Rudolph Rebecca E, Vaughan Thomas L, Kristal Alan R, Blount Patricia L, Levine Douglas S, Galipeau Patricia C, Prevo Laura J, Sanchez Carissa A, Rabinovitch Peter S, Reid Brian J
Cancer Prevention and Trials Program, Fred Hutchinson Cancer Research Center, and Department of Medicine, University of Washington, Seattle 98109-1024 , USA.
J Natl Cancer Inst. 2003 May 21;95(10):750-7. doi: 10.1093/jnci/95.10.750.
Persons with Barrett's esophagus have a substantially greater risk of esophageal adenocarcinoma than the general population. Higher serum selenium levels have been associated with a reduced risk of several cancers; however, their association with the risk of esophageal adenocarcinoma is unknown. We used a cross-sectional study to investigate the relationship between serum selenium levels and markers of neoplastic progression among persons with Barrett's esophagus.
Medical history, blood, and esophageal tissue specimens were collected from 399 members of a cohort study of Barrett's esophagus patients undergoing endoscopic surveillance. Serum selenium levels were measured by flameless atomic absorption spectrophotometry. DNA content of tissue samples was measured by flow cytometry. Loss of heterozygosity (LOH) at 9p and 17p, chromosomal regions which include the p16 and p53 tumor suppressors, respectively, was detected by automated fluorescent genotyping. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided.
Persons with serum selenium levels in the upper three quartiles (i.e., >1.5 micro M) were less likely to have high-grade dysplasia (OR = 0.5, 95% CI = 0.3 to 0.9) or aneuploidy (OR = 0.4, 95% CI = 0.2 to 0.8) than those with levels in the lowest quartile. Serum selenium levels in the upper three quartiles were associated with similar reductions in risk of 17p (p53) LOH (OR = 0.5, 95% CI = 0.2 to 0.9) and increased 4N fraction (OR = 0.6, 95% CI = 0.3 to 1.2). By contrast, serum selenium levels were not associated with 9p (p16) LOH (OR = 1.0, 95% CI = 0.5 to 1.7), a marker that appears early in neoplastic progression.
Our preliminary results, from a cross-sectional analysis with biologic markers, suggest that higher serum selenium levels may be associated with a reduced risk of esophageal adenocarcinoma among persons with Barrett's esophagus. Because serum selenium was not associated with 9p (p16) LOH, we speculate that selenium may act primarily at later stages of progression toward adenocarcinoma.
巴雷特食管患者患食管腺癌的风险明显高于普通人群。较高的血清硒水平与几种癌症风险降低相关；然而，其与食管腺癌风险的关联尚不清楚。我们采用横断面研究来调查巴雷特食管患者血清硒水平与肿瘤进展标志物之间的关系。
从399名接受内镜监测的巴雷特食管患者队列研究的成员中收集病史、血液和食管组织标本。采用无火焰原子吸收分光光度法测量血清硒水平。通过流式细胞术测量组织样本的DNA含量。通过自动荧光基因分型检测9p和17p染色体区域的杂合性缺失（LOH），这两个区域分别包含p16和p53肿瘤抑制基因。采用逻辑回归计算比值比（OR）和95%置信区间（CI）。所有统计检验均为双侧检验。
血清硒水平处于上三个四分位数（即>1.5微摩尔）的患者与处于最低四分位数的患者相比，发生高级别异型增生（OR = 0.5，95% CI = 0.3至0.9）或非整倍体（OR = 0.4，95% CI = 0.2至0.8）的可能性较小。上三个四分位数的血清硒水平与17p（p53）LOH风险的类似降低（OR = 0.5，95% CI = 0.2至0.9）和4N分数增加（OR = 0.6，95% CI = 0.3至1.2）相关。相比之下，血清硒水平与9p（p16）LOH无关（OR = 1.0，95% CI = 0.5至1.7），9p（p16）LOH是肿瘤进展早期出现的一个标志物。
我们通过对生物标志物进行横断面分析得出的初步结果表明，较高的血清硒水平可能与巴雷特食管患者食管腺癌风险降低相关。由于血清硒与9p（p16）LOH无关，我们推测硒可能主要在向腺癌进展的后期起作用。
