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: 6807148
• 负责人: LESLIE BERNSTEIN
• 金额: $ 59.02万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6807148
• 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）的发病率一直在增加。女性的发病率低于男性，但很少有风险因素解释随着时间的推移或按性别划分的发病模式。一种可能解释男性和女性风险模式差异的可能暴露是激素治疗（HT）。我们自己先前的研究表明HT和其他外源性雌激素暴露降低了女性患高和中度NHL的风险，但另一项研究的结果表明HT增加了滤泡性NHL的风险（我们没有研究的亚型）。这两项研究对HT-NHL关系的潜在混杂因素的信息有限;然而，这些结果是有趣的，因为细胞类型的演变可能取决于B细胞成熟和分化，而B细胞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岁女性进行一项以人群为基础的B细胞NHL病例对照研究。我们将招募1173例病例和1173例对照，他们将在面对面访谈期间提供信息，并将提供口腔细胞样本。病例将在2004年7月1日至2007年12月31日之间首次诊断为NHL。对照组将按年龄（5岁年龄组）和人种/种族与病例频率匹配，并将通过调查病例的邻近地区进行识别。 在这项研究中，我们将解决1）是否HT使用（包括具体类型，持续时间，年龄和使用的新近度）影响NHL风险; 2）口服避孕药是否（包括使用的类型、持续时间和年龄）、泌乳抑制剂或其他外源性激素影响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种多态性定义）是否改变这些关系中的任何一种;和5）生殖因素、医疗暴露或生活方式特征是否影响NHL的风险。