Malignancies arise in 20 to 40% of transplant recipients within 20 years of receipt of graft.141 Skin carcinomas account for up to 50% of these cancers. Viruses, including HPVs, Epstein Barr virus and human herpes virus-8 are involved in the pathogenesis of post-transplant tumors, especially skin carcinomas, B-cell lymphomas and Kaposi's sarcoma. Impaired host immune defences, resulting from heavy immunosuppression are also associated with an increased risk of malignancy. Genetic risk factors are also suspected. Accordingly, genetic polymorphisms associated with differential levels of cytokine production may have an important effect on tumorigenesis after organ transplantation. In this context, IL-10 plymorphism is of particular interest, since, in addition to the biological functions of IL-10 discussed in some detail above, ultraviolet-induced DNA damage, a risk factor for skin cancer, also increases production of IL-10.142
For the above reasons, Alamartine et al,84 in a French-based study, investigated possible associations between the IL-10 -1082, -819 and -592 SNPs and the occurrence of post-transplant skin cancers in a series of 70 renal transplant recipients who developed post-transplant squamous (SCC) or basal cell carcinoma (BCC), 70 healthy controls and 70 age, sex and immunosuppression-matched renal recipients without cancer. Taken together, IL-10 -1082, -819, -592 haplotypes were differently distributed when comparing cancer patients with unaffected patients and with controls. Results showed that genotypes associated with low production of IL-10 (IL-10 -1082, -819, -592 GCC negative) were less frequent in cancer patients (23% v 47% in unaffected patients), but only in patients with SCC (12%) and not BCC (37%). In addition, genotypes associated with high IL-10 production (GCC homozygous) were more frequent in cancer patients (24% v 11%), but this difference was significant only when comparing all cancer patients, or patients with SCC, with controls. The frequency of GCC homozygosity was not increased when considering patients with BCC with unaffected patients. The predicted correlation between IL-10 genotype and in vitro secretion of IL-10 by mononuclear cells was also confirmed by the same study.
Therefore results from this study suggest that genetically programmed elevated IL-10 production may favor the development of carcinoma—especially SCC—in renal transplant patients, although, as for most of the studies reviewed in this chapter, this result requires independent confirmation or replication.
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