It has been held for long that genetic factors are responsible for the onset and development of some cancers in human beings. Recent studies have geared to explain the concept from a data-backed point of view giving insight on previously unconsidered options regarding genetics and cancer. The concept of the body’s immune system acting as a protector against invasion from disease-causing antigens has a genetic outlook when considering cancers of the breast, cervical or leukemia and others like testes. The natural body immune surveillance against others is different and weak when faced by tumor cells in the body. The processes that help in maintaining immune surveillance depend on the genetic factor HLA variability and its capability to interact with different types of proteins. This paper will therefore focus on the HLA system and the interrelated interactions in the case of different cancers espousing positive or negative risk factors towards such cancers.
The human leukocyte antigen has two categories, the class I and II types. Until recently, the class I type was held to be the only one responsible for carrying endogenous proteins. New studies however reveal that the class II type also carries the endogenous proteins in the daily function of interaction with the T-cells. In the normal immune body function, T cells are dependent on HLA profiles in the identification of tumor cells for destruction (Amirzagar et al 2007). New studies reveal that histo-compatibility complex (MHC) molecules are present in antigen presentation and the discovery of natural killer inhibitory cells (KIRs) and activatory receptors (KARs). The earlier theorization was that the HLA profile polymorphism can deal with the different mutations of various antigens. However, the non-classical type has little polymorphism thus viral origin antigens like tumors with major histocompatibility complex class have surpassed the immune system (Ruiz-Cabello & Garrido 1998).
It is from this point that tumor escapes notice and destruction therefore the need to enhance the T cells response to tumor antigens by using peptides from proteins that have the capability to be recognized by the cytotoxic T lymphocytes. T cell escape mechanisms are given impetus by changing the phenotypic expression of HLA in different ways either by oncogenic or no oncogenic viruses or by DNA alterations that affect the biosynthetic structure of MHC. In this case, therefore the HLA changes in expressions have changed the landscape in human tumor epidemiology. On the other hand, some tumor tissues lead to the loss of HLA class I. The point of emphasis that arises from here is that tumor cells choose their favorite form of HLA expression (Ruiz-Cabello & Garrido 1998).
The ability to change the HLA expression explains the case in cervical cancer through the presence of hormones and the influence of human papillomavirus which cause downregulation of HLA hence escaping T cell responses. These deletions, insertion and mutations are observed on the cervical lines suggesting loss of heterozygosity (LOH) explaining the presence of a single allele in HLA class I. The switching off of the alleles in HLA class I is a process of alteration that is found in replica in other human cancers. These changes occur in the early development of the cancers and loss of other alleles is a confirmation that tumors choose the defective HLA-tumor zones to cause cancer.
On the other hand tumor cells are destroyed by the NK cells when the HLA class I molecules are absent or are very low. This aids the T cells in ensuring against antigens but the expression of aberrant HLA class I molecules triggers inhibition in NK cells thus they may go undetected. Although the case where cancer takes the aberrant class molecules has not gained enough data evidence to be considered, the need to be careful is essential. The concept of T cells combining with KIRs is important as the specificity of any reaction is controlled by KIRs. This helps to explain that some normal tissues in the body that lack HLA are checked by KIR and thus T cells do not destroy them through the concept of unmasking new tumor targets. This explains that the immune system does not go against self-antigens and avoids autoimmunity which is another helpful way against tumor cells that have escaped CTLs through HLA loss.
With this in mind, therefore, the positive association of the protein P210 kind and CML is crucial in this analysis. The Chronic myelogenous Leukemia (CML) study in Iranian patients espouses that it combines with different alleles in the HLA to cause cancer. However, the absence of positive association may signify that the absence of the allele in certain ethnic groups thus these ethnic groups have a natural immune to Chronic myelogenous Leukemia (CML). In the study of breast cancer the HLA by Isselbacher, (2000) the results revealed no strong negative or positive association with the presented alleles thus the inference was that there was linkage disequilibrium.
This means that breast cancer was not linked to the alterations of HLA hence the negative and positive associations but the presence of possibly resistant alleles and therefore HLA does not matter with the development of breast cancer leaving room for the study of ethnic and other factors like age of the patients. This implies that further studies need to ascertain the presence of peptides in HLA processes in breast cancer-resistant individuals and confirm exactly the relationship between HLA and breast cancer.
With the cervical cancer study conducted by Zoodsma et al, (2005) there was a positive association indicating that cervical cancer is affected by the HLA alteration changes by the tumor cells responsible for cervical neoplasia. The entire HLA region had an association with cancer as the allele found to be in linkage disequilibrium is found in the region. Therefore, the genetic endowment of such an allele in an individual meant that she was at risk of developing cancer. Thus the genetic susceptibility in HLA has positive and negative contributions to human cancers.
In conclusion, therefore, HLA is a factor that must be considered in modern oncology, pathology and immunology health sciences to give insight into the treatment and research on human cancers. The researches conducted left out factors like age, ethnicity and size and did not concern with other genes that appeared to be responsible for some observations as the objective was on HLA and cancer. Therefore, intensive research in the future is required to put these factors into consideration to make sure no stone is left unturned.
References
Amirzagar, A., Khosravi, F., Dianat, S., S., Alimoghadam, K., Ghavamzadeh, F., Ansaripour, B., Moradi, B., & Nikibina, B., 2007. Association of HLA Class II Allele and Haplotype Frequencies with Chronic Myelogenous Leukemia and Age-at-Onset of the Disease. Web.
Isselbacher, K., J, 2000. Genetic susceptibility to breast cancer: HLA DQB*03032 and HLA DRB1*11 may represent protective alleles. Charlestown: Massachusetts General Hospital Cancer Center and Harvard Medical School.
Ruiz-Cabello, F., & Garrido, F., 1998. HLA and cancer: from research to clinical impact. Trends in Immunology, Vol. 19 (12), 539-542.
Zoodsma, M., Nolte, I.,M., Schipper, M., Oosterom, E., Steege Van der, G., E de Vries, E., G., te Meerman, G., J., & J van der Zee, A., G., 2005. Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study. Web.