The influence of genes in cancer development shows different intensities, and it is mediated by diverse mechanisms. It is well known that some cancer types are more linked with the presence of variations in determined genes, such as in breast and ovarian cancer, where the possibility of cancer development is associated with the presence of somatic mutations in BRCA1 or BRAC2 genes. Nevertheless, the link between cancer development and the presence of variations in another genes, like the ones implicated in the immune response, is an additional component that confers an intermediate or a low risk of developing cancer. Despite the vast variability in the relevance of the influence of genes in the pathophysiology and prognosis of the malignant transformation in different cancers, their role should be taken into account. In this regard, polymorphisms in genes involved in the immune response have a relevant role in the shaping of the complex interactions between the immune system and the predisposition, prognosis, and response to treatment of each individual to the development of cancer. Evidence for this is the higher frequency of tumor development in the immunodeficient patients.