Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Int J Cancer. 2013 Oct 1;133(7):1751-5. doi: 10.1002/ijc.28160. Epub 2013 Apr 16.
Barrett's esophagus, with gastroesophageal reflux disease and obesity as risk factors, predisposes to esophageal adenocarcinoma (EAC). Recently a British genome wide association study identified two Barrett's esophagus susceptibility loci mapping within the major histocompatibility complex (MHC; rs9257809) and closely to the Forkhead-F1 (FOXF1; rs9936833) coding gene. An interesting issue is whether polymorphisms associated with Barrett's esophagus, are also implicated in esophageal carcinoma (EC), and more specifically EAC genesis. Assessing the individual genetic susceptibility can help identify high risk patients more prone to benefit from surveillance programs. Our hypothesis: Barrett associated MHC and FOXF1 variants modify EC risk in Caucasians. In a Dutch case-control study, 431 patients with EC and 605 healthy controls were included. Polymorphisms at chromosomes 6p21 (MHC) and 16q24 (FOXF1) were determined by means of real-time polymerase chain reaction (RT-PCR). Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals. The FOXF1 rs9936833 variant C allele was associated with an increased EAC susceptibility; OR, [95% CI]; 1.21, [0.99-1.47]. A sex-stratified analysis revealed a similar association in males; 1.24 [1.00-1.55]. The variant MHC rs9257809 G allele as well as the MHC heterozygous AG genotype significantly increased ESCC risk; 1.76 [1.16-2.66] and 1.74 [1.08-2.80], respectively. Sex-stratification showed that the variant G allele was especially present in female patients; 2.32 [1.04-5.20]. In conclusion, this study provides evidence that MHC rs9257809 and FOXF1 rs9936833 variants, associated with Barrett's esophagus, also increase ESCC and EAC susceptibility in Caucasians. FOX proteins are transcription factors involved in organogenesis of the GI tract, while MHC haplotypes are strongly associated with smoking behavior, a crucial risk factor for ESCC. Assessing the individual genetic susceptibility can help identify high risk patients more prone to benefit from (Barrett) surveillance programs.
巴雷特食管，作为胃食管反流病和肥胖的风险因素，易患食管腺癌（EAC）。最近，一项英国全基因组关联研究发现了两个巴雷特食管易感性位点，位于主要组织相容性复合体（MHC；rs9257809）内，并紧密接近叉头框 F1（FOXF1；rs9936833）编码基因。一个有趣的问题是，与巴雷特食管相关的多态性是否也与食管癌（EC）有关，更具体地说，与 EAC 的发生有关。评估个体遗传易感性有助于识别更易受益于监测计划的高危患者。我们的假设：与巴雷特相关的 MHC 和 FOXF1 变体修饰了白种人中的 EC 风险。在一项荷兰病例对照研究中，纳入了 431 名 EC 患者和 605 名健康对照者。通过实时聚合酶链反应（RT-PCR）确定染色体 6p21（MHC）和 16q24（FOXF1）上的多态性。使用逻辑回归分析计算 95%置信区间的优势比。FOXF1 rs9936833 变体 C 等位基因与 EAC 易感性增加相关；OR[95%CI]；1.21[0.99-1.47]。性别分层分析显示男性也存在类似的相关性；1.24[1.00-1.55]。变体 MHC rs9257809 G 等位基因以及 MHC 杂合性 AG 基因型显著增加 ESCC 风险；1.76[1.16-2.66]和 1.74[1.08-2.80]。性别分层显示，变体 G 等位基因尤其存在于女性患者中；2.32[1.04-5.20]。总之，这项研究提供了证据，表明与巴雷特食管相关的 MHC rs9257809 和 FOXF1 rs9936833 变体也增加了白种人中的 ESCC 和 EAC 易感性。FOX 蛋白是参与 GI 道器官发生的转录因子，而 MHC 单倍型与吸烟行为密切相关，吸烟是 ESCC 的一个关键危险因素。评估个体遗传易感性有助于识别更易受益于（巴雷特）监测计划的高危患者。
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