Division of Gastroenterology, University Hospitals-Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
Cancer Epidemiol Biomarkers Prev. 2012 Feb;21(2):376-83. doi: 10.1158/1055-9965.EPI-11-0927. Epub 2011 Dec 16.
Genetic influences may be discerned in families that have multiple affected members and may manifest as an earlier age of cancer diagnosis. In this study, we determine whether cancers develop at an earlier age in multiplex Familial Barrett's Esophagus (FBE) kindreds, defined by 3 or more members affected by Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC).
Information on BE/EAC risk factors and family history was collected from probands at eight tertiary care academic hospitals. Age of cancer diagnosis and other risk factors were compared between nonfamilial (no affected relatives), duplex (two affected relatives), and multiplex (three or more affected relatives) FBE kindreds.
The study included 830 nonfamilial, 274 duplex, and 41 multiplex FBE kindreds with 274, 133, and 43 EAC and 566, 288, and 103 BE cases, respectively. Multivariable mixed models adjusting for familial correlations showed that multiplex kindreds were associated with a younger age of cancer diagnosis (P = 0.0186). Median age of cancer diagnosis was significantly younger in multiplex compared with duplex and nonfamilial kindreds (57 vs. 62 vs. 63 years, respectively, P = 0.0448). Mean body mass index was significantly lower in multiplex kindreds (P = 0.0033), as was smoking (P < 0.0001), and reported regurgitation (P = 0.0014).
Members of multiplex FBE kindreds develop EAC at an earlier age compared with nonfamilial EAC cases. Multiplex kindreds do not have a higher proportion of common risk factors for EAC, suggesting that this aggregation might be related to a genetic factor.
These findings indicate that efforts to identify susceptibility genes for BE and EAC will need to focus on multiplex kindreds.
在有多个患病成员的家族中，可以发现遗传影响，并且可能表现为癌症诊断的年龄更早。在这项研究中，我们确定了是否有更多的多发性家族性 Barrett 食管（FBE）家族成员患有癌症，其定义为 3 个或更多成员患有 Barrett 食管（BE）或食管腺癌（EAC）。
从 8 家三级护理学术医院的先证者那里收集了 BE/EAC 危险因素和家族史的信息。非家族性（无受影响的亲属）、双发性（两个受影响的亲属）和多发性（三个或更多受影响的亲属）FBE 家族之间的癌症诊断年龄和其他危险因素进行了比较。
该研究包括 830 个非家族性、274 个双发性和 41 个多发性 FBE 家族，分别有 274、133 和 43 例 EAC 和 566、288 和 103 例 BE 病例。调整家族相关性的多变量混合模型显示，多发性家族与更年轻的癌症诊断年龄相关（P=0.0186）。与双发性和非家族性家族相比，多发性家族的癌症诊断年龄显著更年轻（分别为 57、62 和 63 岁，P=0.0448）。多发性家族的平均体重指数显著较低（P=0.0033），吸烟（P<0.0001）和反流报告（P=0.0014）也较低。
与非家族性 EAC 病例相比，多发性 FBE 家族成员的 EAC 发病年龄更早。多发性家族并没有更高比例的 EAC 常见危险因素，这表明这种聚集可能与遗传因素有关。
这些发现表明，为 BE 和 EAC 确定易感性基因的努力将需要集中在多发性家族上。
