Human leukocyte antigens as genetic markers in colorectal carcinoma
- 13 Downloads
PURPOSE: 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. SUBJECTS AND METHODS: 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). RESULTS: An increased frequency of human leukocyte antigen-B18 (27.72vs. 14.28 percent;P<0.025; odds ratio =2.3) and of human leukocyte antigen-DQ5 (43.56vs. 22.5 percent;P<0.01; odds ratio =2.65) was observed for patients with colorectal cancervs. 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 (50vs. 22.5 percent;P<0.05; odds ratio =3.43) and human leukocyte antigen-A1 (41.66vs. 12.38 percent;P<0.01; odds ratio =5.05) were found to be strongly associated with a family history of colorectal cancer. CONCLUSION: 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.
Key wordsColorectal carcinoma Human leukocyte antigens Genetic markers
Unable to display preview. Download preview PDF.
- 11.Dawkins RL, Christiansen FT, Kay PH, et al. Disease associations with complotypes, supratypes, and haplotypes. Immunol Rev 1983;70:5–22.Google Scholar
- 13.Lynch HT, Watson P, Smyrk TC, et al. Colon cancer genetics. Cancer Suppl 1992;70:1300–12.Google Scholar
- 14.Winawer SJ, Enker WE, Levin B. Colorectal cancer. In: Winawer SJ (ed) Management of gastrointestinal diseases. New York: Gower Medical Publishing, 1992;27:1–40.Google Scholar
- 18.Terasaki PI, McClelland JD. Microdroplet assay of human serum cytotoxins. Nature 1964;204:998–1000.Google Scholar
- 20.Yagita A, Abe O, Sekiguchi S. HLA type in patients with colon and rectum cancer and ulcerative colitis with special reference to cancer susceptibility [in Japanese]. Cancer Chemother 1977;4:939–45.Google Scholar
- 21.Sakellariou B, Mavroyannis C, Kapellou P, et al. HLA-A,B antigens and colorectal neoplasms [in Greek]. Arch Greek Med 1985;2:138–40.Google Scholar
- 22.Alcalay M, Bontoux D, Maire PH, Matuchanscky CL, Alcalay D, Tanzen J. HLA-B27 and colorectal cancer. N Engl J Med 1982;307:443–4.Google Scholar
- 25.Papasteriades C, Arseniou P, Bicas N, Ioannides G, Thalassinos N. HLA antigens in Greek type I diabetics. 11th International Histocompatibility Workshop and Conference. Yokohama, Book of Abstracts, Nishimura H, Sasazuki T (eds), Kyushu University, Fukuoka, Japan 1991;167.Google Scholar