Susceptibility genes related to PCa might function in host immune responses and protection against cell and DNA damage caused by oxidative agents. For example, two suggested susceptibility risk genes for hereditary PCa, RNASEL and MSR1, are both involved with innate immunity. Lymphoblastoid cell lines represent an essential component of the immune response, so this result may indicate that ARLTS1 has a function in immune system processes. Alterations in important molecular pathways involved in PCa have been implicated in proliferative inflammatory atrophy and prostatic intraepithelial neoplasia lesions. Tumor suppressor genes NKX3.1, CDKN1B which encodes p27 and the phosphatase and tensin homologue are highly expressed in normal prostate epithelium and have shown to be down-regulated or absent in PIN and PCa. Since ARLTS1 acts as a tumor suppressor protein and has a decreased expression in PCa, these recent findings are in line with the results from other suggested PCa tumor suppressor proteins. Previously it has been shown that ARLTS1 induces apoptosis in lung cancer cells and in ovarian carcinoma. In the case of prostatic inflammation and antigen engagement, the need for apoptosis increases and the processes of the immune system, together with endogenous inflammatory cells become PD325901 activated. Here we showed that in the lymphoblastoid cell lines of PCa patients, ARLTS1 expression was significantly decreased among the CC carrying patients compared to the wild-type allele T carrying patients. The lymphoblastoid cell lines were derived by Epstein-Barr virus transformation of peripheral mononuclear leucocytes from patients, indicating that these cells have encountered antigen stimuli via viral infection. The CC carrying patients had a low ARLTS1 expression status suggesting that ARLTS1 function is decreased due to this risk genotype and consequently this leads to decreased apoptosis. This may indicate that the Cys148Arg CC genotype contributes to the immune response by diminishing apoptosis rates, decreasing defense mechanisms and finally cancer progression. It has been shown earlier that lung cancer cells carrying the Trp149Stop variant and expressing the truncated protein had a reduced capability to induce apoptosis compared to cells expressing the full-length protein. This reduced apoptosis could also be the causal factor in PCa. Our data suggest for the first time that the predisposing effect of the CC genotype of Cys148Arg is related to reduced expression in immune system cells rather than in tumor cells where ARLTS1 expression is naturally very low. Like all other organs, the normal prostate contains endogenous inflammatory cells and immune response mechanisms. Consequently, the function of ARLTS1 may not exclusively be based on tumor suppression as suggested before, but also on immune response functions that occur either locally in prostate or in peripheral tissues. This is in line with the findings that PCa is a very heterogeneous disease and different mechanisms of cancer progression may occur.