79岁女性B细胞非霍奇金淋巴瘤病例对照研究 说英语的人。我们将招募1060名病例和1060名匹配的对照，他们将提供详细的 面谈中关于高血压和其他各种暴露的信息以及口腔细胞的DNA 样本。将通过核心B使用快速病例确定来确定病例。将确定控制措施 通过核心D，将与年龄、种族/民族和社会经济地位的案例相匹配，基于 他们所在社区的平均收入和教育水平。在这项研究中，我们将讨论：1)是否使用羟色胺 (通过持续时间、配方、年龄和最近使用)影响非霍奇金淋巴瘤风险；2)非霍奇金淋巴瘤风险是否与高血压相关 用途因主要的非霍奇金淋巴瘤亚型而异；3)IL-6基因/单倍型(由核心C衡量)是否会改变这些 关系；以及4)是否使用强迫症、生殖因素、医疗暴露或其他生活方式 特征影响非霍奇金淋巴瘤的风险。