Chatzipetrou M A, Tarassi K E, Konstadoulakis M M, Pappas H E, Zafirellis K D, Athanassiades T E, Papadopoulos S A, Panousopoulos D G, Golematis B C, Papasteriades C A
First Propaedeutic Surgical Department, University of Athens, Greece.
Dis Colon Rectum. 1999 Jan;42(1):66-70. doi: 10.1007/BF02235184.
Similar to findings obtained for most carcinomas, the pathogenesis of colorectal cancer is considered to be multifactorial. There is strong evidence for an inherited, genetic predisposition to disease in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. There is still debate, however, about the contribution of genetic factors to the pathogenesis of sporadic colorectal cancer. The present study was undertaken to search for human leukocyte antigen associations in a group of patients with colorectal cancer and to correlate the findings with both the histology of the disease and family history.
The allele frequencies of serologically defined human leukocyte antigen class I and II antigens were studied in 101 patients with a recent, histologically confirmed diagnosis of colorectal cancer. All individuals in this study were unrelated to each other. After surgical treatment, all patients were grouped according to the stage (Dukes Stages A, B, C, and D), differentiation (Grades 1, 2, and 3), and the site of the tumor. Patients were also classified with regard to family history for colorectal cancer. The results obtained for human leukocyte antigen frequencies were compared with those of 105 healthy control subjects (control group).
An increased frequency of human leukocyte antigen-B18 (27.72 vs. 14.28 percent; P < 0.025; odds ratio = 2.3) and of human leukocyte antigen-DQ5 (43.56 vs. 22.5 percent; P < 0.01; odds ratio = 2.65) was observed for patients with colorectal cancer vs. control subjects, respectively. In addition, human leukocyte antigen-B18 was present with increased frequency (30.76 percent; P < 0.05; odds ratio = 2.66; and 26.67 percent; P < 0.05; odds ratio = 2.18) among patients with rectal and colon carcinoma, respectively. A higher frequency of human leukocyte antigen-DQ5 (45.33 percent; P < 0.01; odds ratio = 2.84) was observed among patients with colon carcinoma. Remarkably, human leukocyte antigen-DQ5 (50 vs. 22.5 percent; P < 0.05; odds ratio = 3.43) and human leukocyte antigen-A1 (41.66 vs. 12.38 percent; P < 0.01; odds ratio = 5.05) were found to be strongly associated with a family history of colorectal cancer.
The observation of specific human leukocyte antigen associations with particular subsets of colorectal cancer strongly suggests that genetic susceptibility for the development of colorectal cancer exists. Although the multifactorial pathogenesis of colorectal cancer must be considered, human leukocyte antigens may have useful predictive and diagnostic value.
与大多数癌症的研究结果相似，结直肠癌的发病机制被认为是多因素的。有强有力的证据表明，家族性腺瘤性息肉病和遗传性非息肉病性结直肠癌患者存在遗传易感性。然而，关于遗传因素在散发性结直肠癌发病机制中的作用仍存在争议。本研究旨在寻找一组结直肠癌患者中的人类白细胞抗原关联，并将研究结果与疾病的组织学和家族史相关联。
对101例近期经组织学确诊为结直肠癌的患者进行了血清学定义的人类白细胞抗原I类和II类抗原的等位基因频率研究。本研究中的所有个体彼此无关。手术治疗后，所有患者根据分期（杜克分期A、B、C和D）、分化程度（1级、2级和3级）以及肿瘤部位进行分组。患者还根据结直肠癌家族史进行分类。将人类白细胞抗原频率的研究结果与105名健康对照者（对照组）的结果进行比较。
结直肠癌患者与对照者相比，人类白细胞抗原-B18（27.72%对14.28%；P<0.025；比值比=2.3）和人类白细胞抗原-DQ5（43.56%对22.5%；P<0.01；比值比=2.65）的频率分别升高。此外，人类白细胞抗原-B18在直肠癌和结肠癌患者中的频率也分别升高（30.76%；P<0.05；比值比=2.66；和26.67%；P<0.05；比值比=2.18）。结肠癌患者中人类白细胞抗原-DQ5的频率更高（45.33%；P<0.01；比值比=2.84）。值得注意的是，人类白细胞抗原-DQ5（50%对22.5%；P<0.05；比值比=3.43）和人类白细胞抗原-A1（41.66%对12.38%；P<0.01；比值比=5.）与结直肠癌家族史密切相关。
观察到特定的人类白细胞抗原与结直肠癌的特定亚组相关，强烈提示结直肠癌发生存在遗传易感性。尽管必须考虑结直肠癌的多因素发病机制，但人类白细胞抗原可能具有有用的预测和诊断价值。
