Haile R W, Cortessis V K, Millikan R, Ingles S, Aragaki C C, Richardson L, Thompson W D, Paganini-Hill A, Sparkes R S
Department of Epidemiology, University of California, Los Angeles 90024.
Cancer Res. 1993 Jan 15;53(2):212-4.
We report here results of a linkage analysis of a marker in 35 families in which the proband had premenopausal bilateral breast cancer. This group is of particular interest given their high family risk and the question of etiological heterogeneity. Probands were ascertained from cancer registries in Los Angeles County and Connecticut and major hospitals in Montréal and Québec. Assuming no residual heterogeneity and summing lod scores over all families, we obtained strong evidence against tight linkage (e.g., lod score at theta = 0.000001 is -3.39). To address the issue of heterogeneity, we performed admixture and predivided sample analyses. Using an admixture model we were able to reject the hypothesis of no linkage versus that of linkage with homogeneity (P = 0.045). However, we were unable to reject the hypothesis of no linkage versus linkage with heterogeneity (P = 0.119) or to distinguish between linkage with homogeneity and linkage with heterogeneity (P = 0.500). Predivided sample analyses based upon age of onset, pathological characteristics, time between diagnoses of the breast cancers in each bilateral proband, and the span of ages at diagnoses within a family did not discriminate between apparently linked and unlinked families.
我们在此报告对35个家族中一个标记物进行连锁分析的结果，这些家族中的先证者患有绝经前双侧乳腺癌。鉴于其高家族风险以及病因异质性问题，这一群体尤其令人关注。先证者是从洛杉矶县和康涅狄格州的癌症登记处以及蒙特利尔和魁北克的主要医院确定的。假设不存在残余异质性并对所有家族的对数优势比分进行求和，我们获得了反对紧密连锁的有力证据（例如，在θ = 0.000001时对数优势比分为 -3.39）。为了解决异质性问题，我们进行了混合分析和预先划分样本分析。使用混合模型，我们能够拒绝无连锁假设与同质连锁假设（P = 0.045）。然而，我们无法拒绝无连锁假设与异质连锁假设（P = 0.119），也无法区分同质连锁与异质连锁（P = 0.500）。基于发病年龄、病理特征、每个双侧先证者双侧乳腺癌诊断之间的时间以及家族内诊断时的年龄跨度进行的预先划分样本分析，并未区分出明显连锁和不连锁的家族。
