Exogenous Hormones, IL-6 and NHL Risk in Women

女性的外源激素、IL-6 和 NHL 风险

• 批准号: 6922055
• 负责人: LESLIE BERNSTEIN
• 金额: $ 5.16万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922055
• 关键词: B cell lymphoma; B lymphocyte; age difference; cancer risk; clinical research; disease /therapy duration; estrogens; female; female reproductive system; genetic polymorphism; genetic susceptibility; genotype; histology; hormone related neoplasm /cancer; hormone therapy; human subject; interleukin 6; interview; lactation; lifestyle; mutant; neoplasm /cancer epidemiology; oral contraceptives; progesterone; women' s health

DESCRIPTION (provided by applicant): Non-Hodgkin's lymphoma (NHL) rates have been increasing since the 1940s. Incidence is lower among women than among men, yet few risk factors explain incidence patterns over time or by gender. One possible exposure that may explain differences in risk patterns of men and women is hormone therapy (HT). Our own prior research suggested HT and other exogenous estrogen exposures decrease women's risk of high and intermediate NHL, yet results of another study suggest HT increases risk of follicular NHL (a subtype we did not study). Both studies had limited information on potential confounders of an HT-NHL relationship; nevertheless these results are intriguing because the evolution of cell type may depend on B-cell maturation and differentiation which is influenced by levels of interleukin-6 (IL-6); these, in turn, are influenced by the individual's IL-6 genotype and may be impacted by estrogen and progesterone exposure. We propose to conduct a population-based case-control study of B-cell NHL among women 20- 79 years of age, living in Los Angeles County, who are English speaking. We will recruit 1173 cases and 1173 controls, who will provide information during an in-person interview and will provide a buccal cell sample. Cases will have a first primary NHL diagnosis that occurs between July 1, 2004 and December 31, 2007. Controls will be frequency matched to cases by age (5 year age groups) and race/ethnicity and will be identified by surveying the neighborhoods of cases. In this study we will address 1) whether HT use (including specific types, durations, ages and recency of use) affects NHL risk; 2) whether oral contraceptives (including types, durations, and ages of use), lactation suppressants or other exogenous hormones affect NHL risk; 3) whether NHL risk associated with use of exogenous hormones varies by histologic subtype; 4) whether IL-6 genotype (as defined by 4 polymorphisms) modifies any of these relationships; and 5) whether reproductive factors, medical exposures or lifestyle characteristics influence risk of NHL.

描述（由申请人提供）：自 20 世纪 40 年代以来，非霍奇金淋巴瘤 (NHL) 发病率一直在上升。女性的发病率低于男性，但很少有危险因素可以解释随时间或性别的发病模式。可以解释男性和女性风险模式差异的一种可能的暴露是激素治疗（HT）。我们自己之前的研究表明，HT 和其他外源性雌激素暴露会降低女性患高度和中度 NHL 的风险，但另一项研究的结果表明，HT 会增加滤泡性 NHL（我们没有研究的亚型）的风险。这两项研究对于 HT-NHL 关系的潜在混杂因素的信息有限；然而，这些结果很有趣，因为细胞类型的进化可能取决于 B 细胞的成熟和分化，而 B 细胞的成熟和分化受白细胞介素 6 (IL-6) 水平的影响；这些反过来又受到个体 IL-6 基因型的影响，并可能受到雌激素和孕激素暴露的影响。 我们建议对居住在洛杉矶县讲英语的 20-79 岁女性进行一项基于人群的 B 细胞 NHL 病例对照研究。我们将招募 1173 名病例和 1173 名对照，他们将在面对面访谈中提供信息，并提供口腔细胞样本。病例将在 2004 年 7 月 1 日至 2007 年 12 月 31 日之间进行首次 NHL 初步诊断。对照将按年龄（5 岁年龄组）和种族/族裔与病例进行频率匹配，并将通过调查病例邻近地区来确定。 在本研究中，我们将解决 1) HT 的使用（包括特定类型、持续时间、年龄和新近使用）是否会影响 NHL 风险； 2）口服避孕药（包括种类、持续时间和使用年龄）、哺乳抑制剂或其他外源性激素是否影响NHL风险； 3) 与使用外源性激素相关的 NHL 风险是否因组织学亚型而异； 4) IL-6基因型（由4个多态性定义）是否改变这些关系； 5) 生殖因素、医疗暴露或生活方式特征是否影响 NHL 风险。