Variation in Age at Cancer Diagnosis in Familial versus Nonfamilial Barrett's Esophagus
Variation in Age at Cancer Diagnosis in Familial versus Nonfamilial Barrett's Esophagus
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DOI：
10.1158/1055-9965.epi-11-0927
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发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Barnholtz-Sloan, Jill S.
中科院分区：
文献类型：
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作者：
Chak, Amitabh;Chen, Yanwen;Barnholtz-Sloan, Jill S.
背景：遗传影响可能在有多个患病成员的家庭中被识别出来，并且可能表现为癌症诊断的早期年龄。在这项研究中，我们确定癌症是否在多家族巴雷特食道（FBE）家族中更早发生，这些家族中有3个或更多的成员患有巴雷特食道（BE）或食管腺癌（EAC）。方法：收集8所三级专科医院先证患者BE/EAC危险因素及家族史资料。比较非家族性（无患病亲属）、双型（有两个患病亲属）和多型（有三个或更多患病亲属）FBE患者的癌症诊断年龄和其他危险因素。结果：本研究纳入非家族性FBE 830例，双相型274例，多相型41例，EAC分别为274例、133例和43例，BE分别为566例、288例和103例。调整家族相关性的多变量混合模型显示，多种类型与较年轻的癌症诊断年龄相关（P = 0.0186）。与双相和非家族性患者相比，多发性患者的中位癌症诊断年龄明显更年轻（分别为57岁、62岁和63岁，P = 0.0448）。多种类儿童的平均体重指数（P = 0.0033）、吸烟（P < 0.0001）和报告的反流（P = 0.0014）均显著降低。结论：与非家族性EAC病例相比，多重FBE类型的成员发生EAC的年龄更早。多重种类的EAC常见危险因素的比例并不高，这表明这种聚集可能与遗传因素有关。影响：这些发现表明，鉴定BE和EAC易感基因的努力将需要集中在多种类型上。癌症流行病学生物标志物；21 (2);376 - 83。AACR (C) 2011。
Background: 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).Methods: 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.Results: 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).Conclusions: 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.Impact: These findings indicate that efforts to identify susceptibility genes for BE and EAC will need to focus on multiplex kindreds. Cancer Epidemiol Biomarkers Prev; 21(2); 376-83. (C)2011 AACR.