Exogenous Hormones, IL-6 and NHL Risk in Women

描述(申请人提供)：自1940年代以来，非霍奇金淋巴瘤(NHL)的发病率一直在上升。女性的发病率低于男性，但很少有危险因素解释随时间或性别的发病率模式。一种可能的暴露是激素治疗(HT)，这可能解释了男性和女性风险模式的差异。我们先前的研究表明，羟色胺和其他外源性雌激素暴露降低了女性患高度和中度非霍奇金淋巴瘤的风险，而另一项研究的结果表明，羟色胺增加了滤泡性非霍奇金淋巴瘤(我们没有研究的亚型)的风险。这两项研究都对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依赖于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，而这些又受个体的IL-6基因型别的影响，并可能受到雌激素和孕激素暴露的影响。 我们建议在居住在洛杉矶县、说英语的20-79岁女性中进行一项基于人群的B细胞非霍奇金淋巴瘤病例对照研究。我们将招募1173名病例和1173名对照，他们将在面谈中提供信息，并提供口腔细胞样本。这些病例将在2004年7月1日至2007年12月31日之间首次被诊断为NHL。对照将按年龄(5岁年龄组)和种族/民族与病例相匹配，并将通过调查病例的社区来确定。 在这项研究中，我们将讨论1)使用羟色胺(包括特定类型、持续时间、年龄和最近使用)是否影响NHL风险；2)口服避孕药(包括使用类型、持续时间和年龄)、哺乳抑制药或其他外源性激素是否影响NHL风险；3)使用外源性激素引起的NHL风险是否因组织学亚型而异；4)IL-6基因(由4个多态性定义)是否改变这些关系；以及5)生殖因素、医疗暴露或生活方式特征是否影响NHL风险。

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.