Institute of Pathology Celle, Wittingerstrasse 14, 29223 Celle, Germany.
J Cancer Res Clin Oncol. 2010 Jun;136(6):795-802. doi: 10.1007/s00432-009-0719-9. Epub 2009 Nov 19.
The deleted-in-polyposis1-like1 (DP1L1) gene displays pro-apoptotic activity and was proposed to be a tumor suppressor. It locates on chromosome 19p13.3, which harbors the locus for Peutz-Jeghers-Syndrome and is deleted in various tumors. We analyzed the association of DP1L1 polymorphisms with colon cancer, and cancer-associated Ulcerative colitis and Crohn's disease.
Fifty-eight patients with colon cancer, 18 with Ulcerative colitis, 18 with Crohn's disease, and 70 control individuals were genotyped for SNPs at positions 992 and 996 of DP1L1 cDNA.
Homozygous carriers of 992A alleles comprised 16% of the control group but were significantly increased in colon cancer with a frequency of 36% (P = 0.013 cancer vs control). Homozygous 991-A was also elevated in Ulcerative colitis (N = 18) with a frequency of 33%. In contrast, 18 patients with Crohn's disease showed no difference in frequency of 992AA (22%) compared to control. The A-allele of the adjacent C996A polymorphism has a low frequency (3.5%) in the control population, but significantly increased frequency of 13% in colon cancer (P = 0.0149 for allele frequency, Fisher's exact). 996-A allele frequency is also increased in inflammatory bowel disease (IBD): 22% of Ulcerative colitis- and 50% of Crohn's disease-patients were heterozygous carriers of 996-A (P = 0.052 for CU and P < 0.0001 for MC vs controls).
DP1L1 polymorphisms are associated with colon cancer and IBD. This indicates that DP1L1 plays a functional role in these conditions. Thus DP1L1 may be a diagnostic and therapeutic target for colon cancer and IBD.
缺失于多发性息肉综合征 1 样 1（DP1L1）基因具有促凋亡活性，被提议为肿瘤抑制因子。它位于 19p13.3 染色体上，该染色体含有 Peutz-Jeghers 综合征的基因座，并且在各种肿瘤中缺失。我们分析了 DP1L1 多态性与结肠癌、与癌症相关的溃疡性结肠炎和克罗恩病的关联。
对 58 例结肠癌患者、18 例溃疡性结肠炎患者、18 例克罗恩病患者和 70 名对照个体的 DP1L1 cDNA 位置 992 和 996 的 SNP 进行基因分型。
992A 等位基因纯合子携带者在对照组中占 16%，但在结肠癌中显著增加至 36%（P=0.013 癌症与对照组）。溃疡性结肠炎（N=18）中 991-A 纯合子也升高，频率为 33%。相比之下，18 例克罗恩病患者的 992AA 频率（22%）与对照组无差异。相邻 C996A 多态性的 A 等位基因在对照组中的频率较低（3.5%），但在结肠癌中显著增加至 13%（P=0.0149 等位基因频率，Fisher 精确检验）。炎症性肠病（IBD）中 996-A 等位基因频率也升高：溃疡性结肠炎患者中 22%和克罗恩病患者中 50%为 996-A 的杂合子携带者（UC 组 P=0.052，MC 组 P<0.0001 与对照组相比）。
DP1L1 多态性与结肠癌和 IBD 相关。这表明 DP1L1 在这些情况下具有功能作用。因此，DP1L1 可能是结肠癌和 IBD 的诊断和治疗靶点。
