MOLECULAR EPIDEMIOLOGY OF RENAL CANCER

Kidney cancer consists of renal cell cancer (RCC) accounting for over 90 % of all kidney carcinomas and the transitional cell cancer. Clear cell cancer is a predominant type (80–85 %) of RCC. Smoking, overweight, obesity, hypertension, occupational exposures to pesticides, specifically to trichloroethylene are considered causal risk factors for sporadic i.e. non-hereditary RCC. The majority of sporadic RCC have polygenic etiology. They develop as a result of combined effect of large number of low penetrance genetic susceptibility genes (genetic polymorphism). The interplay of exposures to environmental risk factors and genetic susceptibility of exposed individuals is believed to influence the risk of developing sporadic RCC. Inheritance of high penetrance genes is associated with very high risk of the RCC. To these genes belongs, for example, VHL (von Hippel–Lindau). Germline mutations in VHL are causing VHL syndrome and hereditary type of RCC. Risk of RCC in individuals with germ-line mutations is very high however the proportion RCC associated with these events is very low (>5–7 %). Environmental factors virtually do not influence the risk of these cancers.

The studies in molecular epidemiology based on candidate gene approach have shown that certain types (variants) of polymorphisms of GST, MTHFR, TYMS, VHL genes are associated with RCC. The genome wide association studies identified over twenty locus with single nucleotide polymorphism affecting the risk of RCC. The risk loci so far identified for RCC account for only about 10 % of the familial risk of RCC. Thus more studies with larger sample size are needed. As more RCC susceptibility alleles are discovered, deciphering the biological basis of risk variants should provide new insights into the biology of RCC that may lead to new approaches to prevention, early detection and therapeutic intervention.

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