Abstract
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.
Similar content being viewed by others
References
Juhasz F, Boros P, Szegedi G, et al. Immunogenetic and immunologic studies of differentiated thyroid cancer. Cancer 1989;63:1318–26.
Rigopoulou D, Martinez-Laso J, Martinez-Tello F, et al. Both class I and class II HLA antigens are thyroid cancer susceptibility factors. Tissue Antigens 1994;43:281–5.
Wank R, Thomsen C. High risk of squamous cell carcinoma of the cervix for women with HLA-DQW3. Nature 1991;352:723–5.
Barger BO, Acton RT, Soong SJ, Roseman J, Balch C. Increase of HLA-DR4 in melanoma patients from Alabama. Cancer Res 1982;42:4276–9.
Lee JE, Reveille JD, Ross MI, Platsoucas CD. HLA-DQB1*0301 association with increased cutaneous melanoma risk. Int J Cancer 1994;59:510–3.
Kratzik C, Aiginger P, Kuber W, et al. Risk factors for bilateral testicular germ cell tumors. Cancer 1991;68:916–21.
Sory A, Gorski A, Misiuna P, Wallner G, Polkowski W. Is gastric cancer heterogeneity the clue to HLA-DR associated susceptibility? Acta Oncol 1994;33:976–7.
Hilton DA, West KP. An evaluation of the prognostic significance of HLA-DR expression in gastric carcinoma. Cancer 1990;66:1154–7.
Levin VI, Muravskaia GV, Buglova EE, et al. The distribution of HLA-system antigens in lung cancer patients. Vopr Onkol 1991;37:280–3.
Toumbis M, Zervas J, Anagnostopoulou O, et al. HLA antigens and bronchogenic carcinoma in the Greek population. Acta Oncol 1991;30:575–8.
Dawkins RL, Christiansen FT, Kay PH, et al. Disease associations with complotypes, supratypes, and haplotypes. Immunol Rev 1983;70:5–22.
Wingo PA, Tong T, Bolden S. Cancer statistics 1995. CA;1995;45:8–30.
Lynch HT, Watson P, Smyrk TC, et al. Colon cancer genetics. Cancer Suppl 1992;70:1300–12.
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.
Rozen P, Lynch HT, Figer A, et al. Familial colon cancer in the Tel-Aviv area and the influence of ethnic origin. Cancer 1987;60:2355–9.
Burt RW, Bishop DT, Cannon LA, Dowdle MA, Lee RG, Skolnick MH. Dominant inheritance of adenomatous colonic polyps and colorectal cancer. N Engl J Med 1985;312:1540–4.
Cannon-Albright LA, Skolnick MH, Bishop DT, Lee RG, Burt RW. Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med 1988;319:533–7.
Terasaki PI, McClelland JD. Microdroplet assay of human serum cytotoxins. Nature 1964;204:998–1000.
Vartdal F, Gaudernack G, Funderud S, et al. HLA class I and II typing using cells positively selected from blood by immunomagnetic isolation—a fast and reliable technique. Tissue Antigens 1986;28:301–12.
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.
Sakellariou B, Mavroyannis C, Kapellou P, et al. HLA-A,B antigens and colorectal neoplasms [in Greek]. Arch Greek Med 1985;2:138–40.
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.
Lio D, Caccamo N, D'Anna C, et al. Viral antibody titers are influenced by HLA-DR2 phenotype. Exp Clin Immunogenet 1994;11:182–6.
Kaloterakis A, Papasteriades C, Filliotou A, Economidou J, Hadjiyannis S, Stratigos J. HLA in familial and nonfamilial Mediterranean Kaposi's sarcoma in Greece. Tissue Antigens 1995;45:117–9.
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.
Salgame P, Convit J, Bloom BR. Immunological suppression by human CD8+ T cells is receptor dependent and HLA-DQ restricted. Proc Natl Acad Sci USA 1991;88:2598–602.
Author information
Authors and Affiliations
About this article
Cite this article
Chatzipetrou, M.A., Tarassi, K.E., Konstadoulakis, M.M. et al. Human leukocyte antigens as genetic markers in colorectal carcinoma. Dis Colon Rectum 42, 66–70 (1999). https://doi.org/10.1007/BF02235184
Issue Date:
DOI: https://doi.org/10.1007/BF02235184